Tolerability and pharmacokinetics of antofloxacin hydrochloride after multiple oral dose administration in healthy Chinese male volunteers.

OBJECTIVE

To evaluate the tolerability and pharmacokinetics characteristics of antofloxacin hydrochloride, a fluoroquinolone developed in China, after multiple oral doses in healthy male Chinese volunteers.

METHODS

13 subjects took 300 mg of antofloxacin hydrochloride once daily for 7 days. Safety was evaluated on Days 0, 2, 4 and 8. Blood and urine samples for pharmacokinetics analysis were taken at designated time points. HPLC was used to assay the serum and urine concentration of antofloxacin.

RESULTS

A total of 12 subjects completed the trial and 1 volunteer was dropped because of a skin rash 2 h after the drug was administered. 1 volunteer had a prolonged prothrombin time (PT), another had a serum alanine aminotransferase (ALT) elevation and a third had increases in aspartate aminotransferase (AST) and I(3)-glutamyltransferase (I(3)-GT). No other complaints were reported during the trial. The steady state serum concentration on a daily 300 mg oral dose was obtained at 96 h. The pharmacokinetics parameters at steady state were: t(max)1.19 A+/- 0.59 h, C(max) 4.49 A+/- 0.81 mg/l, C(min) 1.35 A+/- 0.33 mg/l, AUC(ss) 74.74 A+/- 12.58 mg/l A h, C(av) 3.11 A+/- 0.52 mg/l, t(1/2beta) 20.75 A+/- 2.93 h, PTF 102.13 A+/- 23.92%. The urinary elimination of antofloxacin over 120 h after the last dose was approximately 62%. C(max) in steady state was 50% higher compared to data for Day 1 after a single dose administration.

CONCLUSIONS

The results indicated that 300 mg antofloxacin hydrochloride once daily oral administration is safe, but can lead to high drug concentrations. This should be evaluated further.