       Document 0742
 DOCN  M9620742
 TI    Ganciclovir absolute bioavailability and steady-state pharmacokinetics
       after oral administration of two 3000-mg/d dosing regimens in human
       immunodeficiency virus- and cytomegalovirus-seropositive patients.
 DT    9602
 AU    Anderson RD; Griffy KG; Jung D; Dorr A; Hulse JD; Smith RB; Novum, Inc.,
       Pittsburgh, Pennsylvania, USA.
 SO    Clin Ther. 1995 May-Jun;17(3):425-32. Unique Identifier : AIDSLINE
       MED/96070351
 AB    Oral ganciclovir has recently been approved for use in long-term
       maintenance therapy in the treatment of cytomegalovirus (CMV) retinitis
       in immunocompromised patients. Although oral ganciclovir at a dose of
       3,000 mg/d is moderately less effective than intravenous (i.v.)
       ganciclovir maintenance therapy (5 mg/kg as a 1-hour i.v. infusion every
       24 hours), convenience and practicality make oral maintenance therapy
       desirable. Two dosing regimens--1,000 mg three times daily (TID) and 500
       mg every 3 hours (six times daily)--have been shown to be efficacious.
       Eighteen human immunodeficiency virus- and CMV-seropositive patients
       participated in a three-way, open-label, crossover study to evaluate the
       steady-state pharmacokinetics and absolute bioavailability of the two
       oral regimens compared with the i.v. regimen. Sixteen patients completed
       the study and received ganciclovir as a single 5-mg/kg i.v. infusion
       over 1 hour, 500 mg orally every 3 hours while awake (six times daily)
       for 3 days, and 1,000 mg TID orally for 3 days. Blood samples were
       obtained over a 24-hour period after the single i.v. dose and on day 3
       of the oral dosing regimens. Mean peak serum concentrations were 8.27,
       1.02, and 1.18 micrograms/mL for the i.v. and oral regimens,
       respectively. Twenty-four-hour area under the curve (AUC) for the oral
       regimens--500 mg every 3 hours and 1,000 mg TID--were 15.9 and 15.4
       micrograms.h/mL, respectively, as compared with a total AUC of 22.1
       micrograms.h/mL for the single i.v. dose. The absolute bioavailabilities
       for the two oral regimens were 8.84% and 8.53%, respectively. The extent
       of ganciclovir absorption, peak concentrations, and average
       concentration at steady state were not statistically different between
       the two oral regimens. The peak-to-trough concentration ratio
       (Cmax:Cmin) was greater for the 1,000-mg TID regimen than for the
       regimen of 500 mg every 3 hours (5.35 vs 3.81 [P < 0.01]). Both oral
       regimens resulted in concentrations in the range of the concentration
       that inhibits 50% of most human CMV isolates. Because both oral regimens
       provide equivalent absorption, the 1,000-mg TID regimen may be preferred
       for the convenience and potentially greater compliance associated with
       fewer daily doses.
 DE    Administration, Oral  Adult  Antiviral Agents/ADMINISTRATION &
       DOSAGE/*PHARMACOKINETICS  Biological Availability  Comparative Study
       Cross-Over Studies  Cytomegalovirus Infections/*METABOLISM  Female
       Ganciclovir/ADMINISTRATION & DOSAGE/*PHARMACOKINETICS  Human  HIV
       Seropositivity/*METABOLISM  Infusions, Intravenous  Male  CLINICAL TRIAL
       JOURNAL ARTICLE  RANDOMIZED CONTROLLED TRIAL

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

