AIM: To investigate the pharmacokinetics and safety of gemifloxacin in healthy Chinese subjects and provide some theoretic bases for its reasonable application in clinic. METHODS:(1) 12 healthy Chinese male subjects were enrolled in this study with an open label, 3-period cross-over oral single dosing pharmacokinetic study. The subjects sequentially took 3 doses of gemifloxacin (160, 320 and 480 mg) according to the randomization schedule. (2)20 subjects were chosen to participate in a randomized, double blind, multiple dosing pharmacokinetic study. The subjects were orally given 320 mg gemifloxacin or matching placebo once daily for 7 consecutive days. Clinical observation and laboratory test were performed during the study for the assessment of adverse events. The concentrations of gemifloxacin in serum and urine were determined by high performance liquid chromatogram (HPLC). The pharmacokinetic parameters were analysed by 3P97 analysis software. RESULTS: (1)The pharmacokinetic courses following single crossover oral dose of 160, 320 and 480 mg were all in accordance with the two-compartment model. The Cmax were (0.70±0.19), (1.40±0.32) and (1.84±0.35) mg/L, respectively. The mean times to reach Cmax were (1.2±0.4), (1.1±0.4) and (1.4±0.4) h, respectively. The values of t1/2β were (7.0±1.0), (6.7±0.8) and (6.9±0.8) h, respectively. The AUC0-∞ were (4.1±0.6), (7.5±1.1) and (11.7±1.7) mg·L-1·h, respectively. The accumulation urinary excretion at 48 hours post dosing were 39%±69%, 38%±7% and 36%±5%, respectively. The concentrations and AUCs of gemifloxacin had a linear pharmacokinetics with dose manner. (2) The results from multiple dosing of 320 mg for 7 days showed that the pharmacokinetic course following the last dose on day 7 was in accordance with one following the first dose on day 1, which were in accordance with the two-compartment model. The Cmax was (1.6±0.3) mg/L on day 1 and (1.6±0.3) mg/L on day 7. The mean times to reach Cmax were (0.9±0.4) and (1.1±0.3) h, respectively. The values of t1/2β were (6.1±0.8) and (7.8±0.4) h, respectively. The AUC0-∞ on day 7 was significantly higher than that on day 1 (9.40 mg·L-1·h vs 8.23 mg·L-1·h). The accumulation urinary excretion at 48 hours post dosing were 37%±5% and 42%±9%, respectively. The pharmacokinetic parameters had no statistical significance between day 1 and day 7. The mean accumulated factor of AUC on day 7 against on day 1 was 1.13±0.02, suggesting that multiple administrations of 320 mg gemifloxacin once daily for 7 days caused a mild accumulation. (3) One subject was reported with pharyngitis and 3 subjects with dizziness, diarrhea, and tremor after took single oral dose of 160 mg of gemifloxacin. There were no laboratory abnormalities except for two occurrences of slight bilirubinaemia. CONCLUSION: The results show that the pharmacokinetics of single dose and multiple dose of gemifloxacin in healthy Chinese male subjects are linear and major pharmacokinetics parameters on day 7 are similar to those following the first dose on day 1 after subjects taking multiple dosing of 320 mg once daily for 7 days. The data suggest that single and multiple doses of gemifloxacin are well tolerated except that one subject was withdrawn because of rash.
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