CYP2C9 genotypes and diclofenac metabolism in Spanish healthy volunteers

Objective This study analyzed the frequency of CYP2C9 variant alleles and evaluated the impact of CYP2C9 genotype on diclofenac metabolism in a Spanish population. Methods Diclofenac hydroxylation capacity was studied in a population of 102 healthy volunteers. After a single oral dose of 50 mg diclo...
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Autor*in:	Dorado, Pedro [verfasserIn] Berecz, Roland Norberto, Maria-Jesús Yasar, Ümit Dahl, Marja-Liisa LLerena, Adrián

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2003

Schlagwörter:	Diclofenac CYP2C9 Genotyping

Anmerkung:	© Springer-Verlag 2003

Übergeordnetes Werk:	Enthalten in: European journal of clinical pharmacology - Berlin : Springer, 1968, 59(2003), 3 vom: 07. Mai, Seite 221-225
Übergeordnetes Werk:	volume:59 ; year:2003 ; number:3 ; day:07 ; month:05 ; pages:221-225

Links:	Volltext

DOI / URN:	10.1007/s00228-003-0588-0

Katalog-ID:	SPR002564149

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100	1		\|a Dorado, Pedro \|e verfasserin \|4 aut
245	1	0	\|a CYP2C9 genotypes and diclofenac metabolism in Spanish healthy volunteers
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520			\|a Objective This study analyzed the frequency of CYP2C9 variant alleles and evaluated the impact of CYP2C9 genotype on diclofenac metabolism in a Spanish population. Methods Diclofenac hydroxylation capacity was studied in a population of 102 healthy volunteers. After a single oral dose of 50 mg diclofenac the 0- to 8-h urinary concentrations of diclofenac and its main metabolites, 4'-hydroxy (OH), 3′-OH and 5-OH diclofenac were analyzed by high-performance liquid chromatography. CYP2C9 genotyping for the variant alleles CYP2C92 and 3 was carried out with PCR-RFLP. Results The frequencies of CYP2C91, 2, and 3 alleles were 0.74 (95%CI: 0.68–0.80), 0.16 (95%CI: 0.11–0.21) and 0.10 (95%CI: 0.06–0.15), respectively, among the 102 Spaniards studied. The diclofenac/4'-OH diclofenac urinary ratio, but not the diclofenac/3′-OH diclofenac and diclofenac/5-OH diclofenac ratios, was related to CYP2C9 genotype. The diclofenac/4'-OH ratio was significantly higher among subjects with CYP2C91/3 (0.83±0.4, n=14, 95% CI for the difference: 0.02–0.4) and CYP2C92/3 (1.10±0.5, n=4, 95% CI for the difference: 0.16–0.8) genotypes compared to CYP2C91/1 (0.62±0.3, n=59) and approximately threefold higher (1.8) in the only subject homozygous for CYP2C93 variant. Conclusions The frequencies of CYP2C91, 2, and 3 alleles in the Spanish population reported here were similar to those found in the previously studied white European populations, and different of the previously reported in another Spanish population. CYP2C93 allele seems to influence the 4'-hydroxylation of diclofenac, although there is a large overlapping in the urinary metabolic ratio between the genotype groups studied
650		4	\|a Diclofenac \|7 (dpeaa)DE-He213
650		4	\|a CYP2C9 \|7 (dpeaa)DE-He213
650		4	\|a Genotyping \|7 (dpeaa)DE-He213
700	1		\|a Berecz, Roland \|4 aut
700	1		\|a Norberto, Maria-Jesús \|4 aut
700	1		\|a Yasar, Ümit \|4 aut
700	1		\|a Dahl, Marja-Liisa \|4 aut
700	1		\|a LLerena, Adrián \|4 aut
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912			\|a GBV_ILN_105
912			\|a GBV_ILN_110
912			\|a GBV_ILN_120
912			\|a GBV_ILN_138
912			\|a GBV_ILN_150
912			\|a GBV_ILN_151
912			\|a GBV_ILN_152
912			\|a GBV_ILN_161
912			\|a GBV_ILN_170
912			\|a GBV_ILN_171
912			\|a GBV_ILN_187
912			\|a GBV_ILN_213
912			\|a GBV_ILN_224
912			\|a GBV_ILN_230
912			\|a GBV_ILN_250
912			\|a GBV_ILN_267
912			\|a GBV_ILN_281
912			\|a GBV_ILN_285
