Abstract
The pharmacokinetics of cefsulodin were characterized in 19 patients with different degrees of renal function after a single 500-mg, 30-min intravenous infusion. Six subjects had a creatinine clearance (Clcr) of greater than 100 ml min-1 (group I), eight had a Clcr of between 12 and 42 ml min-1 (group II), and five had a Clcr of less than 10 ml min-1 (group III). Nine plasma and four urine samples were collected in the first 36 h. The plasma concentration-time data were fitted to a two-compartment open model. The mean beta-phase half-life was 1.77, 6.37, and 10.12 h in groups I, II, and III, respectively. A significant decline in plasma clearance (Clp) was also noted between the three groups: 136 to 49.6 to 27.2 ml min-1 in groups I, II, and III, respectively. Steady-state volume of distribution was 0.26 liter kg-1, regardless of renal function. The observed linear relationship between Clp and Clcr (Clp = 24.09 + 0.765 Clcr; r = 0.9566) can be utilized to revise dosage schedules for patients with any degree of renal impairment. The nonrenal clearance of cefsulodin was also noted to be significantly lower in groups II and III than in group I. Further investigations will be necessary to elucidate the mechanism(s) responsible for the decrease in the nonrenal clearance of cefsulodin.
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Selected References
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