Pharmacokinetics and saturable renal tubular secretion of zidovudine in rats

✍ Scribed by Bela A. Patel; Chung K. Chu; F. Douglas Boudinot

• Publisher: John Wiley and Sons
• Year: 1989
• Tongue: English
• Weight: 671 KB
• Volume: 78
• Category: Article
• ISSN: 0022-3549
• DOI: 10.1002/jps.2600780704

✦ Synopsis

The purpose of this study was to assess the effects of dose on the pharmacokinetics of zidovudine (3'-azido-3'-deoxythymidine; AZT) in rats. Zidovudine (AZT) was administered intravenously at doses of 10, 50, 100, and 250 mgikg. Plasma and urine AZT concentrations were determined by HPLC. Plasma AZT concentrations declined rapidly with a terminal half-life ranging from 0.76 h at a dose of 10 mg/kg to 1.58 h at 250 mgikg. Total clearance (CL,) was similar at the doses of 10 and 50 mg/kg, with values of 2.80 and 2.73 Uh/kg, respectively. However, there was a trend toward nonlinearity at the dose of 100 mg/kg (CL, = 2.13 Uhikg) and a significant decrease in CL, (1.22 Uh/kg) at the dose of 250 mgikg. Nonrenal clearance remained unaffected by dose with a mean value of 0.98 Uhikg. Renal clearance (CL,) was similar at the doses of 10 and 50 mg/kg, with values of 1.89 and 1.37 Uh/kg, respectively. However, significant decreases in CL, were observed at the