Population pharmacodynamic modelling of lorazepam- and midazolam-induced sedation upon long-term continuous infusion in critically ill patients
Objective The objective of the present investigation was to develop a population pharmacodynamic model for midazolam- and lorazepam-induced sedation upon long-term continuous infusion in critically ill patients. Methods The study was conducted in 59 patients receiving lorazepam and 54 patients recei...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Swart, Eleonora L. [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2006 |
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| Schlagwörter: |
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| Anmerkung: |
© Springer-Verlag 2006 |
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| Übergeordnetes Werk: |
Enthalten in: European journal of clinical pharmacology - Berlin : Springer, 1968, 62(2006), 3 vom: 20. Jan., Seite 185-194 |
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| Übergeordnetes Werk: |
volume:62 ; year:2006 ; number:3 ; day:20 ; month:01 ; pages:185-194 |
| Links: |
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| DOI / URN: |
10.1007/s00228-005-0085-8 |
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| 100 | 1 | |a Swart, Eleonora L. |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Population pharmacodynamic modelling of lorazepam- and midazolam-induced sedation upon long-term continuous infusion in critically ill patients |
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| 520 | |a Objective The objective of the present investigation was to develop a population pharmacodynamic model for midazolam- and lorazepam-induced sedation upon long-term continuous infusion in critically ill patients. Methods The study was conducted in 59 patients receiving lorazepam and 54 patients receiving midazolam by continuous infusion for at least 24 h. Repeated blood samples were obtained for determination of the concentrations of lorazepam and midazolam. The level of sedation was assessed using a 5-point sedation scale. Results The pharmacokinetics of lorazepam and midazolam was described with previously proposed pharmacokinetic models. For the pharmacodynamics, the probability that the sedation was equal to or more than a specific score was described using a sigmoid $ E_{max} $ model. The $ EC_{50} $ values of lorazepam for the sedation scores equal or larger than 2–5 were 6.1, 57, 184 and 529 ng/ml, respectively. The corresponding values for midazolam were 216, 483, 1100 and 2200 ng/ml. Inter-individual variability in the $ EC_{50} $ values was relatively high with a CV of 68% for lorazepam and 86% for midazolam (p=0.035). No covariates explaining part of the observed inter-individual variability were identified. Conclusion The population pharmacodynamic model shows a similarly wide intra- and inter-individual variability in the pharmacodynamics of both lorazepam and midazolam. Thus, the previously observed differences in “ease of titration” between lorazepam and midazolam are unrelated to pharmacodynamic factors. | ||
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| 650 | 4 | |a Midazolam |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Pharmacodynamics |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Intensive care unit |7 (dpeaa)DE-He213 | |
| 700 | 1 | |a Zuideveld, Klaas P. |4 aut | |
| 700 | 1 | |a de Jongh, Joost |4 aut | |
| 700 | 1 | |a Danhof, Meindert |4 aut | |
| 700 | 1 | |a Thijs, Lambertus G. |4 aut | |
| 700 | 1 | |a Strack van Schijndel, Robert M. J. |4 aut | |
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10.1007/s00228-005-0085-8 doi (DE-627)SPR002568977 (SPR)s00228-005-0085-8-e DE-627 ger DE-627 rakwb eng Swart, Eleonora L. verfasserin aut Population pharmacodynamic modelling of lorazepam- and midazolam-induced sedation upon long-term continuous infusion in critically ill patients 2006 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Springer-Verlag 2006 Objective The objective of the present investigation was to develop a population pharmacodynamic model for midazolam- and lorazepam-induced sedation upon long-term continuous infusion in critically ill patients. Methods The study was conducted