Pharmacokinetics of sparfloxacin in healthy volunteers and patients: a review

In Caucasian volunteers and patients plasma sparfloxacin concentrations reached a peak of 1.2–1.5 mg/L between 3 and 6 h after a single 400 mg dose; T½ ranged from 16 to 22 h. The peak plasma concentration and the area under the plasma concentration-time curve exhibited dose-related increases but a slight decrease in the extent of absorption was observed following administration of doses above those recommended for clinical use. Renal clearance did not exceed 10% of the apparent plasma clearance. The urinary excretion of unchanged drug accounted for 9–10% of the dose administered and that of its glucuronide for 27–38% of the dose. The biliary excretion of the drug and its glucuronide accounted for about 1.5 and 11% of the dose administered, respectively. Following multiple-dose administration (200 mg daily after a loading dose of 400 mg on day 1), steady-state concentrations were achieved following the second dose. The peak plasma concentration was 1.4 mg/L and the trough concentration was 0.5 mg/L. The T½ was approximately 20 h. Studies in patients show that the pharmacokinetics of sparfloxacin were not influenced by age but severe renal failure markedly impaired elimination of the parent drug (the T½ was approximately doubled in patients with renal failure), and glucuronide, requiring adjustment of the dosage regimen. In patients with liver cirrhosis but no cholestasis, the pharmacokinetics of sparfloxacin were not markedly altered, although the urinary excretion of the glucuronide was about twice that observed in healthy volunteers. No modification of the usual dosage is recommended for these patients.