912			\|a GBV_ILN_293
912			\|a GBV_ILN_370
912			\|a GBV_ILN_602
912			\|a GBV_ILN_636
912			\|a GBV_ILN_702
912			\|a GBV_ILN_711
912			\|a GBV_ILN_2001
912			\|a GBV_ILN_2003
912			\|a GBV_ILN_2004
912			\|a GBV_ILN_2005
912			\|a GBV_ILN_2006
912			\|a GBV_ILN_2007
912			\|a GBV_ILN_2009
912			\|a GBV_ILN_2010
912			\|a GBV_ILN_2011
912			\|a GBV_ILN_2014
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912			\|a GBV_ILN_2025
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912			\|a GBV_ILN_2027
912			\|a GBV_ILN_2031
912			\|a GBV_ILN_2034
912			\|a GBV_ILN_2037
912			\|a GBV_ILN_2038
912			\|a GBV_ILN_2039
912			\|a GBV_ILN_2044
912			\|a GBV_ILN_2048
912			\|a GBV_ILN_2049
912			\|a GBV_ILN_2050
912			\|a GBV_ILN_2055
912			\|a GBV_ILN_2057
912			\|a GBV_ILN_2059
912			\|a GBV_ILN_2061
912			\|a GBV_ILN_2064
912			\|a GBV_ILN_2065
912			\|a GBV_ILN_2068
912			\|a GBV_ILN_2070
912			\|a GBV_ILN_2086
912			\|a GBV_ILN_2088
912			\|a GBV_ILN_2093
912			\|a GBV_ILN_2106
912			\|a GBV_ILN_2107
912			\|a GBV_ILN_2108
912			\|a GBV_ILN_2110
912			\|a GBV_ILN_2111
912			\|a GBV_ILN_2112
912			\|a GBV_ILN_2113
912			\|a GBV_ILN_2116
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912			\|a GBV_ILN_2119
912			\|a GBV_ILN_2122
912			\|a GBV_ILN_2129
912			\|a GBV_ILN_2143
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912			\|a GBV_ILN_2188
912			\|a GBV_ILN_2190
912			\|a GBV_ILN_2232
912			\|a GBV_ILN_2336
912			\|a GBV_ILN_2446
912			\|a GBV_ILN_2470
912			\|a GBV_ILN_2472
912			\|a GBV_ILN_2507
912			\|a GBV_ILN_2522
912			\|a GBV_ILN_2548
912			\|a GBV_ILN_4012
912			\|a GBV_ILN_4035
912			\|a GBV_ILN_4037
912			\|a GBV_ILN_4046
912			\|a GBV_ILN_4112
912			\|a GBV_ILN_4125
912			\|a GBV_ILN_4126
912			\|a GBV_ILN_4242
912			\|a GBV_ILN_4246
912			\|a GBV_ILN_4249
912			\|a GBV_ILN_4251
912			\|a GBV_ILN_4305
912			\|a GBV_ILN_4306
912			\|a GBV_ILN_4307
912			\|a GBV_ILN_4313
912			\|a GBV_ILN_4322
912			\|a GBV_ILN_4323
912			\|a GBV_ILN_4324
912			\|a GBV_ILN_4325
912			\|a GBV_ILN_4326
912			\|a GBV_ILN_4328
912			\|a GBV_ILN_4333
912			\|a GBV_ILN_4334
912			\|a GBV_ILN_4335
912			\|a GBV_ILN_4336
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951			\|a AR
952			\|d 59 \|j 2003 \|e 3 \|b 07 \|c 05 \|h 221-225

Indexfelder

author_variant	p d pd r b rb m j n mjn ü y üy m l d mld a l al
matchkey_str	article:14321041:2003----::y29eoyeadilfnceaoimnpnsh
hierarchy_sort_str	2003
publishDate	2003
allfields	10.1007/s00228-003-0588-0 doi (DE-627)SPR002564149 (SPR)s00228-003-0588-0-e DE-627 ger DE-627 rakwb eng Dorado, Pedro verfasserin aut CYP2C9 genotypes and diclofenac metabolism in Spanish healthy volunteers 2003 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Springer-Verlag 2003 Objective This study analyzed the frequency of CYP2C9 variant alleles and evaluated the impact of CYP2C9 genotype on diclofenac metabolism in a Spanish population. Methods Diclofenac hydroxylation capacity was studied in a population of 102 healthy volunteers. After a single oral dose of 50 mg diclofenac the 0- to 8-h urinary concentrations of diclofenac and its main metabolites, 4'-hydroxy (OH), 3′-OH and 5-OH diclofenac were analyzed by high-performance liquid chromatography. CYP2C9 genotyping for the variant alleles CYP2C92 and 3 was carried out with PCR-RFLP. Results The frequencies of CYP2C91, 2, and 3 alleles were 0.74 (95%CI: 0.68–0.80), 0.16 (95%CI: 0.11–0.21) and 0.10 (95%CI: 0.06–0.15), respectively, among the 102 Spaniards studied. The diclofenac/4'-OH diclofenac urinary ratio, but not the diclofenac/3′-OH diclofenac and diclofenac/5-OH diclofenac ratios, was related to CYP2C9 genotype. The diclofenac/4'-OH ratio was