Pharmacokinetics and relative bioavailability of penehyclidine hydrochloride tablet in healthy subjects / 中国药学杂志

ABSTRACT

OBJECTIVE: To explore pharmacokinetics and relative bioavailability of penehyclidine hydrochloride in healthy subjects. METHODS: This study was an open, randomized and cross-over trial design. Twelve healthy subjects were randomized to receive pharmacokinetic analysis which were performed according to the order of ABC, BCA and CAB, and then pharmacokinetic trial of multiple dose was performed following penehyclidine hydrochloride. Twenty healthy subjects were selected to receive bioavailability study following an order of BD or DB. Blood and urine samples were collected at prescribed time and then investigated by LC-MS/MS. RESULTS: The 11 of 12 cases finished the pharmacokinetic trial. The lineare ranges of penehyclidine hydrochloride in plasma and urine were 0.1-8 ng·mL-1, 1-100 ng·mL-1, respectively and accuracy of the method was within 85%-115%. The concentration-time curve of penehyclidine hydrochloride was dose dependent within the ranges of 0.4-0.8 mg after oral administration. ρmax and AUC were significantly increased (P<0.01), Vd and CL were significantly decreased (P<0.01) following multiple dose. The relative bioavailability of penehyclidine hydrochloride was (72.44±21.03)%. The average cumulative excretion rate of penehyclidine hydrochloride with original form accounted for (4.98±1.10)% of the total administered dose. CONCLUSION: The characteristic of linear pharmacokinetics of penehyclidine hydrochloride is performed in healthy subjects after oral administration. Its excretion is mostly via non-urinary system or other metabolites.