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


CONCLUSIONS
Because systemic exposure of oral ganciclovir is enhanced in AIDS patients with diarrhea and wasting syndrome, oral ganciclovir therapy may benefit these patients.
Mouly
S
S
Department of Internal Medicine, Lariboisiere Hospital; and Laboratory of Pharmacology, La Salpétrière Hospital, Paris, France. smouly@email.unc.edu
Aymard
G
G
Diquet
B
B
Caulin
C
C
Bergmann
J F
JF
D000284:Administration, Oral; D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D001682:Biological Availability; D018791:CD4 Lymphocyte Count; D003967:Diarrhea / Q000150:complications / Q000378:metabolism; D005260:Female; D015774:Ganciclovir / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism*; D019247:HIV Wasting Syndrome / Q000150:complications / Q000378:metabolism; D006801:Humans; D007408:Intestinal Absorption; D008297:Male; D008875:Middle Aged; D009752:Nutritional Status; D010539:Permeability; D015431:Weight Loss
D000998:Antiviral Agents; D015774:Ganciclovir