Pharmacokinetics of 4-aminopyridine in horses

The pharmacokinetics of 4-aminopyridine (4-AP), a drug capable of antagonizing nondepolarizing neuromuscular blocking drugs, as well as several classes of injectable sedative and anesthetic agents, were studied in 6 intact, awake horses. Plasma samples were assayed for 4-AP over a frequent sampling schedule for 8 hours after IV administration. The plasma 4-AP vs time data best fit a 2-compartment pharmacokinetic model. Distribution half-life was 7.4 minutes, elimination half-life was 259 minutes, volume of the central compartment was 0.89 L/kg, volume of distribution (area) was 1.98 L/kg, volume of distribution at steady state was 1.9 L/kg, and total clearance was 5.3 ml min(-1) kg(-1). The 259-minute elimination halflife observed in the present study is consistent with prolonged clinical effectiveness observed in a previous study of antagonism of xylazine/ketamine anesthesia by 4-AP in horses.