significantly higher among subjects with CYP2C91/3 (0.83±0.4, n=14, 95% CI for the difference: 0.02–0.4) and CYP2C92/3 (1.10±0.5, n=4, 95% CI for the difference: 0.16–0.8) genotypes compared to CYP2C91/1 (0.62±0.3, n=59) and approximately threefold higher (1.8) in the only subject homozygous for CYP2C93 variant. Conclusions The frequencies of CYP2C91, 2, and 3 alleles in the Spanish population reported here were similar to those found in the previously studied white European populations, and different of the previously reported in another Spanish population. CYP2C93 allele seems to influence the 4'-hydroxylation of diclofenac, although there is a large overlapping in the urinary metabolic ratio between the genotype groups studied Diclofenac (dpeaa)DE-He213 CYP2C9 (dpeaa)DE-He213 Genotyping (dpeaa)DE-He213 Berecz, Roland aut Norberto, Maria-Jesús aut Yasar, Ümit aut Dahl, Marja-Liisa aut LLerena, Adrián aut Enthalten in European journal of clinical pharmacology Berlin : Springer, 1968 59(2003), 3 vom: 07. Mai, Seite 221-225 (DE-627)253722829 (DE-600)1459058-X 1432-1041 nnns volume:59 year:2003 number:3 day:07 month:05 pages:221-225 https://dx.doi.org/10.1007/s00228-003-0588-0 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_267 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_711 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 59 2003 3 07 05 221-225
spelling	10.1007/s00228-003-0588-0 doi (DE-627)SPR002564149 (SPR)s00228-003-0588-0-e DE-627 ger DE-627 rakwb eng Dorado, Pedro verfasserin aut CYP2C9 genotypes and diclofenac metabolism in Spanish healthy volunteers 2003 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Springer-Verlag 2003 Objective This study analyzed the frequency of CYP2C9 variant alleles and evaluated the impact of CYP2C9 genotype on diclofenac metabolism in a Spanish population. Methods Diclofenac hydroxylation capacity was studied in a population of 102 healthy volunteers. After a single oral dose of 50 mg diclofenac the 0- to 8-h urinary concentrations of diclofenac and its main metabolites, 4'-hydroxy (OH), 3′-OH and 5-OH diclofenac were analyzed by high-performance liquid chromatography. CYP2C9 genotyping for the variant alleles CYP2C92 and 3 was carried out with PCR-RFLP. Results The frequencies of CYP2C91, 2, and 3 alleles were 0.74 (95%CI: 0.68–0.80), 0.16 (95%CI: 0.11–0.21) and 0.10 (95%CI: 0.06–0.15), respectively, among the 102 Spaniards studied. The diclofenac/4'-OH diclofenac urinary ratio, but not the diclofenac/3′-OH diclofenac and diclofenac/5-OH diclofenac ratios, was related to CYP2C9 genotype. The diclofenac/4'-OH ratio was significantly higher among subjects with CYP2C91/3 (0.83±0.4, n=14, 95% CI for the difference: 0.02–0.4) and CYP2C92/3 (1.10±0.5, n=4, 95% CI for the difference: 0.16–0.8) genotypes compared to CYP2C91/1 (0.62±0.3, n=59) and approximately threefold higher (1.8) in the only subject homozygous for CYP2C93 variant. Conclusions The frequencies of CYP2C91, 2, and 3 alleles in the Spanish population reported here were similar to those found in the previously studied white European populations, and different of the previously reported in another Spanish population. CYP2C93 allele seems to influence the 4'-hydroxylation of diclofenac, although there is a large overlapping in the urinary metabolic ratio between the genotype groups studied Diclofenac (dpeaa)DE-He213 CYP2C9 (dpeaa)DE-He213 Genotyping (dpeaa)DE-He213 Berecz, Roland aut Norberto, Maria-Jesús aut Yasar, Ümit aut Dahl, Marja-Liisa aut LLerena, Adrián aut Enthalten in European journal of clinical pharmacology Berlin : Springer, 1968 59(2003), 3 vom: 07. Mai, Seite 221-225 (DE-627)253722829 (DE-600)1459058-X 1432-1041 nnns volume:59 year:2003 number:3 day:07 month:05 pages:221-225 https://dx.doi.org/10.1007/s00228-003-0588-0 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_267 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_711 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 59 2003 3 07 05 221-225
