Influence of primaquine and ritonavir interaction on CYP3A4 mRNA expression in HepG2 cell culture

<p<<strong<Background:</strong< Concomitant treatment with antimalaria and antiretroviral drug is a new challenge in the management of malaria and HIV co-infection. Primaquine is a substrate and also an inhibitor of CYP3A4, while ritonavir is a substrate, an inhibitor, and also an...
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Autor*in:	Adam Iskandarmudasyah [verfasserIn] Melva Louisa [verfasserIn] Arleni Arleni [verfasserIn] Sri W.A. Jusman [verfasserIn] Franciscus D. Suyatna [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2012

Übergeordnetes Werk:	In: Medical Journal of Indonesia - Faculty of Medicine Universitas Indonesia, 2013, 21(2012), 1, Seite 3-7
Übergeordnetes Werk:	volume:21 ; year:2012 ; number:1 ; pages:3-7

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc Journal toc

DOI / URN:	10.13181/mji.v21i1.471

Katalog-ID:	DOAJ050833960

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245	1	0	\|a Influence of primaquine and ritonavir interaction on CYP3A4 mRNA expression in HepG2 cell culture
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520			\|a <p<<strong<Background:</strong< Concomitant treatment with antimalaria and antiretroviral drug is a new challenge in the management of malaria and HIV co-infection. Primaquine is a substrate and also an inhibitor of CYP3A4, while ritonavir is a substrate, an inhibitor, and also an inducer for CYP3A4. The objective of this study is to measure the CYP3A4 mRNA expression in HepG2 cell culture induced by primaquine and ritonavir co-treatment.</p<<p<<strong<Methods:</strong< For the initial study HepG2 cells were treated with 30, 40, 50 uM of primaquine; 2, 10, 20 uM ritonavir; DMSO ≤0.1 % for negative control; or 20 uM rifampicin for positive control. While for the co-treatment study the cells were treated with 40 uM primaquine+10 uM ritonavir; DMSO ≤0.1 %; or 20 uM rifampicin for 72 hours. The cells were harvested using trypsin–EDTA and total RNA was extracted using the Tripure isolation reagent. After determining the quantity of RNA spectrophotometrically, CYP3A4 mRNA expression was quantified using real-time reverse transcription polymerase chain reaction (RT-PCR).</p<<p<<strong<Results:</strong< The expression of CYP3A4 mRNA was up-regulated (1.22 fold over control) in HepG2 cells co-treated with primaquine and ritonavir. These data suggest that the induction effect of ritonavir was more dominant than the inhibitory effect of primaquine.</p<<p<<strong<Conclusion:</strong< Concomitant administration of primaquine and ritonavir result in up-regulation of CYP3A4 mRNA expression in vitro. <em<<strong<(Med J Indones 2012;21:3-7)</strong<</em<</p<<p<<strong<Keywords:</strong< <em<CYP450 induction, CYP3A4, drug interaction, primaquine, ritonavir</em<</p<
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700	0		\|a Franciscus D. Suyatna \|e verfasserin \|4 aut
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allfields	10.13181/mji.v21i1.471 doi (DE-627)DOAJ050833960 (DE-599)DOAJe03079fa98d34319a3aa17afd94d394b DE-627 ger DE-627 rakwb eng R5-920 Adam Iskandarmudasyah verfasserin aut Influence of primaquine and ritonavir interaction on CYP3A4 mRNA expression in HepG2 cell culture 2012 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier <p<<strong<Background:</strong< Concomitant treatment with antimalaria and antiretroviral drug is a new challenge in the management of malaria and HIV co-infection. Primaquine is a substrate and also an inhibitor of CYP3A4, while ritonavir is a substrate, an inhibitor, and also an inducer for CYP3A4. The objective of this study is to measure the CYP3A4 mRNA expression in HepG2 cell culture induced by primaquine and ritonavir co-treatment.