in 59 patients receiving lorazepam and 54 patients receiving midazolam by continuous infusion for at least 24 h. Repeated blood samples were obtained for determination of the concentrations of lorazepam and midazolam. The level of sedation was assessed using a 5-point sedation scale. Results The pharmacokinetics of lorazepam and midazolam was described with previously proposed pharmacokinetic models. For the pharmacodynamics, the probability that the sedation was equal to or more than a specific score was described using a sigmoid $ E_{max} $ model. The $ EC_{50} $ values of lorazepam for the sedation scores equal or larger than 2–5 were 6.1, 57, 184 and 529 ng/ml, respectively. The corresponding values for midazolam were 216, 483, 1100 and 2200 ng/ml. Inter-individual variability in the $ EC_{50} $ values was relatively high with a CV of 68% for lorazepam and 86% for midazolam (p=0.035). No covariates explaining part of the observed inter-individual variability were identified. Conclusion The population pharmacodynamic model shows a similarly wide intra- and inter-individual variability in the pharmacodynamics of both lorazepam and midazolam. Thus, the previously observed differences in “ease of titration” between lorazepam and midazolam are unrelated to pharmacodynamic factors. Lorazepam (dpeaa)DE-He213 Midazolam (dpeaa)DE-He213 Pharmacodynamics (dpeaa)DE-He213 Intensive care unit (dpeaa)DE-He213 Zuideveld, Klaas P. aut de Jongh, Joost aut Danhof, Meindert aut Thijs, Lambertus G. aut Strack van Schijndel, Robert M. J. aut Enthalten in European journal of clinical pharmacology Berlin : Springer, 1968 62(2006), 3 vom: 20. Jan., Seite 185-194 (DE-627)253722829 (DE-600)1459058-X 1432-1041 nnns volume:62 year:2006 number:3 day:20 month:01 pages:185-194 https://dx.doi.org/10.1007/s00228-005-0085-8 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 62 2006 3 20 01 185-194 |
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10.1007/s00228-005-0085-8 doi (DE-627)SPR002568977 (SPR)s00228-005-0085-8-e DE-627 ger DE-627 rakwb eng Swart, Eleonora L. verfasserin aut Population pharmacodynamic modelling of lorazepam- and midazolam-induced sedation upon long-term continuous infusion in critically ill patients 2006 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Springer-Verlag 2006 Objective The objective of the present investigation was to develop a population pharmacodynamic model for midazolam- and lorazepam-induced sedation upon long-term continuous infusion in critically ill patients. Methods The study was conducted in 59 patients receiving lorazepam and 54 patients receiving midazolam by continuous infusion for at least 24 h. Repeated blood samples were obtained for determination of the concentrations of lorazepam and midazolam. The level of sedation was assessed using a 5-point sedation scale. Results The pharmacokinetics of lorazepam and midazolam was described with previously proposed pharmacokinetic models. For the pharmacodynamics, the probability that the sedation was equal to or more than a specific score was described using a sigmoid $ E_{max} $ model. The $ EC_{50} $ values of lorazepam for the sedation scores equal or larger than 2–5 were 6.1, 57, 184 and 529 ng/ml, respectively. The corresponding values for midazolam were 216, 483, 1100 and 2200 ng/ml. Inter-individual variability in the $ EC_{50} $ values was relatively high with a CV of 68% for lorazepam and 86% for midazolam (p=0.035). No covariates explaining part of the observed inter-individual variability were identified. Conclusion The population pharmacodynamic model shows a similarly wide intra- and inter-individual variability in the pharmacodynamics of both lorazepam and midazolam. Thus, the previously observed differences in “ease of titration” between lorazepam and midazolam are unrelated to pharmacodynamic factors. Lorazepam (dpeaa)DE-He213 Midazolam (dpeaa)DE-He213 Pharmacodynamics (dpeaa)DE-He213 Intensive care unit (dpeaa)DE-He213 Zuideveld, Klaas P. aut de Jongh, Joost aut Danhof, Meindert aut Thijs, Lambertus G. aut Strack van Schijndel, Robert M. J. aut Enthalten in European journal of clinical pharmacology Berlin : Springer, 1968 62(2006), 3 vom: 20. Jan., Seite 185-194 (DE-627)253722829 (DE-600)1459058-X 1432-1041 nnns volume:62 year:2006 number:3 day:20 month:01 pages:185-194 https://dx.doi.org/10.1007/s00228-005-0085-8 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 62 2006 3 20 01 185-194 |
