Pharmacokinetics of single and chronic dose zidovudine in two HIV positive patients undergoing continuous ambulatory peritoneal dialysis (CAPD).
The effect of continuous ambulatory peritoneal dialysis (CAPD) on zidovudine (ZDV) elimination was studied in two HIV-positive men. Serum and dialysate samples were collected after a single oral dose of 200 mg (patient 1) or 100 mg (patient 2) of ZDV, and again on at least one occasion during chronic therapy (100 mg every 8 h). Concentrations of ZDV and its glucuronide metabolite (GZDV) were measured by radioimmunoassay. ZDV serum half-lives on day 1 were 7.9 h (patient 1) and 2.6 h (patient 2). The apparent GZDV half-lives on day 1 were 19.9 h (patient 1) and 7.1 h (patient 2), with resultant accumulation of metabolite (up to 36 micrograms/ml) during chronic therapy. At 14 h following single dose, 8.2 +/- 0.4% of dose was recovered in dialysate as GZDV; ZDV accounted for less than 0.6% of dose recovered in dialysate after both single and multiple dose. After the initial dwell (tau) following single dose, peritoneal clearances of ZDV were 4.3 ml/min (tau = 4 h, patient 1) and 5.9 ml/min (tau = 5 h, patient 2), and GZDV clearances were 6.7 and 5.1 ml/min, respectively. ZDV serum protein binding was less than 10%. The small amount of unchanged ZDV removed by CAPD suggests that no supplemental doses are needed in HIV patients undergoing CAPD.
Gallicano
K D
KD
Health & Welfare Canada, Bureau of Drug Research, Ottawa, Ontario.
Tobe
S
S
Sahai
J
J
McGilveray
I J
IJ
Cameron
D W
DW
Kriger
F
F
Garber
G
G
D000163:Acquired Immunodeficiency Syndrome / Q000097:blood / Q000188:drug therapy; D000284:Administration, Oral; D000328:Adult; D004334:Drug Administration Schedule; D006679:HIV Seropositivity / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood / Q000150:complications / Q000628:therapy; D008297:Male; D008875:Middle Aged; D010531:Peritoneal Dialysis, Continuous Ambulatory; D015215:Zidovudine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*
D015215:Zidovudine