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

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 12 h 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) 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.