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10.1007/s00228-005-0085-8 doi (DE-627)SPR002568977 (SPR)s00228-005-0085-8-e DE-627 ger DE-627 rakwb eng Swart, Eleonora L. verfasserin aut Population pharmacodynamic modelling of lorazepam- and midazolam-induced sedation upon long-term continuous infusion in critically ill patients 2006 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Springer-Verlag 2006 Objective The objective of the present investigation was to develop a population pharmacodynamic model for midazolam- and lorazepam-induced sedation upon long-term continuous infusion in critically ill patients. Methods The study was conducted in 59 patients receiving lorazepam and 54 patients receiving midazolam by continuous infusion for at least 24 h. Repeated blood samples were obtained for determination of the concentrations of lorazepam and midazolam. The level of sedation was assessed using a 5-point sedation scale. Results The pharmacokinetics of lorazepam and midazolam was described with previously proposed pharmacokinetic models. For the pharmacodynamics, the probability that the sedation was equal to or more than a specific score was described using a sigmoid $ E_{max} $ model. The $ EC_{50} $ values of lorazepam for the sedation scores equal or larger than 2–5 were 6.1, 57, 184 and 529 ng/ml, respectively. The corresponding values for midazolam were 216, 483, 1100 and 2200 ng/ml. Inter-individual variability in the $ EC_{50} $ values was relatively high with a CV of 68% for lorazepam and 86% for midazolam (p=0.035). No covariates explaining part of the observed inter-individual variability were identified. Conclusion The population pharmacodynamic model shows a similarly wide intra- and inter-individual variability in the pharmacodynamics of both lorazepam and midazolam. Thus, the previously observed differences in “ease of titration” between lorazepam and midazolam are unrelated to pharmacodynamic factors. Lorazepam (dpeaa)DE-He213 Midazolam (dpeaa)DE-He213 Pharmacodynamics (dpeaa)DE-He213 Intensive care unit (dpeaa)DE-He213 Zuideveld, Klaas P. aut de Jongh, Joost aut Danhof, Meindert aut Thijs, Lambertus G. aut Strack van Schijndel, Robert M. J. aut Enthalten in European journal of clinical pharmacology Berlin : Springer, 1968 62(2006), 3 vom: 20. Jan., Seite 185-194 (DE-627)253722829 (DE-600)1459058-X 1432-1041 nnns volume:62 year:2006 number:3 day:20 month:01 pages:185-194 https://dx.doi.org/10.1007/s00228-005-0085-8 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 62 2006 3 20 01 185-194 |
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10.1007/s00228-005-0085-8 doi (DE-627)SPR002568977 (SPR)s00228-005-0085-8-e DE-627 ger DE-627 rakwb eng Swart, Eleonora L. verfasserin aut Population pharmacodynamic modelling of lorazepam- and midazolam-induced sedation upon long-term continuous infusion in critically ill patients 2006 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Springer-Verlag 2006 Objective The objective of the present investigation was to develop a population pharmacodynamic model for midazolam- and lorazepam-induced sedation upon long-term continuous infusion in critically ill patients. Methods The study was conducted in 59 patients receiving lorazepam and 54 patients receiving midazolam by continuous infusion for at least 24 h. Repeated blood samples were obtained for determination of the concentrations of lorazepam and midazolam. The level of sedation was assessed using a 5-point sedation scale. Results The pharmacokinetics of lorazepam and midazolam was described with previously proposed pharmacokinetic models. For the pharmacodynamics, the probability that the sedation was equal to or more than a specific score was described using a sigmoid $ E_{max} $ model. The $ EC_{50} $ values of lorazepam for the sedation scores equal or larger than 2–5 were 6.1, 57, 184 and 529 ng/ml, respectively. The corresponding values for midazolam were 216, 483, 1100 and 2200 ng/ml. Inter-individual variability