Delayed Clearance of Diazepam Due to Cimetidine

Klotz, Ulrich; Reimann, I. W.

doi:10.1056/nejm198005013021807

Cited by 320 publications

(41 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The estimated kinetic parameters of the high and low affinity components are listed in Table 1 showing that control values are similar to those previously reported for human liver microsomes (Boobis et al, 1981;Woodhouse et al, 1984). (Gugler & Jensen, 1984;Klotz & Reimann, 1980). Omeprazole (40 mg day-l) increased the half-life and decreased the total plasma clearance of diazepam by 130% and 54%, respectively (Gugler & Jensen, 1984).…”

Section: Resultssupporting

confidence: 78%

“…Omeprazole (40 mg day-l) increased the half-life and decreased the total plasma clearance of diazepam by 130% and 54%, respectively (Gugler & Jensen, 1984). This inhibition compares to that of cimetidine which has been reported to increase the half-life of diazepam by 53% and decrease its plasma clearance by 43% (Klotz & Reimann, 1980). Although the daily doses of omeprazole and cimetidine are 20-40 mg and 800-1000 mg, respectively, peak plasma concentrations of 0.9 ,ug ml-' of omeprazole are observed in man following a single oral dose of 40 mg whereas after a single 400 mg dose of cimetidine 2.5 ,ug ml-[ are detected (Somogyi & Gugler, 1983 …”

Section: Resultsmentioning

confidence: 86%

See 1 more Smart Citation

Inhibition of human liver cytochrome P‐450 by omeprazole.

Jensen¹,

Gugler²

1986

Brit J Clinical Pharma

View full text Add to dashboard Cite

The effects of omeprazole on cytochrome P‐450 mediated 7‐ethoxycoumarin deethylation were studied in human liver microsomes. Omeprazole inhibited both the high and low affinity components of deethylation, with an estimated Ki of 0.03 mM for the high affinity component. The results are further evidence that the previously reported prolongation of the half‐life of diazepam by omeprazole in vivo is due to inhibition of cytochrome P‐450 monooxygenases.

show abstract

Section: Resultssupporting

confidence: 78%

Section: Resultsmentioning

confidence: 86%

Inhibition of human liver cytochrome P‐450 by omeprazole.

Jensen¹,

Gugler²

1986

Brit J Clinical Pharma

View full text Add to dashboard Cite

show abstract

“…It is well known that cimetidine inhibits cytochrome P450 [I] and thus slows the metabolism of diazepam [2] and midazolam [3]. Ranitidine also inhibits P450, but to much less an extent than cimetidine [4] and studies of its effect on the metabolism of these benzodiazepines have provided contradictory results [5-71.…”

Section: Introductionmentioning

confidence: 99%

“…Patients with these symptoms are routinely referred for day-case endoscopy for which benzodiazepines are used as sedation. It is essential to establish which factors will affect the rate of recovery after sedation in order to predict the extent of residual functional impairment in patients released into the community.It is well known that cimetidine inhibits cytochrome P450 [I] and thus slows the metabolism of diazepam [2] and midazolam [3]. Ranitidine also inhibits P450, but to much less an extent than cimetidine [4] and studies of its effect on the metabolism of these benzodiazepines have provided contradictory results [5-71.…”