</p<<p<<strong<Methods:</strong< For the initial study HepG2 cells were treated with 30, 40, 50 uM of primaquine; 2, 10, 20 uM ritonavir; DMSO ≤0.1 % for negative control; or 20 uM rifampicin for positive control. While for the co-treatment study the cells were treated with 40 uM primaquine+10 uM ritonavir; DMSO ≤0.1 %; or 20 uM rifampicin for 72 hours. The cells were harvested using trypsin–EDTA and total RNA was extracted using the Tripure isolation reagent. After determining the quantity of RNA spectrophotometrically, CYP3A4 mRNA expression was quantified using real-time reverse transcription polymerase chain reaction (RT-PCR).</p<<p<<strong<Results:</strong< The expression of CYP3A4 mRNA was up-regulated (1.22 fold over control) in HepG2 cells co-treated with primaquine and ritonavir. These data suggest that the induction effect of ritonavir was more dominant than the inhibitory effect of primaquine.</p<<p<<strong<Conclusion:</strong< Concomitant administration of primaquine and ritonavir result in up-regulation of CYP3A4 mRNA expression in vitro. <em<<strong<(Med J Indones 2012;21:3-7)</strong<</em<</p<<p<<strong<Keywords:</strong< <em<CYP450 induction, CYP3A4, drug interaction, primaquine, ritonavir</em<</p< Medicine (General) Melva Louisa verfasserin aut Arleni Arleni verfasserin aut Sri W.A. Jusman verfasserin aut Franciscus D. Suyatna verfasserin aut In Medical Journal of Indonesia Faculty of Medicine Universitas Indonesia, 2013 21(2012), 1, Seite 3-7 (DE-627)747137862 (DE-600)2716886-4 22528083 nnns volume:21 year:2012 number:1 pages:3-7 https://doi.org/10.13181/mji.v21i1.471 kostenfrei https://doaj.org/article/e03079fa98d34319a3aa17afd94d394b kostenfrei http://mji.ui.ac.id/journal/index.php/mji/article/view/471 kostenfrei https://doaj.org/toc/0853-1773 Journal toc kostenfrei https://doaj.org/toc/2252-8083 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 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_4338 GBV_ILN_4367 GBV_ILN_4700 AR 21 2012 1 3-7
spelling	10.13181/mji.v21i1.471 doi (DE-627)DOAJ050833960 (DE-599)DOAJe03079fa98d34319a3aa17afd94d394b DE-627 ger DE-627 rakwb eng R5-920 Adam Iskandarmudasyah verfasserin aut Influence of primaquine and ritonavir interaction on CYP3A4 mRNA expression in HepG2 cell culture 2012 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier <p<<strong<Background:</strong< Concomitant treatment with antimalaria and antiretroviral drug is a new challenge in the management of malaria and HIV co-infection. Primaquine is a substrate and also an inhibitor of CYP3A4, while ritonavir is a substrate, an inhibitor, and also an inducer for CYP3A4. The objective of this study is to measure the CYP3A4 mRNA expression in HepG2 cell culture induced by primaquine and ritonavir co-treatment.</p<<p<<strong<Methods:</strong< For the initial study HepG2 cells were treated with 30, 40, 50 uM of primaquine; 2, 10, 20 uM ritonavir; DMSO ≤0.1 % for negative control; or 20 uM rifampicin for positive control. While for the co-treatment study the cells were treated with 40 uM primaquine+10 uM ritonavir; DMSO ≤0.1 %; or 20 uM rifampicin for 72 hours. The cells were harvested using trypsin–EDTA and total RNA was extracted using the Tripure isolation reagent. After determining the quantity of RNA spectrophotometrically, CYP3A4 mRNA expression was quantified using real-time reverse transcription polymerase chain reaction (RT-PCR).</p<<p<<strong<Results:</strong< The expression of CYP3A4 mRNA was up-regulated (1.22 fold over control) in HepG2 cells co-treated with primaquine and ritonavir. These data suggest that the induction effect of ritonavir was more dominant than the inhibitory effect of primaquine.</p<<p<<strong<Conclusion:</strong< Concomitant administration of primaquine and ritonavir result in up-regulation of CYP3A4 mRNA expression in vitro. <em<<strong<(Med J Indones 2012;21:3-7)</strong<</em<</p<<p<<strong<Keywords:</strong< <em<CYP450 induction, CYP3A4, drug interaction, primaquine, ritonavir</em<</p< Medicine (General) Melva Louisa verfasserin aut Arleni Arleni verfasserin aut Sri W.A. Jusman verfasserin aut Franciscus D. Suyatna verfasserin aut In Medical Journal of Indonesia Faculty of Medicine Universitas Indonesia, 2013 21(2012), 1, Seite 3-7 (DE-627)747137862 (DE-600)2716886-4 22528083 nnns volume:21 year:2012 number:1 pages:3-7 https://doi.org/10.13181/mji.v21i1.471 kostenfrei https://doaj.org/article/e03079fa98d34319a3aa17afd94d394b kostenfrei http://mji.ui.ac.id/journal/index.php/mji/article/view/471 kostenfrei https://doaj.org/toc/0853-1773 Journal toc kostenfrei https://doaj.org/toc/2252-8083 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 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_4338 GBV_ILN_4367 GBV_ILN_4700 AR 21 2012 1 3-7
