Oral ganciclovir systemic exposure is enhanced in HIV-infected patients with diarrhea and weight loss

Objective: To determine whether diarrhea and intestinal malabsorption durin g 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 wa sting syndrome (10% or more weight loss). Each patient was evaluated for nu tritional (body mass index, serum albumin and transferrin), immunologic (CD 4 count, plasma viral load) and intestinal status (D-xylose test, fecal fat and nitrogen excretion, and intestinal permeability). Following an overnig ht fast, 1 g oral ganciclovir was given to patients. Six blood samples were collected over 24 hours. Serum was analyzed for ganciclovir by high perfor mance liquid chromatography. Drug disposition was characterized using a pop ulation 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-ad justed maximum concentration (Cmax) in group C was twofold more than that i n group A and B patients (12.5 versus 6 and 6.4 ng/ml/kg), and average area under the curve (AUC(0-x)) was threefold greater in group C patients (193 versus 59 and 65 ng . hour/ml/kg in groups A and B, respectively). Mean ora l 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 AI DS patients with diarrhea and wasting syndrome, oral ganciclovir therapy ma y benefit these patients.