ORAL ABSORPTION AND DISPOSITION KINETICS OF LIDOCAINE HYDROCHLORIDE IN DOGS

¹ Research Laboratories, Astra Pharmaceutical Products, Inc., Worcester, Massachusetts

The blood levels of lidocaine hydrochloride in six beagles were determined after the administration of 31 mg/kg by: 1) a 1-hour constant rate i.v. infusion, 2) an exponential i.v. infusion having a half-time of 40 minutes and 3) p.o. administration in solution. A mean peak blood level of 9.2 µg/ml (range, 7.1-11.1) occurred 60 minutes after the constant rate i.v. infusion was started. The exponential i.v. infusion resulted in a mean peak blood level of 5.6 µg/ml (range, 4.7-7.5) 30 minutes after starting the infusion. After p.o. administration a mean peak blood level of 4.4 µg/ml (range, 3.1-6.8) occurred at 45 minutes. A digital computer program capable of accepting biologic models was used for kinetic analysis of the blood level data for each dog. Pertinent to the p.o. absorption of lidocaine in dogs, it was calculated that 61 to 100% (mean 78%) of the administered dose reached the general circulation, and the calculated mean absorption half-time was 38 minutes. Emesis, which occurred regularly 2.5 hours after lidocaine administration, was the only drug-related toxicologic sign noted in the dogs. In addition five beagles were given lidocaine hydrochloride (on two successive occasions) by exponential infusion through a peripheral and through the portal vein. Mean peak blood levels of 5.8 and 3.2 µg/ml were obtained after peripheral and portal vein infusion, respectively. These data support the conclusion that apparent loss of drug after p.o. administration was due to hepatic clearance.

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