allfields_unstemmed	10.13181/mji.v21i1.471 doi (DE-627)DOAJ050833960 (DE-599)DOAJe03079fa98d34319a3aa17afd94d394b DE-627 ger DE-627 rakwb eng R5-920 Adam Iskandarmudasyah verfasserin aut Influence of primaquine and ritonavir interaction on CYP3A4 mRNA expression in HepG2 cell culture 2012 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier <p<<strong<Background:</strong< Concomitant treatment with antimalaria and antiretroviral drug is a new challenge in the management of malaria and HIV co-infection. Primaquine is a substrate and also an inhibitor of CYP3A4, while ritonavir is a substrate, an inhibitor, and also an inducer for CYP3A4. The objective of this study is to measure the CYP3A4 mRNA expression in HepG2 cell culture induced by primaquine and ritonavir co-treatment.</p<<p<<strong<Methods:</strong< For the initial study HepG2 cells were treated with 30, 40, 50 uM of primaquine; 2, 10, 20 uM ritonavir; DMSO ≤0.1 % for negative control; or 20 uM rifampicin for positive control. While for the co-treatment study the cells were treated with 40 uM primaquine+10 uM ritonavir; DMSO ≤0.1 %; or 20 uM rifampicin for 72 hours. The cells were harvested using trypsin–EDTA and total RNA was extracted using the Tripure isolation reagent. After determining the quantity of RNA spectrophotometrically, CYP3A4 mRNA expression was quantified using real-time reverse transcription polymerase chain reaction (RT-PCR).</p<<p<<strong<Results:</strong< The expression of CYP3A4 mRNA was up-regulated (1.22 fold over control) in HepG2 cells co-treated with primaquine and ritonavir. These data suggest that the induction effect of ritonavir was more dominant than the inhibitory effect of primaquine.</p<<p<<strong<Conclusion:</strong< Concomitant administration of primaquine and ritonavir result in up-regulation of CYP3A4 mRNA expression in vitro. <em<<strong<(Med J Indones 2012;21:3-7)</strong<</em<</p<<p<<strong<Keywords:</strong< <em<CYP450 induction, CYP3A4, drug interaction, primaquine, ritonavir</em<</p< Medicine (General) Melva Louisa verfasserin aut Arleni Arleni verfasserin aut Sri W.A. Jusman verfasserin aut Franciscus D. Suyatna verfasserin aut In Medical Journal of Indonesia Faculty of Medicine Universitas Indonesia, 2013 21(2012), 1, Seite 3-7 (DE-627)747137862 (DE-600)2716886-4 22528083 nnns volume:21 year:2012 number:1 pages:3-7 https://doi.org/10.13181/mji.v21i1.471 kostenfrei https://doaj.org/article/e03079fa98d34319a3aa17afd94d394b kostenfrei http://mji.ui.ac.id/journal/index.php/mji/article/view/471 kostenfrei https://doaj.org/toc/0853-1773 Journal toc kostenfrei https://doaj.org/toc/2252-8083 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 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_4338 GBV_ILN_4367 GBV_ILN_4700 AR 21 2012 1 3-7
allfieldsGer	10.13181/mji.v21i1.471 doi (DE-627)DOAJ050833960 (DE-599)DOAJe03079fa98d34319a3aa17afd94d394b DE-627 ger DE-627 rakwb eng R5-920 Adam Iskandarmudasyah verfasserin aut Influence of primaquine and ritonavir interaction on CYP3A4 mRNA expression in HepG2 cell culture 2012 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier <p<<strong<Background:</strong< Concomitant treatment with antimalaria and antiretroviral drug is a new challenge in the management of malaria and HIV co-infection. Primaquine is a substrate and also an inhibitor of CYP3A4, while ritonavir is a substrate, an inhibitor, and also an inducer for CYP3A4. The objective of this study is to measure the CYP3A4 mRNA expression in HepG2 cell culture induced by primaquine and ritonavir co-treatment.