mentioning

confidence: 99%

Interaction of H₂‐receptor antagonists and benzodiazepine sedation

et al. 1993

View full text Add to dashboard Cite

SummaryH,-receptor antagonists differentially inhibit cytochrome P450 and this may affect the rate at which benzodiazepines are metabolised. However, it is not known whether this delayed clearance results in prolonged psychomotor impairment. In a randomised double-blind trial 28 healthy volunteers received two single doses of midazolam (0.07 mg.kg-') at an interval of one week during which they took cimetidine 400 mg, ranitidine 150 mg or placebo, each twice daily. Recovery from the benzodiazepine was monitored on each occasion over a 12 h period using a battery of psychometric tests. There was wide individual variation in performance; however, an overall measure of impairment indicated a significant difference at 2.5 h ( p < 0.05), the cimetidine group having a high impairment score. This decrement appeared to be in cognitive and psychomotor functions and was not rejected in the subjective assessment. Key wordsHistamine; cimetidine, ranitidine. Recovery; psychometric tests. Hypnotics, benzodiazepines; midazolam.Cimetidine and ranitidine aid peptic ulcer healing by reducing the gastric acid output as a result of their H,-receptor blocking action. They may also relieve heartburn in peptic oesophagitis, in high doses reduce gastric acid output in the Zollinger-Ellison syndrome, and inhibit acid breakdown of pancreatic enzyme supplements. Patients with these symptoms are routinely referred for day-case endoscopy for which benzodiazepines are used as sedation. It is essential to establish which factors will affect the rate of recovery after sedation in order to predict the extent of residual functional impairment in patients released into the community.It is well known that cimetidine inhibits cytochrome P450 [I] and thus slows the metabolism of diazepam [2] and midazolam [3]. Ranitidine also inhibits P450, but to much less an extent than cimetidine [4] and studies of its effect on the metabolism of these benzodiazepines have provided contradictory results [5-71.Theoretically, those patients taking cimetidine will metabolise benzodiazepines more. slowly than those receiving ranitidine. If the rate of metabolism of the sedatives may be differentially affected by those two H,-receptor blockers, then it is necessary to determine whether the rate of psychomotor recovery is also differentially affected. It has not been established whether this reduced hepatic metabolism of the benzodiazepines results in prolonged psychomotor impairment. Studies which have used psychometric tests have not provided conclusive evidence. Dundee and colleagues [5] found no significant effect of ranitidine on a single dose of midazolam on observer assessment of sedation. Although Gough and colleagues [S] found a significant difference in the plasma concentrations and of the elimination half-life of diazepam after cimetidine compared to placebo, they found no significant difference in cognitive impairment using the Digit Symbol Substitution Test (DSST) and visual analogue scales (VAS). Similarly Greenblatt and colleagues [9] administered cimeti...

show abstract

“…Other drugs the pharmacokinetics of which have been found to be affected by cimetidine, although the result might be less hazardous, include diazepam and antipyrine (Klotz & Reiman, 1980), chlordiazepoxide (Desmond et al, 1980) and propranolol (Feely et al, 1981;Heagerty etal., 1981).…”

Section: Introductionmentioning

confidence: 99%

The effect of pretreatment with cimetidine on the bioavailability and disposition of atenolol and metoprolol.

Jj¹,

Streurman²,

Regårdh³

1982

Brit J Clinical Pharma

View full text Add to dashboard Cite

1 Plasma levels of atenolol and metoprolol and their effects on exercise heart rate have been studied after oral administration of single doses of 100 mg of the two drugs in ordinary tablets alone and during concomittant cimetidine medication of 1 g per day.2 Cimetidine caused no significant changes in the bioavailability of any of the two p-adrenoceptor blockers and the rate of elimination of metoprolol was unaffected by the histamine H2-receptor blocker. A slight but significant increase in the elimination half-life from 6.5 + 0.6 to 7.9 0.6 (P < 0.05) was noted for atenolol after pretreatment with cimetidine. The f3-adrenoceptor blocking effect was about the same for the used doses of atenolol and metoprolol and it was not changed during cimetidine therapy.

show abstract

Delayed Clearance of Diazepam Due to Cimetidine

Cited by 320 publications

References 9 publications

Inhibition of human liver cytochrome P‐450 by omeprazole.

Inhibition of human liver cytochrome P‐450 by omeprazole.

Interaction of H₂‐receptor antagonists and benzodiazepine sedation

The effect of pretreatment with cimetidine on the bioavailability and disposition of atenolol and metoprolol.

Contact Info

Product

Resources

About

Delayed Clearance of Diazepam Due to Cimetidine

Cited by 320 publications

References 9 publications

Inhibition of human liver cytochrome P‐450 by omeprazole.

Inhibition of human liver cytochrome P‐450 by omeprazole.

Interaction of H2‐receptor antagonists and benzodiazepine sedation

The effect of pretreatment with cimetidine on the bioavailability and disposition of atenolol and metoprolol.

Contact Info

Product

Resources

About

Interaction of H₂‐receptor antagonists and benzodiazepine sedation