Pharmacokinetics of sparfloxacin in patients with renal impairment

Abstract

The pharmacokinetics of sparfloxacin were studied in 14 renal failure patients (group I, 7 with creatinine clearance of > 10 to 30 ml/min; and group II, 7 with creatinine clearance of < or = 10 ml/min) after a single oral dose of 400 mg. Plasma and urine samples were collected up to 144 h postdosing for determination of parent and total (parent-plus-glucuronide-conjugated) sparfloxacin levels, by high-pressure liquid chromatography assay and UV detection. The elimination of the drug in patients compared with that in healthy volunteers was markedly impaired. The mean elimination half-lives of sparfloxacin were 34.9 and 38.5 h in group I and group II, respectively, versus 19.1 h in healthy volunteers. Conjugated drug half-lives were 23.7, 35.0, and 15.3 h, respectively. The renal clearance of the drug was markedly reduced in the patients, with values of 6.8, 4.8, and 21.2 ml/min determined for group I, group II, and healthy subjects, respectively, for parent sparfloxacin and with values of 31.5, 14.0, and 327 ml/min for conjugated sparfloxacin. The nonrenal clearance of sparfloxacin was moderately, but not significantly, decreased in group II renal failure patients. No difference between the two groups of patients was detected in sparfloxacin levels in plasma. A significant relationship between pharmacokinetic parameters and creatinine clearance was observed only for renal clearance of parent or conjugated sparfloxacin.