</p<<p<<strong<Methods:</strong< For the initial study HepG2 cells were treated with 30, 40, 50 uM of primaquine; 2, 10, 20 uM ritonavir; DMSO ≤0.1 % for negative control; or 20 uM rifampicin for positive control. While for the co-treatment study the cells were treated with 40 uM primaquine+10 uM ritonavir; DMSO ≤0.1 %; or 20 uM rifampicin for 72 hours. The cells were harvested using trypsin–EDTA and total RNA was extracted using the Tripure isolation reagent. After determining the quantity of RNA spectrophotometrically, CYP3A4 mRNA expression was quantified using real-time reverse transcription polymerase chain reaction (RT-PCR).</p<<p<<strong<Results:</strong< The expression of CYP3A4 mRNA was up-regulated (1.22 fold over control) in HepG2 cells co-treated with primaquine and ritonavir. These data suggest that the induction effect of ritonavir was more dominant than the inhibitory effect of primaquine.</p<<p<<strong<Conclusion:</strong< Concomitant administration of primaquine and ritonavir result in up-regulation of CYP3A4 mRNA expression in vitro. <em<<strong<(Med J Indones 2012;21:3-7)</strong<</em<</p<<p<<strong<Keywords:</strong< <em<CYP450 induction, CYP3A4, drug interaction, primaquine, ritonavir</em<</p< Medicine (General) Melva Louisa verfasserin aut Arleni Arleni verfasserin aut Sri W.A. Jusman verfasserin aut Franciscus D. Suyatna verfasserin aut In Medical Journal of Indonesia Faculty of Medicine Universitas Indonesia, 2013 21(2012), 1, Seite 3-7 (DE-627)747137862 (DE-600)2716886-4 22528083 nnns volume:21 year:2012 number:1 pages:3-7 https://doi.org/10.13181/mji.v21i1.471 kostenfrei https://doaj.org/article/e03079fa98d34319a3aa17afd94d394b kostenfrei http://mji.ui.ac.id/journal/index.php/mji/article/view/471 kostenfrei https://doaj.org/toc/0853-1773 Journal toc kostenfrei https://doaj.org/toc/2252-8083 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 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_4338 GBV_ILN_4367 GBV_ILN_4700 AR 21 2012 1 3-7
allfieldsSound	10.13181/mji.v21i1.471 doi (DE-627)DOAJ050833960 (DE-599)DOAJe03079fa98d34319a3aa17afd94d394b DE-627 ger DE-627 rakwb eng R5-920 Adam Iskandarmudasyah verfasserin aut Influence of primaquine and ritonavir interaction on CYP3A4 mRNA expression in HepG2 cell culture 2012 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier <p<<strong<Background:</strong< Concomitant treatment with antimalaria and antiretroviral drug is a new challenge in the management of malaria and HIV co-infection. Primaquine is a substrate and also an inhibitor of CYP3A4, while ritonavir is a substrate, an inhibitor, and also an inducer for CYP3A4. The objective of this study is to measure the CYP3A4 mRNA expression in HepG2 cell culture induced by primaquine and ritonavir co-treatment.</p<<p<<strong<Methods:</strong< For the initial study HepG2 cells were treated with 30, 40, 50 uM of primaquine; 2, 10, 20 uM ritonavir; DMSO ≤0.1 % for negative control; or 20 uM rifampicin for positive control. While for the co-treatment study the cells were treated with 40 uM primaquine+10 uM ritonavir; DMSO ≤0.1 %; or 20 uM rifampicin for 72 hours. The cells were harvested using trypsin–EDTA and total RNA was extracted using the Tripure isolation reagent. After determining the quantity of RNA spectrophotometrically, CYP3A4 mRNA expression was quantified using real-time reverse transcription polymerase chain reaction (RT-PCR).</p<<p<<strong<Results:</strong< The expression of CYP3A4 mRNA was up-regulated (1.22 fold over control) in HepG2 cells co-treated with primaquine and ritonavir. These data suggest that the induction effect of ritonavir was more dominant than the inhibitory effect of primaquine.</p<<p<<strong<Conclusion:</strong< Concomitant administration of primaquine and ritonavir result in up-regulation of CYP3A4 mRNA expression in vitro. <em<<strong<(Med J Indones 2012;21:3-7)</strong<</em<</p<<p<<strong<Keywords:</strong< <em<CYP450 induction, CYP3A4, drug interaction, primaquine, ritonavir</em<</p< Medicine (General) Melva Louisa verfasserin aut Arleni Arleni verfasserin aut Sri W.A. Jusman verfasserin aut Franciscus D. Suyatna verfasserin aut In Medical Journal of Indonesia Faculty of Medicine Universitas Indonesia, 2013 21(2012), 1, Seite 3-7 (DE-627)747137862 (DE-600)2716886-4 22528083 nnns volume:21 year:2012 number:1 pages:3-7 https://doi.org/10.13181/mji.v21i1.471 kostenfrei https://doaj.org/article/e03079fa98d34319a3aa17afd94d394b kostenfrei http://mji.ui.ac.id/journal/index.php/mji/article/view/471 kostenfrei https://doaj.org/toc/0853-1773 Journal toc kostenfrei https://doaj.org/toc/2252-8083 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 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_4338 GBV_ILN_4367 GBV_ILN_4700 AR 21 2012 1 3-7
