Possible Interaction: Phenobarbital and Quinidine

“DRUG interactions with quinidine are likely to be clinically important, since quinidine is used … relatively narrow range between the therapeutic and toxic concentrations.1 An interaction between quinidine … phenobarbital has led to a reduction in the half-life of … induction by the anticonvulsants was suggested as the likely mechanism.”

“Drug-disposition studies of orally administered quinidine in four normal healthy volunteers indicated that phenobarbital and phenytoin reduced the half-life of quinidine by approximately 50 per cent (control, 3.0 to 6.1 hours, and with anticonvulsants, 1.6 to 2.6 hours).”

“After PB pretreatment plasma quinidine concentrations at the end of a 10 hr infusion increased about two-fold while the half-life decreased from a control value of about 16 hr to 6 hr.”

“Pharmacokinetic analysis of the data showed a decrease in steady-state volume of distribution (Vdss)of quinidine from an average value of 153 L to 54 L after PB treatment, while the total clearance did not change (6.6 vs. 5.6L/hr).”

“Plasma protein binding for quinidine and two of its three measured metabolites (3-hydroxy quinidine and quinidine N-oxide) were increased after PB treatment.”

“The formation rate constants calculated for two quinidine metabolites, 3-hydroxy quinidine and quinidine N-oxide, were increased after PB treatment, suggesting an induction in these two metabolic pathways.”

“The unbound nonrenal clearance of quinidine was induced by PB treatment.”

“This decrease in Vdsscould be explained by an increase in plasma protein binding of quinidine after PB treatment.”

“To study any direct interaction between PB and quinidine, PB was also added to the microsomal incubate and was found to decrease the rate constant for quinidine metabolism, suggesting inhibition of quinidine metabolism by PB.”