OBJECTIVE: To study the pharmacokinetics of zidovudine (ZDV) and its glucoronide metabolite (G-ZDV) in a patient with end-stage renal disease in haemodialysis. DESIGN: Pharmacokinetics study performed during and between haemodialysis sessions. METHODS: The patient was treated with oral ZDV (100 mg every 8 h). Concentrations of ZDV and G-ZDV were measured by radioimmunoassay. A monocompartmental model was used to calculate pharmacokinetic parameters. RESULTS: The peak plasma concentrations of ZDV and G-ZDV after drug administration between haemodialysis sessions were 0.57 and 10.01 micrograms/ml, respectively. The half-lives of ZDV and G-ZDV rose to 3.2 and 14.2 h, respectively. The total body clearance for ZDV in the period between haemodialysis sessions (0.44 l/kg/h) was 66% lower than normal values. The ZDV half-life was normalized by haemodialysis, the total body clearance of ZDV increased (1.12 l/kg/h) and the G-ZDV half-life shortened (5.9-7.9 h). Neither G-ZDV accumulation nor derived ZDV toxicity occurred. CONCLUSIONS: Our data suggest that ZDV is safe and an efficient drug when administered at a dosage of 100 mg three times daily in patients with end-stage renal disease in haemodialysis sessions, and that ZDV and G-ZDV are cleared by haemodialysis.
OBJECTIVE: To study the pharmacokinetics of zidovudine (ZDV) and its glucoronide metabolite (G-ZDV) in a patient with end-stage renal disease in haemodialysis. DESIGN: Pharmacokinetics study performed during and between haemodialysis sessions. METHODS: The patient was treated with oral ZDV (100 mg every 8 h). Concentrations of ZDV and G-ZDV were measured by radioimmunoassay. A monocompartmental model was used to calculate pharmacokinetic parameters. RESULTS: The peak plasma concentrations of ZDV and G-ZDV after drug administration between haemodialysis sessions were 0.57 and 10.01 micrograms/ml, respectively. The half-lives of ZDV and G-ZDV rose to 3.2 and 14.2 h, respectively. The total body clearance for ZDV in the period between haemodialysis sessions (0.44 l/kg/h) was 66% lower than normal values. The ZDV half-life was normalized by haemodialysis, the total body clearance of ZDV increased (1.12 l/kg/h) and the G-ZDV half-life shortened (5.9-7.9 h). Neither G-ZDV accumulation nor derived ZDVtoxicity occurred. CONCLUSIONS: Our data suggest that ZDV is safe and an efficient drug when administered at a dosage of 100 mg three times daily in patients with end-stage renal disease in haemodialysis sessions, and that ZDV and G-ZDV are cleared by haemodialysis.
Authors: Gregory M Lucas; Michael J Ross; Peter G Stock; Michael G Shlipak; Christina M Wyatt; Samir K Gupta; Mohamed G Atta; Kara K Wools-Kaloustian; Paul A Pham; Leslie A Bruggeman; Jeffrey L Lennox; Patricio E Ray; Robert C Kalayjian Journal: Clin Infect Dis Date: 2014-09-17 Impact factor: 9.079