allfields_unstemmed	10.1007/s00228-003-0588-0 doi (DE-627)SPR002564149 (SPR)s00228-003-0588-0-e DE-627 ger DE-627 rakwb eng Dorado, Pedro verfasserin aut CYP2C9 genotypes and diclofenac metabolism in Spanish healthy volunteers 2003 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Springer-Verlag 2003 Objective This study analyzed the frequency of CYP2C9 variant alleles and evaluated the impact of CYP2C9 genotype on diclofenac metabolism in a Spanish population. Methods Diclofenac hydroxylation capacity was studied in a population of 102 healthy volunteers. After a single oral dose of 50 mg diclofenac the 0- to 8-h urinary concentrations of diclofenac and its main metabolites, 4'-hydroxy (OH), 3′-OH and 5-OH diclofenac were analyzed by high-performance liquid chromatography. CYP2C9 genotyping for the variant alleles CYP2C92 and 3 was carried out with PCR-RFLP. Results The frequencies of CYP2C91, 2, and 3 alleles were 0.74 (95%CI: 0.68–0.80), 0.16 (95%CI: 0.11–0.21) and 0.10 (95%CI: 0.06–0.15), respectively, among the 102 Spaniards studied. The diclofenac/4'-OH diclofenac urinary ratio, but not the diclofenac/3′-OH diclofenac and diclofenac/5-OH diclofenac ratios, was related to CYP2C9 genotype. The diclofenac/4'-OH ratio was significantly higher among subjects with CYP2C91/3 (0.83±0.4, n=14, 95% CI for the difference: 0.02–0.4) and CYP2C92/3 (1.10±0.5, n=4, 95% CI for the difference: 0.16–0.8) genotypes compared to CYP2C91/1 (0.62±0.3, n=59) and approximately threefold higher (1.8) in the only subject homozygous for CYP2C93 variant. Conclusions The frequencies of CYP2C91, 2, and 3 alleles in the Spanish population reported here were similar to those found in the previously studied white European populations, and different of the previously reported in another Spanish population. CYP2C93 allele seems to influence the 4'-hydroxylation of diclofenac, although there is a large overlapping in the urinary metabolic ratio between the genotype groups studied Diclofenac (dpeaa)DE-He213 CYP2C9 (dpeaa)DE-He213 Genotyping (dpeaa)DE-He213 Berecz, Roland aut Norberto, Maria-Jesús aut Yasar, Ümit aut Dahl, Marja-Liisa aut LLerena, Adrián aut Enthalten in European journal of clinical pharmacology Berlin : Springer, 1968 59(2003), 3 vom: 07. Mai, Seite 221-225 (DE-627)253722829 (DE-600)1459058-X 1432-1041 nnns volume:59 year:2003 number:3 day:07 month:05 pages:221-225 https://dx.doi.org/10.1007/s00228-003-0588-0 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_267 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_711 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 59 2003 3 07 05 221-225
allfieldsGer	10.1007/s00228-003-0588-0 doi (DE-627)SPR002564149 (SPR)s00228-003-0588-0-e DE-627 ger DE-627 rakwb eng Dorado, Pedro verfasserin aut CYP2C9 genotypes and diclofenac metabolism in Spanish healthy volunteers 2003 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Springer-Verlag 2003 Objective This study analyzed the frequency of CYP2C9 variant alleles and evaluated the impact of CYP2C9 genotype on diclofenac metabolism in a Spanish population. Methods Diclofenac hydroxylation capacity was studied in a population of 102 healthy volunteers. After a single oral dose of 50 mg diclofenac the 0- to 8-h urinary concentrations of diclofenac and its main metabolites, 4'-hydroxy (OH), 3′-OH and 5-OH diclofenac were analyzed by high-performance