Objective:To determine whether diarrhea and intestinal malabsorption during HIV infection alter oral ganciclovir systemic exposure.
Methods:We studied the oral disposition of ganciclovir in 42 HIV-infected patients stratified into three groups: A (n = 15), HIV (stage A and B); B (n = 13), AIDS (stage C); and C (n = 14), AIDS with chronic diarrhea and wasting syndrome (10% or more weight loss). Each patient was evaluated for nutritional (body mass index, serum albumin and transferrin), immunologic (CD4 count, plasma viral load) and intestinal status (D-xylose test, fecal fat and nitrogen excretion, and intestinal permeability). Following an overnight fast, 1 g oral ganciclovir was given to patients. Six blood samples were collected over 24 hours. Serum was analyzed for ganciclovir by high performance liquid chromatography. Drug disposition was characterized using a population pharmacokinetic approach.
Results:Mean intestinal permeability increased as HIV disease progressed (0.05, 0.1, and 0.2 for groups A, B, and C, respectively). Average weight-adjusted maximum concentration (Cmax) in group C was twofold more than that in group A and B patients (12.5 versus 6 and 6.4 ng/ml/kg), and average area under the curve (AUC0-∞) was threefold greater in group C patients (193 versus 59 and 65 ng · hour/ml/kg in groups A and B, respectively). Mean oral clearance was threefold lower in group C (96 versus 258 and 212 L/hour in groups A and B, respectively).
Conclusion:Because systemic exposure of oral ganciclovir is enhanced in AIDS patients with diarrhea and wasting syndrome, oral ganciclovir therapy may benefit these patients.
Address correspondence and reprint requests to Stephane Mouly, General Clinical Research Center, The University of North Carolina, Campus Box #7600, Room 3005 APCF, Chapel Hill, NC 27599-7600, U.S.A.; email: email@example.com.
Manuscript received January 2, 2000; accepted May 4, 2000.
© 2000 Lippincott Williams & Wilkins, Inc.