Preclinical and clinical pharmacokinetics of pirmenol

Metabolic disposition and pharmacokinetics of pirmenol were studied in laboratory animals and in patients with premature ventricular beats. After intravenous administration, pirmenol pharmacokinetics were adequately characterized by a 2-compartment body model with elimination half-lives of 3 to 4 hours in animals and 6 to 9 hours in patients. Oral absorption of pirmenol was complete and devoid of significant first-pass metabolism. Systemic oral bioavailability averaged 87% in humans. Pirmenol was 83% to 90% bound to human plasma proteins. Animal studies showed that pirmenol was widely distributed in tissues resulting in higher drug concentrations in tissue than in plasma. Pirmenol was partly eliminated as unchanged drug and partly metabolized. Tracer studies in animals showed that approximately 40% to 50% of the administered radioactive dose was excreted in the urine and the remainder in the feces. The latter route was due to excretion of radioactivity in the bile. Evidence of enterohepatic recycling was established in bile duct-cannulated monkeys. Approximately 23% to 31% of the administered pirmenol dose was recovered unchanged in human urine.