liquid chromatography. CYP2C9 genotyping for the variant alleles CYP2C92 and 3 was carried out with PCR-RFLP. Results The frequencies of CYP2C91, 2, and 3 alleles were 0.74 (95%CI: 0.68–0.80), 0.16 (95%CI: 0.11–0.21) and 0.10 (95%CI: 0.06–0.15), respectively, among the 102 Spaniards studied. The diclofenac/4'-OH diclofenac urinary ratio, but not the diclofenac/3′-OH diclofenac and diclofenac/5-OH diclofenac ratios, was related to CYP2C9 genotype. The diclofenac/4'-OH ratio was significantly higher among subjects with CYP2C91/3 (0.83±0.4, n=14, 95% CI for the difference: 0.02–0.4) and CYP2C92/3 (1.10±0.5, n=4, 95% CI for the difference: 0.16–0.8) genotypes compared to CYP2C91/1 (0.62±0.3, n=59) and approximately threefold higher (1.8) in the only subject homozygous for CYP2C93 variant. Conclusions The frequencies of CYP2C91, 2, and 3 alleles in the Spanish population reported here were similar to those found in the previously studied white European populations, and different of the previously reported in another Spanish population. CYP2C93 allele seems to influence the 4'-hydroxylation of diclofenac, although there is a large overlapping in the urinary metabolic ratio between the genotype groups studied Diclofenac (dpeaa)DE-He213 CYP2C9 (dpeaa)DE-He213 Genotyping (dpeaa)DE-He213 Berecz, Roland aut Norberto, Maria-Jesús aut Yasar, Ümit aut Dahl, Marja-Liisa aut LLerena, Adrián aut Enthalten in European journal of clinical pharmacology Berlin : Springer, 1968 59(2003), 3 vom: 07. Mai, Seite 221-225 (DE-627)253722829 (DE-600)1459058-X 1432-1041 nnns volume:59 year:2003 number:3 day:07 month:05 pages:221-225 https://dx.doi.org/10.1007/s00228-003-0588-0 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_267 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_711 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 59 2003 3 07 05 221-225
allfieldsSound	10.1007/s00228-003-0588-0 doi (DE-627)SPR002564149 (SPR)s00228-003-0588-0-e DE-627 ger DE-627 rakwb eng Dorado, Pedro verfasserin aut CYP2C9 genotypes and diclofenac metabolism in Spanish healthy volunteers 2003 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Springer-Verlag 2003 Objective This study analyzed the frequency of CYP2C9 variant alleles and evaluated the impact of CYP2C9 genotype on diclofenac metabolism in a Spanish population. Methods Diclofenac hydroxylation capacity was studied in a population of 102 healthy volunteers. After a single oral dose of 50 mg diclofenac the 0- to 8-h urinary concentrations of diclofenac and its main metabolites, 4'-hydroxy (OH), 3′-OH and 5-OH diclofenac were analyzed by high-performance liquid chromatography. CYP2C9 genotyping for the variant alleles CYP2C92 and 3 was carried out with PCR-RFLP. Results The frequencies of CYP2C91, 2, and 3 alleles were 0.74 (95%CI: 0.68–0.80), 0.16 (95%CI: 0.11–0.21) and 0.10 (95%CI: 0.06–0.15), respectively, among the 102 Spaniards studied. The diclofenac/4'-OH diclofenac urinary ratio, but not the diclofenac/3′-OH diclofenac and diclofenac/5-OH diclofenac ratios, was related to CYP2C9 genotype. The diclofenac/4'-OH ratio was significantly higher among subjects with CYP2C91/3 (0.83±0.4, n=14, 95% CI for the difference: 0.02–0.4) and CYP2C92/3 (1.10±0.5, n=4, 95% CI for the difference: 0.16–0.8) genotypes compared to CYP2C91/1 (0.62±0.3, n=59) and approximately threefold higher (1.8) in the only subject homozygous for CYP2C93 variant. Conclusions The frequencies of CYP2C91, 2, and 3 alleles in the Spanish population reported here were similar to those found in the previously studied white European populations, and different of the previously reported in another Spanish population. CYP2C93 allele