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Cimetidine alters pethidine disposition in man.
British Journal of Clinical Pharmacology
|December 1, 1984
Summary
Cimetidine significantly reduces pethidine clearance and volume of distribution in healthy volunteers. This drug interaction, affecting pethidine metabolism to norpethidine, may be clinically significant, warranting caution.
Area of Science:
- Pharmacokinetics
- Drug Interactions
- Clinical Pharmacology
Background:
- Pethidine (meperidine) is an opioid analgesic.
- Cimetidine is a histamine H2 receptor antagonist known to inhibit cytochrome P450 enzymes.
- The potential for drug-drug interactions between cimetidine and pethidine requires investigation.
Purpose of the Study:
- To investigate the effect of concurrent cimetidine administration on the pharmacokinetic disposition of pethidine in healthy male volunteers.
Main Methods:
- Eight healthy male volunteers received intravenous pethidine HCl (70 mg) before and during oral cimetidine treatment (1200 mg/day).
- Pharmacokinetic parameters including total body clearance (CL) and volume of distribution at steady state (Vss) were measured.
- Concentrations of pethidine and its metabolite, norpethidine, were quantified over time.
Main Results:
- Cimetidine significantly decreased pethidine total body clearance by 22% (P < 0.05).
- Pethidine volume of distribution at steady state was reduced by 13% (P < 0.05) during cimetidine treatment.
- A 23% reduction in norpethidine area under the curve and a 29% reduction in peak norpethidine concentration were observed, suggesting reduced pethidine oxidation.
Conclusions:
- Concurrent administration of cimetidine significantly alters pethidine pharmacokinetics.
- The observed interaction, particularly the reduction in pethidine clearance and metabolism, may be clinically significant.
- Caution is advised when prescribing cimetidine and pethidine concurrently due to potential pharmacokinetic interactions.