ZIDOVUDINE, TRIMETHOPRIM, AND DAPSONE PHARMACOKINETIC INTERACTIONS INPATIENTS WITH HUMAN-IMMUNODEFICIENCY-VIRUS INFECTION

Zidovudine is widely prescribed for the treatment of human immunodefic iency virus (HIV) infection. Trimethoprim and dapsone are commonly use d in the management of Pneumocystis carinii pneumonia in HIV-infected patients. To examine the pharmacokinetic interactions among these drug s, eight HIV-infected patients (26 to 43 years old) with a mean CD4 co unt of 524.4 +/- 405.7 cells per mm(3) received zidovudine (200 mg), t rimethoprim (200 mg), and dapsone (100 mg) as single agents and in two - and three-drug combinations. Blood and urine samples were collected at a specified time and analyzed for zidovudine, zidovudine-glucuronid e, trimethoprim, dapsone, and monoacetyl-dapsone concentrations under single-dose and steady-state conditions. Zidovudine did not influence the pharmacokinetic disposition of dapsone or trimethoprim. Dapsone ha d no effect on the pharmacokinetic disposition of zidovudine. Trimetho prim significantly decreased the renal clearance of zidovudine by 58% (5.0 +/- 1.8 versus 2.1 +/- 0.5 ml/min/kg of body weight [P < 0.05]). There was a concurrent 54% decrease in the mean urinary recovery of zi dovudine (11.7 +/- 3.5 versus 5.4 +/- 3.0 [P < 0.05]), and the metabol ic ratio was decreased by 78% (0.32 +/- 0.4 versus 0.07 +/- 0.05 [P < 0.05]). The mean area under the concentration-time curve from 0 to 6 h of the zidovudine-glucuronide/zidovudine ratio was unchanged. We conc lude that zidovudine, trimethoprim, and dapsone can be coadministered to patients with AIDS without significant pharmacokinetic interaction. However, in AIDS patients with liver impairment and impaired glucuron idation, doses of zidovudine may need to be decreased.