Pharmacokinetic and Bioequivalence Studies of Trospium chloride after a Single-dose Administration in Healthy Chinese Volunteers

Abstract

The study aimed to compare and evaluate the bioequivalence of a new generic preparation of trospium chloride (CAS NO:10405-02-4) capsule (20 mg, test) and the available import tablet (20 mg , reference) for the requirement of state regulatory criteria in China. A randomized- sequence, 2-period crossover study was conducted in 20 healthy Chinese male volunteers in the fasted state. Blood samples were collected before and 1, 2, 3, 4, 5, 6, 7, 8, 12, 24, 36, 48, 60 h after administration of a single oral dose of 40 mg trospium chloride capsules or tablets, followed by a 7-day washout period. The concentration of trospium chloride was determined by a LC-MS/MS method. Drug And Statistical-Version 2.0 was used to caculate the pharmacokinetics parameters and assess bioequivalence of the two preparations. It was considered bioequivalent if the 90% CIs of the mean ratios (test: reference) for C_max, AUC_0–t and AUC_0–∞ were within the range from 80% to 125%, respectively. The main pharmacokinetics parameters of test and reference were as follows: t_1/2 was (15.11±3.24) h and (16.00±3.96) h; T_max was (4.0±1.2) h and (4.1±0.9) h; C_max was (3.76±1.87) ng·mL^− 1 and (3.70±1.89) ng·mL^− 1; AUC_0–t was (33.51±14.39) ng·mL^− 1·h and (33.33±14.88) ng·mL^− 1·h, and the AUC_0–∞ was (35.20±14.88) ng·mL^− 1·h and (35.16±15.17) ng·mL^− 1·h. The ratios (test: reference) for C_max, AUC_0–t, and AUC_0–∞ were 94.0%~111.7%, 96.4%~106.8%, and 96.1%~105.3%, respectively. No significant differences in pharmacokinetic parameters were found between preparations and periods (p>0.05). No obvious adverse events were monitored throughout the study based on clinical parameters and patient reports.

Key words

trospium chloride - LC-MS/MS - pharmacokinetic - bioequivalence

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