Zidovudine pharmacokinetics in five HIV seronegative patients undergoing continuous ambulatory peritoneal dialysis.
A few reports in the literature describe zidovudine (AZT) pharmacokinetics in patients undergoing hemodialysis; however, the effect of continuous ambulatory peritoneal dialysis (CAPD) on the drug's disposition has not been studied. The pharmacokinetics of AZT were evaluated in five patients, age 37-62 years, who were seronegative for the human immunodeficiency virus and were undergoing CAPD. Serial plasma, urine, and dialysate samples were collected after oral administration of AZT 200 mg. Samples were assayed using radioimmunoassay (RIA). Model-independent analysis was used to determine total plasma clearance, apparent volume of distribution, mean residence time, and half-life. Net peritoneal dialysis clearance was calculated to measure the effect of CAPD on AZT disposition. We found wide interpatient variability in AZT pharmacokinetics. Peak serum concentrations ranged from 0.3-47.8 microns and area under the curve from 0.5-26.1 mg x hour/L. These differences resulted in corresponding differences in clearance (range 66-3176 ml/min/1.73 m2) and volume of distribution (range 16-825 L). Interpatient variability in glucuronidation may partially account for this variability. Net peritoneal dialysis clearance of AZT was 5 ml/minute. Although the effect of peritoneal dialysis on AZT disposition was negligible, clinicians should be aware of the large differences in the way in which individual patients with renal dysfunction handle this drug.
Kremer
D
D
Department of Medicine, Oregon Health Sciences University, Portland 97201-3098.
Munar
M Y
MY
Kohlhepp
S J
SJ
Swan
S K
SK
Stinnett
E A
EA
Gilbert
D N
DN
Young
E W
EW
Bennett
W M
WM
D000284:Administration, Oral; D000328:Adult; D015314:Dialysis Solutions / Q000378:metabolism*; D006679:HIV Seropositivity / Q000150:complications / Q000378:metabolism*; D006801:Humans; D007674:Kidney Diseases / Q000150:complications / Q000378:metabolism / Q000628:therapy; D008297:Male; D008875:Middle Aged; D010531:Peritoneal Dialysis, Continuous Ambulatory; D015203:Reproducibility of Results; D015215:Zidovudine / Q000031:analogs & derivatives / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine
D015314:Dialysis Solutions; D015215:Zidovudine; C055886:3'-azido-3'-deoxy-5'-O-beta-glucopyranuronosylthymidine