CLARITHROMYCIN LOWERS PLASMA ZIDOVUDINE LEVELS IN PERSONS WITH HUMAN-IMMUNODEFICIENCY-VIRUS INFECTION

The use of antiretroviral agents and drugs for the treatment and proph ylaxis of opportunistic infections has lengthened the survival of pers ons with AIDS, In the era of multidrug therapy, drug interactions are important considerations in designing effective and tolerable regimens , Clarithromycin has had a significant impact on the treatment of diss eminated Mycobacterium avium complex infection, and zidovudine is the best-studied and one of the most widely used antiretroviral agents in this population, We conducted a study to determine the maximally toler ated dose of clarithromycin and the pharmacokinetics of clarithromycin and zidovudine individually and in combination, Mixing studies were c onducted to simulate potential interaction in the gastric environment, The simultaneous administration of zidovudine and clarithromycin had little impact on the pharmacokinetics of clarithromycin or of its majo r metabolite, However, coadministration of zidovudine and clarithromyc in at three doses (500 mg orally [p,o,] twice daily [b,i,d,], 1,000 mg p,o, b,i,d,, and 2,000 mg p,o, b,i,d,) reduced the maximum concentrat ion of zidovudine by 41% (P < 0.005) and the area under the concentrat ion-time curve from 0 to 4 h for zidovudine by 25% (P < 0.05) and incr eased the time to maximum concentration of zidovudine by 84% (P < 0,05 ), compared with zidovudine administered alone, Mixing studies did not detect the formation of insoluble complexes due to chelation, suggest ing that the decrease in zidovudine concentrations results from some o ther mechanism, Simultaneous administration of zidovudine and clarithr omycin appears to decrease the levels of zidovudine in serum, and it m ay be advisable that these drugs not be given at the same time, Drug i nteractions should be carefully evaluated in persons with advanced hum an immunodeficiency virus infection who are receiving multiple pharmac ologic agents.