in the $ EC_{50} $ values was relatively high with a CV of 68% for lorazepam and 86% for midazolam (p=0.035). No covariates explaining part of the observed inter-individual variability were identified. Conclusion The population pharmacodynamic model shows a similarly wide intra- and inter-individual variability in the pharmacodynamics of both lorazepam and midazolam. Thus, the previously observed differences in “ease of titration” between lorazepam and midazolam are unrelated to pharmacodynamic factors. Lorazepam (dpeaa)DE-He213 Midazolam (dpeaa)DE-He213 Pharmacodynamics (dpeaa)DE-He213 Intensive care unit (dpeaa)DE-He213 Zuideveld, Klaas P. aut de Jongh, Joost aut Danhof, Meindert aut Thijs, Lambertus G. aut Strack van Schijndel, Robert M. J. aut Enthalten in European journal of clinical pharmacology Berlin : Springer, 1968 62(2006), 3 vom: 20. Jan., Seite 185-194 (DE-627)253722829 (DE-600)1459058-X 1432-1041 nnns volume:62 year:2006 number:3 day:20 month:01 pages:185-194 https://dx.doi.org/10.1007/s00228-005-0085-8 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 62 2006 3 20 01 185-194 |
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10.1007/s00228-005-0085-8 doi (DE-627)SPR002568977 (SPR)s00228-005-0085-8-e DE-627 ger DE-627 rakwb eng Swart, Eleonora L. verfasserin aut Population pharmacodynamic modelling of lorazepam- and midazolam-induced sedation upon long-term continuous infusion in critically ill patients 2006 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Springer-Verlag 2006 Objective The objective of the present investigation was to develop a population pharmacodynamic model for midazolam- and lorazepam-induced sedation upon long-term continuous infusion in critically ill patients. Methods The study was conducted in 59 patients receiving lorazepam and 54 patients receiving midazolam by continuous infusion for at least 24 h. Repeated blood samples were obtained for determination of the concentrations of lorazepam and midazolam. The level of sedation was assessed using a 5-point sedation scale. Results The pharmacokinetics of lorazepam and midazolam was described with previously proposed pharmacokinetic models. For the pharmacodynamics, the probability that the sedation was equal to or more than a specific score was described using a sigmoid $ E_{max} $ model. The $ EC_{50} $ values of lorazepam for the sedation scores equal or larger than 2–5 were 6.1, 57, 184 and 529 ng/ml, respectively. The corresponding values for midazolam were 216, 483, 1100 and 2200 ng/ml. Inter-individual variability in the $ EC_{50} $ values was relatively high with a CV of 68% for lorazepam and 86% for midazolam (p=0.035). No covariates explaining part of the observed inter-individual variability were identified. Conclusion The population pharmacodynamic model shows a similarly wide intra- and inter-individual variability in the pharmacodynamics of both lorazepam and midazolam. Thus, the previously observed differences in “ease of titration” between lorazepam and midazolam are unrelated to pharmacodynamic factors. Lorazepam (dpeaa)DE-He213 Midazolam (dpeaa)DE-He213 Pharmacodynamics (dpeaa)DE-He213 Intensive care unit (dpeaa)DE-He213 Zuideveld, Klaas P. aut de Jongh, Joost aut Danhof, Meindert aut Thijs, Lambertus G. aut Strack van Schijndel, Robert M. J. aut Enthalten in European journal of clinical pharmacology Berlin : Springer, 1968 62(2006), 3 vom: 20. Jan., Seite 185-194 (DE-627)253722829 (DE-600)1459058-X 1432-1041 nnns volume:62 year:2006 number:3 day:20 month:01 pages:185-194 https://dx.doi.org/10.1007/s00228-005-0085-8 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 62 2006 3 20 01 185-194 |
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Enthalten in European journal of clinical pharmacology 62(2006), 3 vom: 20. Jan., Seite 185-194 volume:62 year:2006 number:3 day:20 month:01 pages:185-194 |
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Lorazepam Midazolam Pharmacodynamics Intensive care unit |
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Swart, Eleonora L. @@aut@@ Zuideveld, Klaas P. @@aut@@ de Jongh, Joost @@aut@@ Danhof, Meindert @@aut@@ Thijs, Lambertus G. @@aut@@ Strack van Schijndel, Robert M. J. @@aut@@ |
