Pharmacokinetics of moxifloxacin, a novel 8-methoxy-quinolone, in patients with renal dysfunction.

摘要

AIMS: To evaluate the influence of impaired renal function on the plasma and urinary pharmacokinetics of moxifloxacin, a novel 8-methoxy-quinolone antibacterial drug. METHODS: Twenty male and 12 female subjects (8 healthy subjects, 24 patients with impaired renal function), 18--75 years of age were investigated in parallel fashion with four groups stratified according to creatinine clearance (CLCR; n=8 for each group). The pharmacokinetics of moxifloxacin and the metabolites M1 (sulphonate metabolite) and M2 (glucuronide) in plasma and urine were determined repeatedly up to 96 h after single oral doses of 400 mg. Patients were monitored intensively with regard to clinical and laboratory safety and tolerability. RESULTS: Single doses of 400 mg moxifloxacin were safe and well tolerated. The urinary excretion of moxifloxacin (Aeur, P: 0.0002) and renal clearance (CLR, P<0.0001) were reduced with decreasing CLCR, mean Cmax was slightly reduced (Cmax-ratio 85.0%, 90% CI 67.9, 106.4% severe renal impairment vs healthy subjects) but the AUC was unchanged even in severe renal impairment (AUC-ratio 101.3%, 90% CI 79.7, 128.6%). The mean AUC of the N-sulphonate M1 was slightly increased (by about 53% for the most severe disease) by impaired renal function, but there was no significant correlation between individual AUC and CLCR, whilst Aeur and CLR were significantly correlated with CLCR. In contrast, for the acylglucuronide M2, Aeur (P: 0.0026), CLR (P<0.0001) and AUC (P: 0.0011) were directly correlated with CLCR. CONCLUSIONS: Renal dysfunction had little effect on the plasma pharmacokinetics of either moxifloxacin or metabolite M1, although their renal clearance and urinary excretion were reduced. In contrast renal dysfunction did result in changes in the plasma pharmacokinetics of metabolite M2, causing greater and longer exposure. However the extent of these changes is unlikely to be of clinical relevance.