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topic_title	R5-920 Influence of primaquine and ritonavir interaction on CYP3A4 mRNA expression in HepG2 cell culture
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title	Influence of primaquine and ritonavir interaction on CYP3A4 mRNA expression in HepG2 cell culture
ctrlnum	(DE-627)DOAJ050833960 (DE-599)DOAJe03079fa98d34319a3aa17afd94d394b
title_full	Influence of primaquine and ritonavir interaction on CYP3A4 mRNA expression in HepG2 cell culture
author_sort	Adam Iskandarmudasyah
journal	Medical Journal of Indonesia
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author_browse	Adam Iskandarmudasyah Melva Louisa Arleni Arleni Sri W.A. Jusman Franciscus D. Suyatna
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title_sort	influence of primaquine and ritonavir interaction on cyp3a4 mrna expression in hepg2 cell culture
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title_auth	Influence of primaquine and ritonavir interaction on CYP3A4 mRNA expression in HepG2 cell culture
abstract	<p<<strong<Background:</strong< Concomitant treatment with antimalaria and antiretroviral drug is a new challenge in the management of malaria and HIV co-infection. Primaquine is a substrate and also an inhibitor of CYP3A4, while ritonavir is a substrate, an inhibitor, and also an inducer for CYP3A4. The objective of this study is to measure the CYP3A4 mRNA expression in HepG2 cell culture induced by primaquine and ritonavir co-treatment.</p<<p<<strong<Methods:</strong< For the initial study HepG2 cells were treated with 30, 40, 50 uM of primaquine; 2, 10, 20 uM ritonavir; DMSO ≤0.1 % for negative control; or 20 uM rifampicin for positive control. While for the co-treatment study the cells were treated with 40 uM primaquine+10 uM ritonavir; DMSO ≤0.1 %; or 20 uM rifampicin for 72 hours. The cells were harvested using trypsin–EDTA and total RNA was extracted using the Tripure isolation reagent. After determining the quantity of RNA spectrophotometrically, CYP3A4 mRNA expression was quantified using real-time reverse transcription polymerase chain reaction (RT-PCR).</p<<p<<strong<Results:</strong< The expression of CYP3A4 mRNA was up-regulated (1.22 fold over control) in HepG2 cells co-treated with primaquine and ritonavir. These data suggest that the induction effect of ritonavir was more dominant than the inhibitory effect of primaquine.</p<<p<<strong<Conclusion:</strong< Concomitant administration of primaquine and ritonavir result in up-regulation of CYP3A4 mRNA expression in vitro. <em<<strong<(Med J Indones 2012;21:3-7)</strong<</em<</p<<p<<strong<Keywords:</strong< <em<CYP450 induction, CYP3A4, drug interaction, primaquine, ritonavir</em<</p<
abstractGer	<p<<strong<Background:</strong< Concomitant treatment with antimalaria and antiretroviral drug is a new challenge in the management of malaria and HIV co-infection. Primaquine is a substrate and also an inhibitor of CYP3A4, while ritonavir is a substrate, an inhibitor, and also an inducer for CYP3A4. The objective of this study is to measure the CYP3A4 mRNA expression in HepG2 cell culture induced by primaquine and ritonavir co-treatment.