PHARMACOKINETICS OF CLARITHROMYCIN AND ZIDOVUDINE IN PATIENTS WITH AIDS

The interrelationships between the pharmacokinetics of zidovudine alon e and of zidovudine plus clarithromycin were evaluated with 18 volunte ers with AIDS who had no infection with Mycobacterium avium complex or clinical evidence of gastroenteritis. Patients received 200 mg of zid ovudine orally every 8 h on days 1 to 4 and 1,000 mg of clarithromycin every 12 h, given 2 h apart from zidovudine, on days 2 to 4. Concentr ations of zidovudine in plasma were measured at steady state both prio r to (phase 1, day 1) and during (phase 2, day 4) administration of cl arithromycin, Levels of clarithromycin were measured at steady state o n day 4. The maximum concentrations of zidovudine in plasma were signi ficantly different in phases 1 and 2 (616.6 and 949.0 ng/ml, respectiv ely), as were the times to the maximum concentrations of zidovudine (2 .1 and 1.0 h, respectively). However, the minimum concentrations in pl asma and the areas under the concentration-time curves from 0 to 6 h d id not differ on days 1 and 4. There is no significant impact on the o verall bioavailability of zidovudine from the addition of clarithromyc in in patients with AIDS. Clarithromycin may increase the rate of zido vudine absorption, but this is unlikely to have clinical relevance.