Pharmacokinetics and extended-release characteristics of minocycline hydrochloride extended-release tablets in healthy volunteers / 中国药学杂志

ABSTRACT

OBJECTIVE: To investigate the pharmacokinetics of single and multiple oral doses of minocycline hydrochloride extended-release tablets and evaluate its extended-release characteristics by comparing with ordinary tablets. METHODS: Twelve healthy volunteers received a single oral dose of 45, 90 and 135 mg minocycline hydrochloride extended-release tablets respectively with a 10-day washout period. After the single-dose study, the volunteers participated in the multiple dose study in which each volunteer received 90 mg per day for 10 consecutive days. The ordinary tablets were administered by single and multiple doses as reference preparation in the end. The concentrations of minocycline in human plasma were determined by LC-MS method. RESULTS: The main pharmacokinetic parameters of a single dose of minocycline hydrochloride extended-release tablets of 45, 90 and 135 mg in 12 healthy volunteers were as follows pmax (0.4770±0.1280), (1.011±0.191) and (1.500±0.281) μg · mL-1, tmax(3.3±1.1),(3.6±0.8) and (3.4±0.7) h, t1/2 (17.1±5.4), (18.3±4.9) and (17.9±3.4) h, AUC0-t (9.391±3.019), (20.01±3.07) and (31.81±6.80) μg · h · mL-1, respectively. And those of multiple-dose of minocycline hydrochloride extended-release tablets of 90 mg were as follows pav(0.8440±0.2250) μg · mL-1, DF(1.1±0.2), pmax(1.438±0.383) μg · mL-1, tmax(3.5±0.8) h, t1/2 (19.3±4.4) h, AUC0-t(31.18±9.39) μg · h · mL-1. The main pharmacokinetic parameters of a single dose of ordinary minocycline hydrochloride tablets of 100 mg were as follows pmax(1.418±0.427) μg · mL-1, tmax (2.6±0.7) h, t1/2 (16.9±3.9) h, AUC0-t(25.35±5.80) μg · h · mL-1, and those of multiple-dose of ordinary minocycline hydrochloride tablets at 100 mg were as follows pav(1.229±0.377) μg · mL-1, DF(1.3±0.2), pmax(2.188±0.652) μg · mL-1, tmax(2.3±0.7) h, t1/2 (17.7±2.4) h, AUC0-t(44.83±16.29) μg · h · mL-1, respectively. CONCLUSION: In the range of 45-135 mg, the AUC0-t and pmax of minocycline hydrochloride extended-release tablets increased in a dose-dependent manner after single-dose administration, indicating linear pharmacokinetics. No significant gender differences were found. An accumulation of 50% in AUC0-t occurred after multiple-dose administration. The minocycline hydrochloride extended-release tablets have extended-release character comparing with ordinary tablets.