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Methods The study was conducted in 59 patients receiving lorazepam and 54 patients receiving midazolam by continuous infusion for at least 24 h. Repeated blood samples were obtained for determination of the concentrations of lorazepam and midazolam. The level of sedation was assessed using a 5-point sedation scale. Results The pharmacokinetics of lorazepam and midazolam was described with previously proposed pharmacokinetic models. For the pharmacodynamics, the probability that the sedation was equal to or more than a specific score was described using a sigmoid $ E_{max} $ model. The $ EC_{50} $ values of lorazepam for the sedation scores equal or larger than 2–5 were 6.1, 57, 184 and 529 ng/ml, respectively. The corresponding values for midazolam were 216, 483, 1100 and 2200 ng/ml. Inter-individual variability in the $ EC_{50} $ values was relatively high with a CV of 68% for lorazepam and 86% for midazolam (p=0.035). No covariates explaining part of the observed inter-individual variability were identified. Conclusion The population pharmacodynamic model shows a similarly wide intra- and inter-individual variability in the pharmacodynamics of both lorazepam and midazolam. 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Swart, Eleonora L. |
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Swart, Eleonora L. misc Lorazepam misc Midazolam misc Pharmacodynamics misc Intensive care unit Population pharmacodynamic modelling of lorazepam- and midazolam-induced sedation upon long-term continuous infusion in critically ill patients |
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Population pharmacodynamic modelling of lorazepam- and midazolam-induced sedation upon long-term continuous infusion in critically ill patients Lorazepam (dpeaa)DE-He213 Midazolam (dpeaa)DE-He213 Pharmacodynamics (dpeaa)DE-He213 Intensive care unit (dpeaa)DE-He213 |
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Population pharmacodynamic modelling of lorazepam- and midazolam-induced sedation upon long-term continuous infusion in critically ill patients |
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Population pharmacodynamic modelling of lorazepam- and midazolam-induced sedation upon long-term continuous infusion in critically ill patients |
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Swart, Eleonora L. |
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Swart, Eleonora L. Zuideveld, Klaas P. de Jongh, Joost Danhof, Meindert Thijs, Lambertus G. Strack van Schijndel, Robert M. J. |
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Swart, Eleonora L. |
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10.1007/s00228-005-0085-8 |
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population pharmacodynamic modelling of lorazepam- and midazolam-induced sedation upon long-term continuous infusion in critically ill patients |
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Population pharmacodynamic modelling of lorazepam- and midazolam-induced sedation upon long-term continuous infusion in critically ill patients |
| abstract |
Objective The objective of the present investigation was to develop a population pharmacodynamic model for midazolam- and lorazepam-induced sedation upon long-term continuous infusion in critically ill patients. Methods The study was conducted in 59 patients receiving lorazepam and 54 patients receiving midazolam by continuous infusion for at least 24 h. Repeated blood samples were obtained for determination of the concentrations of lorazepam and midazolam. The level of sedation was assessed using a 5-point sedation scale. Results The pharmacokinetics of lorazepam and midazolam was described with previously proposed pharmacokinetic models. For the pharmacodynamics, the probability that the sedation was equal to or more than a specific score was described using a sigmoid $ E_{max} $ model. The $ EC_{50} $ values of lorazepam for the sedation scores equal or larger than 2–5 were 6.1, 57, 184 and 529 ng/ml, respectively. The corresponding values for midazolam were 216, 483, 1100 and 2200 ng/ml. Inter-individual variability in the $ EC_{50} $ values was relatively high with a CV of 68% for lorazepam and 86% for midazolam (p=0.035). No covariates explaining part of the observed inter-individual variability were identified. Conclusion The population pharmacodynamic model shows a similarly wide intra- and inter-individual variability in the pharmacodynamics of both lorazepam and midazolam. Thus, the previously observed differences in “ease of titration” between lorazepam and midazolam are unrelated to pharmacodynamic factors. © Springer-Verlag 2006 |