seems to influence the 4'-hydroxylation of diclofenac, although there is a large overlapping in the urinary metabolic ratio between the genotype groups studied Diclofenac (dpeaa)DE-He213 CYP2C9 (dpeaa)DE-He213 Genotyping (dpeaa)DE-He213 Berecz, Roland aut Norberto, Maria-Jesús aut Yasar, Ümit aut Dahl, Marja-Liisa aut LLerena, Adrián aut Enthalten in European journal of clinical pharmacology Berlin : Springer, 1968 59(2003), 3 vom: 07. Mai, Seite 221-225 (DE-627)253722829 (DE-600)1459058-X 1432-1041 nnns volume:59 year:2003 number:3 day:07 month:05 pages:221-225 https://dx.doi.org/10.1007/s00228-003-0588-0 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_267 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_711 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 59 2003 3 07 05 221-225
language	English
source	Enthalten in European journal of clinical pharmacology 59(2003), 3 vom: 07. Mai, Seite 221-225 volume:59 year:2003 number:3 day:07 month:05 pages:221-225
sourceStr	Enthalten in European journal of clinical pharmacology 59(2003), 3 vom: 07. Mai, Seite 221-225 volume:59 year:2003 number:3 day:07 month:05 pages:221-225
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	Diclofenac CYP2C9 Genotyping
isfreeaccess_bool	false
container_title	European journal of clinical pharmacology
authorswithroles_txt_mv	Dorado, Pedro @@aut@@ Berecz, Roland @@aut@@ Norberto, Maria-Jesús @@aut@@ Yasar, Ümit @@aut@@ Dahl, Marja-Liisa @@aut@@ LLerena, Adrián @@aut@@
publishDateDaySort_date	2003-05-07T00:00:00Z
hierarchy_top_id	253722829
id	SPR002564149
language_de	englisch
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Methods Diclofenac hydroxylation capacity was studied in a population of 102 healthy volunteers. After a single oral dose of 50 mg diclofenac the 0- to 8-h urinary concentrations of diclofenac and its main metabolites, 4'-hydroxy (OH), 3′-OH and 5-OH diclofenac were analyzed by high-performance liquid chromatography. CYP2C9 genotyping for the variant alleles CYP2C92 and 3 was carried out with PCR-RFLP. Results The frequencies of CYP2C91, 2, and 3 alleles were 0.74 (95%CI: 0.68–0.80), 0.16 (95%CI: 0.11–0.21) and 0.10 (95%CI: 0.06–0.15), respectively, among the 102 Spaniards studied. The diclofenac/4'-OH diclofenac urinary ratio, but not the diclofenac/3′-OH diclofenac and diclofenac/5-OH diclofenac ratios, was related to CYP2C9 genotype. The diclofenac/4'-OH ratio was significantly higher among subjects with CYP2C91/3 (0.83±0.4, n=14, 95% CI for the difference: 0.02–0.4) and CYP2C92/3 (1.10±0.5, n=4, 95% CI for the difference: 0.16–0.8) genotypes compared to CYP2C91/1 (0.62±0.3, n=59) and approximately threefold higher (1.8) in the only subject homozygous for CYP2C93 variant. Conclusions The frequencies of CYP2C91, 2, and 3 alleles in the Spanish population reported here were similar to those found in the previously studied white European populations, and different of the previously reported in another Spanish population. 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author	Dorado, Pedro
spellingShingle	Dorado, Pedro misc Diclofenac misc CYP2C9 misc Genotyping CYP2C9 genotypes and diclofenac metabolism in Spanish healthy volunteers
authorStr	Dorado, Pedro
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topic_title	CYP2C9 genotypes and diclofenac metabolism in Spanish healthy volunteers Diclofenac (dpeaa)DE-He213 CYP2C9 (dpeaa)DE-He213 Genotyping (dpeaa)DE-He213
topic	misc Diclofenac misc CYP2C9 misc Genotyping
topic_unstemmed	misc Diclofenac misc CYP2C9 misc Genotyping
topic_browse	misc Diclofenac misc CYP2C9 misc Genotyping
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title	CYP2C9 genotypes and diclofenac metabolism in Spanish healthy volunteers
