The effect of enzyme induction on diazepam metabolism in man

Ohnhaus, E. E.; Park, B.K.; Colombo, J. P.

doi:10.1016/b978-0-08-023768-8.52465-8

Cited by 5 publications

(7 citation statements)

References 8 publications

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and 2Clinical Pharmacology, Astra Hassle AB, S-431 83 M6lndal, Sweden 1 The primary metabolism of diazepam was studied in human liver microsomes in order to investigate the kinetics and to identify the cytochrome P450 (CYP) isoforms responsible for the formation of the main diazepam metabolites, temazepam and N-desmethyldiazepam. 2 The formation kinetics of both metabolites were atypical and consistent with the occurrence of substrate activation. A sigmoid Vmax model equivalent to the Hill equation was used to fit the data.

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mentioning

confidence: 75%

Diazepam metabolism by human liver microsomes is mediated by both S‐ mephenytoin hydroxylase and CYP3A isoforms.

Andersson

Miners

Veronese

et al. 1994

Brit J Clinical Pharma

198

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…”

mentioning

confidence: 75%

Diazepam metabolism by human liver microsomes is mediated by both S‐ mephenytoin hydroxylase and CYP3A isoforms.

Andersson

Miners

Veronese

et al. 1994

Brit J Clinical Pharma

198

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“…However, in mice and guinea pigs only one metabolic pathway, either N-desmethylation or hydroxylation was influenced by phenobarbitone administration (Marucci et al, 1970). A recent study in humans has shown that the elimination of diazepam and N-desmethyldiazepam is significantly increased by induction of liver microsomial enzymes following administration of antipyrine as the inducing agent (Ohnhaus et al, 1979). However the effect of enzyme inducing antiepileptic drugs on diazepam metabolism in man has not been investigated.…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetics of diazepam in epileptic patients and normal volunteers following intravenous administration.

Dhillon¹,

Richens²

1981

Brit J Clinical Pharma

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1 The pharmacokinetics of diazepam following intravenous administration have been investigated in six normal volunteers and nine epileptic patients receiving chronic antiepileptic drug therapy. 2 After intravenous administration, serum diazepam levels declined biexponentially in all subjects. The elimination half‐life was significantly shorter and the plasma clearance significantly higher in the patients than in the normal volunteers. 3 Serum N‐desmethyldiazepam levels were higher and the time to peak serum concentration was earlier in the epileptic patients than in the controls. 4 It is suggested that the metabolism of diazepam is induced in patients treated with enzyme inducing antiepileptic drugs, although a protein binding interaction between valproic acid and diazepam may contribute to the higher plasma clearance in the epileptic patients taking sodium valproate.

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“…Marucci et al (1970) demonstrated an increase in the rate of diazepam metabolism in rats, mice and guinea pigs treated with phenobarbitone. Ohnhaus et al (1979) showed that the metabolism of diazepam in man was increased following the induction of liver microsomal enzymes by antipyrine. Dhillon & Richens (1981) found that the elimination half-life of an i.v.…”

Section: Introductionmentioning

confidence: 99%

Single dose pharmacokinetic study of clobazam in normal volunteers and epileptic patients.

Jawad¹,

Richens²,

Oxley³

1984

Brit J Clinical Pharma

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1 The pharmacokinetics of clobazam were studied in six healthy volunteers and six age and sex matched enzyme-induced epileptic patients. 2 In the epileptic patients the area under the plasma concentration-time curve for clobazam was significantly smaller and the area under the plasma concentration-time curve for N-desmethylclobazam was significantly greater than in the healthy volunteers. 3 Plasma N-desmethylclobazam concentrations were found to be much higher than those of clobazam in the epileptic patients, raising the possibility that the antiepileptic properties of clobazam are to be attributed more to its metabolite than the parent drug.

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The effect of enzyme induction on diazepam metabolism in man

Cited by 5 publications

References 8 publications

Diazepam metabolism by human liver microsomes is mediated by both S‐ mephenytoin hydroxylase and CYP3A isoforms.

Diazepam metabolism by human liver microsomes is mediated by both S‐ mephenytoin hydroxylase and CYP3A isoforms.

Pharmacokinetics of diazepam in epileptic patients and normal volunteers following intravenous administration.

Single dose pharmacokinetic study of clobazam in normal volunteers and epileptic patients.

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