Sulpiride Pharmacokinetics in Humans After Intramuscular Administration at Three Dose Levels

Abstract

Pharmacokinetics of the disinhibitory psychotropic agent sulpiride was investigated in 9 healthy male subjects after intramuscular administrations of 50, 100, and 200mg in a 3 ± 3 Latin square design. Plasma and urine concentrations were measured by HPLC for 36 and 48 h, respectively. The lowest detectable concentration was 10 ng/mL. Plasma concentration versus time and urinary excretion rate versus time curves were consistent with an open two-compartment body model, where mean ± SD apparent half-lives of the absorption from muscle, λ1 distribution, and λ2 elimination phases were 6.96 ± 2.64 min, 0.220 ± 0.120 h, and 6.74 ± 2.67 h, respectively. The initial volume of distribution was 0.145 ± 0.063 L/kg, the steady-state volume of distribution was 0.639 ± 0.184 L/kg, and the total clearance was 89.8 ± 22.3mL/min. The microscopic rate constants were k12 = 2.53 ± 1.13h−1, k21 = 0.674 ± 0.197h−1, and k10 = 0.635 ± 0.298h−1. Comparison of total clearance (89.8 mL/min), renal clearance (83.0 mL/min), and renal clearance of unbound drug (97.6 mL/min, f = 0.15) indicated that sulpiride is mainly excreted unchanged by the renal route, 93.1 ± 6.6% of the administered dose being recovered unchanged in urine. Statistical evaluation of all the above parameters, determined at the three dosage levels, did not show any variations related to dose; the pharmacokinetics of sulpiride, over the dose range tested, was therefore linear and independent of dose. The two-compartment body model proposed was validated by digital computer simulation on a small digital computer (32K).