On the Inducibility of Cytosolic and Microsomal Carboxylesterase by Phenobarbital in Rat Tissues

Nousiainen, Unto; Hänninen, Osmo

doi:10.1111/j.1600-0773.1981.tb00873.x

Cited by 20 publications

(2 citation statements)

References 18 publications

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“…It is possible that the short length of PB pretreatment in this study may have underestimated the induction effect on hydrolysis. Results from other studies have suggested that rat liver esterase induction by PB is dependent on the dose and duration of pretreatment, and that different inducers have different magnitudes of effect on esterase induction (Lundkvist and Perlmann, 1966; Schwark and Ecobichon, 1968; Nousiainen and Hanninen, 1981). Nevertheless, current data is insufficient to ascertain an inducible effect of EIAEDs on LEV hydrolysis, but such an effect still cannot be ruled out and could explain our findings.…”

Section: Discussionmentioning

confidence: 97%

Effect of Age and Comedication on Levetiracetam Pharmacokinetics and Tolerability

et al. 2007

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Summary: Purpose:To compare pharmacokinetics and tolerability of levetiracetam (LEV) in older versus younger adults.Methods: As part of the Columbia Antiepileptic Drug Database, we retrospectively studied the pharmacokinetics and tolerability of LEV in patients who had been seen as an outpatient at our center during a 4-year period. We compared apparent clearance (CL) of LEV in the youngest (16-31 years; n = 151) and oldest (55-88 years; n = 157) quartile of 629 adult outpatients who had taken LEV. We also analyzed the frequency of adverse effects leading to dose change or discontinuation ("intolerability") and specific adverse effects in the younger versus older adults. One-year retention was determined for younger and older adults newly started on LEV at our center.Results: Mean LEV CL differed significantly between older (46.5 ml/h/kg) and younger adults (78.3 ml/h/kg). On average, older patients had a 40% lower LEV CL than younger patients. Comedication with an enzyme-inducing antiepileptic drug (EIAED; mostly carbamazepine) was associated with a 24% higher clearance of LEV compared to those who were not on EIAEDs. This difference was 37% in a subgroup of patients whose LEV CL was compared while they were on and off EIAEDs. Stepwise linear regression identified younger age and comedication with an EIAED as significant predictors of increased LEV CL. A total of 34.3% of the 629 patients (31.7% of younger vs. 40.7% of older patients; p = 0.16) reported intolerability to LEV on at least one occasion. This difference in tolerability reached significance in the group of patients newly started on LEV (26.3% vs. 41.0%; p = 0.017). Drowsiness and psychiatric/behavioral side effects were the most common adverse effects associated with LEV use in both age groups. Oneyear retention was 72% in the older group vs. 54% in the younger group (not significant).Conclusion: Older adults have lower CL than younger adults and require a mean 40% lower dose of LEV to achieve the same serum level. Comedication with an EIAED increases LEV CL by 24-37%. Younger adults tolerate LEV better than older adults, but 1-year retention was (nonsignificantly) higher in the older group.Seizures occur in an age dependent, bimodal pattern

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Section: Discussionmentioning

confidence: 97%

Effect of Age and Comedication on Levetiracetam Pharmacokinetics and Tolerability

et al. 2007

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“…xenobióticos, tais como as pertencentes ao sistema P450, as esterases de modo geral apresentam menor propensão a terem sua atividade aumentada (STROLIN BENEDETTI et al, 2003). Os autores, porém, reconhecem a importância dos trabalhos que evidenciam, in vitro, que hidrolases envolvidas no metabolismo de fármacos podem ter sua atividade aumentada, sendo inclusive o PB considerado um potente agente indutor de tais enzimas, especialmente quando administrado em altas doses e por longos períodos (KAUR;ALI, 1983;NOUSIAINEN;HÄNNINEN, 1981;HOSOKAWA, 2006;MOROI, 1977;SCHWARK;ECOBICHON, 1968;TYBRING et al, 1981). Embora conclusões acerca da real indução sofrida por esterases ainda não tenham sido estabelecidas (KAUR;ALI, 1983;PUCHE et al, 1989), a possibilidade de que elas tenham sua atividade catalítica aumentada pela administração de DAEs indutoras enzimáticas não deve ser negligenciada.…”

Section: De Acordo Comunclassified

Avaliação farmacocinética da influência de drogas antiepilépticas indutoras enzimáticas na disposição do levetiracetam em pacientes com epilepsia

Lima¹

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Hydrolysis and Oxidation of 1H‐Benzotriazole‐carboxylic Acid Esters by Rat Liver Microsomes

Jacobi

Hoffmann

1990

Archiv der Pharmazie

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On the Inducibility of Cytosolic and Microsomal Carboxylesterase by Phenobarbital in Rat Tissues

Cited by 20 publications

References 18 publications

Effect of Age and Comedication on Levetiracetam Pharmacokinetics and Tolerability

Effect of Age and Comedication on Levetiracetam Pharmacokinetics and Tolerability

Avaliação farmacocinética da influência de drogas antiepilépticas indutoras enzimáticas na disposição do levetiracetam em pacientes com epilepsia

Hydrolysis and Oxidation of 1H‐Benzotriazole‐carboxylic Acid Esters by Rat Liver Microsomes

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