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title_full	CYP2C9 genotypes and diclofenac metabolism in Spanish healthy volunteers
author_sort	Dorado, Pedro
journal	European journal of clinical pharmacology
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author_browse	Dorado, Pedro Berecz, Roland Norberto, Maria-Jesús Yasar, Ümit Dahl, Marja-Liisa LLerena, Adrián
container_volume	59
format_se	Elektronische Aufsätze
author-letter	Dorado, Pedro
doi_str_mv	10.1007/s00228-003-0588-0
title_sort	cyp2c9 genotypes and diclofenac metabolism in spanish healthy volunteers
title_auth	CYP2C9 genotypes and diclofenac metabolism in Spanish healthy volunteers
abstract	Objective This study analyzed the frequency of CYP2C9 variant alleles and evaluated the impact of CYP2C9 genotype on diclofenac metabolism in a Spanish population. Methods Diclofenac hydroxylation capacity was studied in a population of 102 healthy volunteers. After a single oral dose of 50 mg diclofenac the 0- to 8-h urinary concentrations of diclofenac and its main metabolites, 4'-hydroxy (OH), 3′-OH and 5-OH diclofenac were analyzed by high-performance liquid chromatography. CYP2C9 genotyping for the variant alleles CYP2C92 and 3 was carried out with PCR-RFLP. Results The frequencies of CYP2C91, 2, and 3 alleles were 0.74 (95%CI: 0.68–0.80), 0.16 (95%CI: 0.11–0.21) and 0.10 (95%CI: 0.06–0.15), respectively, among the 102 Spaniards studied. The diclofenac/4'-OH diclofenac urinary ratio, but not the diclofenac/3′-OH diclofenac and diclofenac/5-OH diclofenac ratios, was related to CYP2C9 genotype. The diclofenac/4'-OH ratio was significantly higher among subjects with CYP2C91/3 (0.83±0.4, n=14, 95% CI for the difference: 0.02–0.4) and CYP2C92/3 (1.10±0.5, n=4, 95% CI for the difference: 0.16–0.8) genotypes compared to CYP2C91/1 (0.62±0.3, n=59) and approximately threefold higher (1.8) in the only subject homozygous for CYP2C93 variant. Conclusions The frequencies of CYP2C91, 2, and 3 alleles in the Spanish population reported here were similar to those found in the previously studied white European populations, and different of the previously reported in another Spanish population. CYP2C93 allele seems to influence the 4'-hydroxylation of diclofenac, although there is a large overlapping in the urinary metabolic ratio between the genotype groups studied © Springer-Verlag 2003
abstractGer	Objective This study analyzed the frequency of CYP2C9 variant alleles and evaluated the impact of CYP2C9 genotype on diclofenac metabolism in a Spanish population. Methods Diclofenac hydroxylation capacity was studied in a population of 102 healthy volunteers. After a single oral dose of 50 mg diclofenac the 0- to 8-h urinary concentrations of diclofenac and its main metabolites, 4'-hydroxy (OH), 3′-OH and 5-OH diclofenac were analyzed by high-performance liquid chromatography. CYP2C9 genotyping for the variant alleles CYP2C92 and 3 was carried out with PCR-RFLP. Results The frequencies of CYP2C91, 2, and 3 alleles were 0.74 (95%CI: 0.68–0.80), 0.16 (95%CI: 0.11–0.21) and 0.10 (95%CI: 0.06–0.15), respectively, among the 102 Spaniards studied. The diclofenac/4'-OH diclofenac urinary ratio, but not the diclofenac/3′-OH diclofenac and diclofenac/5-OH diclofenac ratios, was related to CYP2C9 genotype. The diclofenac/4'-OH ratio was significantly higher among subjects with CYP2C91/3 (0.83±0.4, n=14, 95% CI for the difference: 0.02–0.4) and CYP2C92/3 (1.10±0.5, n=4, 95% CI for the difference: 0.16–0.8) genotypes compared to CYP2C91/1 (0.62±0.3, n=59) and approximately threefold higher (1.8) in the only subject homozygous for CYP2C93 variant. Conclusions The frequencies of CYP2C91, 2, and 3 alleles in the Spanish population reported here were similar to those found in the previously studied white European populations, and different of the previously reported in another Spanish population. CYP2C93 allele seems to influence the 4'-hydroxylation of diclofenac, although there is a large overlapping in the urinary metabolic ratio between the genotype groups studied © Springer-Verlag 2003