</p<<p<<strong<Methods:</strong< For the initial study HepG2 cells were treated with 30, 40, 50 uM of primaquine; 2, 10, 20 uM ritonavir; DMSO ≤0.1 % for negative control; or 20 uM rifampicin for positive control. While for the co-treatment study the cells were treated with 40 uM primaquine+10 uM ritonavir; DMSO ≤0.1 %; or 20 uM rifampicin for 72 hours. The cells were harvested using trypsin–EDTA and total RNA was extracted using the Tripure isolation reagent. After determining the quantity of RNA spectrophotometrically, CYP3A4 mRNA expression was quantified using real-time reverse transcription polymerase chain reaction (RT-PCR).</p<<p<<strong<Results:</strong< The expression of CYP3A4 mRNA was up-regulated (1.22 fold over control) in HepG2 cells co-treated with primaquine and ritonavir. These data suggest that the induction effect of ritonavir was more dominant than the inhibitory effect of primaquine.</p<<p<<strong<Conclusion:</strong< Concomitant administration of primaquine and ritonavir result in up-regulation of CYP3A4 mRNA expression in vitro. <em<<strong<(Med J Indones 2012;21:3-7)</strong<</em<</p<<p<<strong<Keywords:</strong< <em<CYP450 induction, CYP3A4, drug interaction, primaquine, ritonavir</em<</p<
abstract_unstemmed	<p<<strong<Background:</strong< Concomitant treatment with antimalaria and antiretroviral drug is a new challenge in the management of malaria and HIV co-infection. Primaquine is a substrate and also an inhibitor of CYP3A4, while ritonavir is a substrate, an inhibitor, and also an inducer for CYP3A4. The objective of this study is to measure the CYP3A4 mRNA expression in HepG2 cell culture induced by primaquine and ritonavir co-treatment.</p<<p<<strong<Methods:</strong< For the initial study HepG2 cells were treated with 30, 40, 50 uM of primaquine; 2, 10, 20 uM ritonavir; DMSO ≤0.1 % for negative control; or 20 uM rifampicin for positive control. While for the co-treatment study the cells were treated with 40 uM primaquine+10 uM ritonavir; DMSO ≤0.1 %; or 20 uM rifampicin for 72 hours. The cells were harvested using trypsin–EDTA and total RNA was extracted using the Tripure isolation reagent. After determining the quantity of RNA spectrophotometrically, CYP3A4 mRNA expression was quantified using real-time reverse transcription polymerase chain reaction (RT-PCR).</p<<p<<strong<Results:</strong< The expression of CYP3A4 mRNA was up-regulated (1.22 fold over control) in HepG2 cells co-treated with primaquine and ritonavir. These data suggest that the induction effect of ritonavir was more dominant than the inhibitory effect of primaquine.</p<<p<<strong<Conclusion:</strong< Concomitant administration of primaquine and ritonavir result in up-regulation of CYP3A4 mRNA expression in vitro. <em<<strong<(Med J Indones 2012;21:3-7)</strong<</em<</p<<p<<strong<Keywords:</strong< <em<CYP450 induction, CYP3A4, drug interaction, primaquine, ritonavir</em<</p<
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title_short	Influence of primaquine and ritonavir interaction on CYP3A4 mRNA expression in HepG2 cell culture
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After determining the quantity of RNA spectrophotometrically, CYP3A4 mRNA expression was quantified using real-time reverse transcription polymerase chain reaction (RT-PCR).</p<<p<<strong<Results:</strong< The expression of CYP3A4 mRNA was up-regulated (1.22 fold over control) in HepG2 cells co-treated with primaquine and ritonavir. These data suggest that the induction effect of ritonavir was more dominant than the inhibitory effect of primaquine.</p<<p<<strong<Conclusion:</strong< Concomitant administration of primaquine and ritonavir result in up-regulation of CYP3A4 mRNA expression in vitro. <em<<strong<(Med J Indones 2012;21:3-7)</strong<</em<</p<<p<<strong<Keywords:</strong< <em<CYP450 induction, CYP3A4, drug interaction, primaquine, ritonavir</em<</p<</subfield></datafield><datafield tag="653" ind1=" " ind2="0"><subfield code="a">Medicine (General)</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Melva Louisa</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Arleni Arleni</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Sri W.A. 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Influence of primaquine and ritonavir interaction on CYP3A4 mRNA expression in HepG2 cell culture

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