Effect of duration of lidocaine infusion and route of cimetidine administration on lidocaine pharmacokinetics.
The effects of the duration of lidocaine infusion and the route of cimetidine administration on lidocaine pharmacokinetics were evaluated in a randomized, three-phase crossover study of six healthy men. Lidocaine hydrochloride 100 mg was administered intravenously over two minutes, and plasma lidocaine concentrations were determined before treatment and at various intervals for three hours. Immediately after the three-hour sample was obtained, a second 100-mg dose of lidocaine hydrochloride was given, followed by a 21-hour constant infusion at a rate of 2 mg/min. Plasma lidocaine concentrations were determined at various intervals during the infusion and for eight hours afterward. Urine was collected during the last five hours of the infusion and assayed for lidocaine, monoethylglycinexylidide (MEGX), and glycinexylidide (GX). The following treatments were administered to each subject in a crossover manner: a placebo tablet every six hours, beginning two days before lidocaine administration; cimetidine 300 mg orally every six hours, beginning two days before lidocaine administration; and cimetidine hydrochloride 300 mg i.v. every six hours, beginning one hour before lidocaine administration. Each medication was given until the lidocaine infusion was discontinued. Subjects fasted and remained supine throughout each treatment period. Oral cimetidine increased the area under the concentration-time curve for lidocaine by 14.7% and increased the elimination half-life of lidocaine; i.v. cimetidine did not have a significant effect on lidocaine disposition. Lidocaine clearance was 34% lower under steady-state than single-dose conditions, but the effects of cimetidine on lidocaine disposition were similar under both conditions.(ABSTRACT TRUNCATED AT 250 WORDS)
D000328:Adult; D002927:Cimetidine / Q000008:administration & dosage / Q000009:adverse effects*; D003640:Dealkylation; D004347:Drug Interactions; D006801:Humans; D007262:Infusions, Intravenous; D007700:Kinetics; D008012:Lidocaine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000378:metabolism* / Q000652:urine; D008297:Male
D002927:Cimetidine; D008012:Lidocaine; C001306:glycinexylidide; C001173:monoethylglycinexylidide