Pharmacokinetic Evaluation of a Sustained-release Formulation of Trihexyphenidyl in Healthy Volunteers

Abstract

Twenty-four male subjects were randomized to receive two oral dosage forms of trihexyphenidyl HCL (α-cyclohexyl-α-phenyl-1-piperidinepropanol HCL). The dosage regimens were (1) a 5-mg immediate release (IR) tablet given twice daily at time zero and 12h later, and (2) two 5-mg sustained-release (SR) capsule formulations given daily. The number of adverse experiences following the SR formulation were ~50% of those for the IR formulation, the peak concentration (Cmax) after the SR formulation was significantly lower (p < 0.05) than that after the first dose of the IR formulation, and the time to reach Cmax(tmax) was significantly longer after the SR formulation (p < 0.05). The SR formulation maintained serum concentrations above 50, 60, and 70% of Cmax values for average time periods of 11.7, 9.4, and 5.9 h, respectively, compared with values of 1.8, 1.2, and 0.9h after the IR formulation; the differences were all significant (p < 0.05). The mean elimination half-life (t1/2) was similar (p > 0.05) after the SR (10.1 h) and IR (8.7 h) formulations. The statistical power of the study was 98.1% to detect a 20% difference in the area under the curve from time zero to time infinity (AUC0→∞) between formulations. Although the AUC0→∞ after the SR formulation was statistically smaller (p < 0.05) than after the IR tablet, the difference was <20%. Therefore, the SR formulation was bioequivalent to the IR tablet formulation of trihexyphenidyl.