PHARMACOKINETICS OF SINGLE AND CHRONIC DOSE ZIDOVUDINE IN 2 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-mu-g/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 < 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 < 10%. The small amount of unchanged ZDV removed by CAPD suggests that no supplemental doses are needed in HIV patients undergoing CAPD.