Pharmacokinetics of T-2588 in patients with impaired renal functions

Abstract

The pharmacokinetics of T-2525, an active form of a new oral cephem antibiotic T-2588, were studied in 4 healthy volunteers and 14 patients with various degrees of renal impairment after a single oral administration of 100 mg dose of T-2588. The endgeneous creatinine clearances (Ccr) of each subject were used as indicator of renal function. Pharmacokinetic parameters were obtained following the one-compartment open model with lag phase in the absorption. The peak concentrations of T-2525 in serum were achieved 4 hours after administration without relation to the renal functions. The serum concentration of T-2525 increased in patients having the level of Ccr of 20 to 30 ml/min. The mean serum half-life of T-2525 was calculated for 0. 83±0. 02 hour in normal subjects and increased in patients along with increasing impairment of renal function. The excretion rate constant well correlated with Ccr (r = 0.739, p<0. 005). In normal subjects, 22.2±1.9% of the drug was excreted in the urine as T-2525 within the first 8 hours, and the urinary excretion rate declined gradually in patients as a degree of renal impairment advanced. In the patients with severely impaired renal function (Ccr of 20 to 30 ml/min), the drug accumulation should be predicted by giving 100 mg oral dose of T-2588 repeated at interval of 8 hours, but not in patients who have the level of Ccr of 40 to 70 ml/min. © 1986, Japanese Society of Chemotherapy. All rights reserved.