title: Oral ganciclovir systemic exposure is enhanced in HIV-infected patients with diarrhea and weight loss.
abstract: 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.
authors.affiliation: Department of Internal Medicine, Lariboisiere Hospital; and Laboratory of Pharmacology, La Salpétrière Hospital, Paris, France. smouly@email.unc.edu
authors.forename: S
authors.initials: S
authors.lastname: Mouly
authors.forename: G
authors.initials: G
authors.lastname: Aymard
authors.forename: B
authors.initials: B
authors.lastname: Diquet
authors.forename: C
authors.initials: C
authors.lastname: Caulin
authors.forename: J F
authors.initials: JF
authors.lastname: Bergmann
mesh_terms: 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
chemical_list: D000998:Antiviral Agents; D015774:Ganciclovir