abstract_unstemmed	Objective This study analyzed the frequency of CYP2C9 variant alleles and evaluated the impact of CYP2C9 genotype on diclofenac metabolism in a Spanish population. Methods Diclofenac hydroxylation capacity was studied in a population of 102 healthy volunteers. After a single oral dose of 50 mg diclofenac the 0- to 8-h urinary concentrations of diclofenac and its main metabolites, 4'-hydroxy (OH), 3′-OH and 5-OH diclofenac were analyzed by high-performance liquid chromatography. CYP2C9 genotyping for the variant alleles CYP2C92 and 3 was carried out with PCR-RFLP. Results The frequencies of CYP2C91, 2, and 3 alleles were 0.74 (95%CI: 0.68–0.80), 0.16 (95%CI: 0.11–0.21) and 0.10 (95%CI: 0.06–0.15), respectively, among the 102 Spaniards studied. The diclofenac/4'-OH diclofenac urinary ratio, but not the diclofenac/3′-OH diclofenac and diclofenac/5-OH diclofenac ratios, was related to CYP2C9 genotype. The diclofenac/4'-OH ratio was significantly higher among subjects with CYP2C91/3 (0.83±0.4, n=14, 95% CI for the difference: 0.02–0.4) and CYP2C92/3 (1.10±0.5, n=4, 95% CI for the difference: 0.16–0.8) genotypes compared to CYP2C91/1 (0.62±0.3, n=59) and approximately threefold higher (1.8) in the only subject homozygous for CYP2C93 variant. Conclusions The frequencies of CYP2C91, 2, and 3 alleles in the Spanish population reported here were similar to those found in the previously studied white European populations, and different of the previously reported in another Spanish population. CYP2C93 allele seems to influence the 4'-hydroxylation of diclofenac, although there is a large overlapping in the urinary metabolic ratio between the genotype groups studied © Springer-Verlag 2003
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container_issue	3
title_short	CYP2C9 genotypes and diclofenac metabolism in Spanish healthy volunteers
url	https://dx.doi.org/10.1007/s00228-003-0588-0
remote_bool	true
author2	Berecz, Roland Norberto, Maria-Jesús Yasar, Ümit Dahl, Marja-Liisa LLerena, Adrián
author2Str	Berecz, Roland Norberto, Maria-Jesús Yasar, Ümit Dahl, Marja-Liisa LLerena, Adrián
ppnlink	253722829
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doi_str	10.1007/s00228-003-0588-0
up_date	2024-07-03T13:46:42.438Z
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Methods Diclofenac hydroxylation capacity was studied in a population of 102 healthy volunteers. After a single oral dose of 50 mg diclofenac the 0- to 8-h urinary concentrations of diclofenac and its main metabolites, 4'-hydroxy (OH), 3′-OH and 5-OH diclofenac were analyzed by high-performance liquid chromatography. CYP2C9 genotyping for the variant alleles CYP2C92 and 3 was carried out with PCR-RFLP. Results The frequencies of CYP2C91, 2, and 3 alleles were 0.74 (95%CI: 0.68–0.80), 0.16 (95%CI: 0.11–0.21) and 0.10 (95%CI: 0.06–0.15), respectively, among the 102 Spaniards studied. The diclofenac/4'-OH diclofenac urinary ratio, but not the diclofenac/3′-OH diclofenac and diclofenac/5-OH diclofenac ratios, was related to CYP2C9 genotype. 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CYP2C9 genotypes and diclofenac metabolism in Spanish healthy volunteers

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