| abstractGer |
Objective The objective of the present investigation was to develop a population pharmacodynamic model for midazolam- and lorazepam-induced sedation upon long-term continuous infusion in critically ill patients. Methods The study was conducted in 59 patients receiving lorazepam and 54 patients receiving midazolam by continuous infusion for at least 24 h. Repeated blood samples were obtained for determination of the concentrations of lorazepam and midazolam. The level of sedation was assessed using a 5-point sedation scale. Results The pharmacokinetics of lorazepam and midazolam was described with previously proposed pharmacokinetic models. For the pharmacodynamics, the probability that the sedation was equal to or more than a specific score was described using a sigmoid $ E_{max} $ model. The $ EC_{50} $ values of lorazepam for the sedation scores equal or larger than 2–5 were 6.1, 57, 184 and 529 ng/ml, respectively. The corresponding values for midazolam were 216, 483, 1100 and 2200 ng/ml. Inter-individual variability in the $ EC_{50} $ values was relatively high with a CV of 68% for lorazepam and 86% for midazolam (p=0.035). No covariates explaining part of the observed inter-individual variability were identified. Conclusion The population pharmacodynamic model shows a similarly wide intra- and inter-individual variability in the pharmacodynamics of both lorazepam and midazolam. Thus, the previously observed differences in “ease of titration” between lorazepam and midazolam are unrelated to pharmacodynamic factors. © Springer-Verlag 2006 |
| abstract_unstemmed |
Objective The objective of the present investigation was to develop a population pharmacodynamic model for midazolam- and lorazepam-induced sedation upon long-term continuous infusion in critically ill patients. Methods The study was conducted in 59 patients receiving lorazepam and 54 patients receiving midazolam by continuous infusion for at least 24 h. Repeated blood samples were obtained for determination of the concentrations of lorazepam and midazolam. The level of sedation was assessed using a 5-point sedation scale. Results The pharmacokinetics of lorazepam and midazolam was described with previously proposed pharmacokinetic models. For the pharmacodynamics, the probability that the sedation was equal to or more than a specific score was described using a sigmoid $ E_{max} $ model. The $ EC_{50} $ values of lorazepam for the sedation scores equal or larger than 2–5 were 6.1, 57, 184 and 529 ng/ml, respectively. The corresponding values for midazolam were 216, 483, 1100 and 2200 ng/ml. Inter-individual variability in the $ EC_{50} $ values was relatively high with a CV of 68% for lorazepam and 86% for midazolam (p=0.035). No covariates explaining part of the observed inter-individual variability were identified. Conclusion The population pharmacodynamic model shows a similarly wide intra- and inter-individual variability in the pharmacodynamics of both lorazepam and midazolam. Thus, the previously observed differences in “ease of titration” between lorazepam and midazolam are unrelated to pharmacodynamic factors. © Springer-Verlag 2006 |
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Population pharmacodynamic modelling of lorazepam- and midazolam-induced sedation upon long-term continuous infusion in critically ill patients |
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Zuideveld, Klaas P. de Jongh, Joost Danhof, Meindert Thijs, Lambertus G. Strack van Schijndel, Robert M. J. |
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Zuideveld, Klaas P. de Jongh, Joost Danhof, Meindert Thijs, Lambertus G. Strack van Schijndel, Robert M. J. |
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| score |
7.401534 |