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Absolute Bioavailability and Dose Proportionality of Oral Ganciclovir after Ascending Multiple Doses in Human Immunodeficiency Virus (HIV)‐Positive Patients
Author(s) -
Jung Donald,
Griffy Kay,
Wong Rodney,
Colburn Wayne,
Hulse Jim
Publication year - 1998
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/009127009803801206
Subject(s) - ganciclovir , pharmacokinetics , regimen , medicine , bioavailability , crossover study , dose , pharmacology , human cytomegalovirus , gastroenterology , placebo , virus , immunology , alternative medicine , pathology
This study was designed to determine the bioavailability and dose linearity and proportionality of ganciclovir after multiple oral administrations of 3,000 mg to 6,000 mg per day. In an open‐label, randomized, four‐treatment crossover design, 24 patients seropositive for human immunodeficiency virus (HIV) and cytomegalovirus (CMV) received in random order multiple oral doses of ganciclovir 1,000 mg every 3 hours (six times a day), 1,000 mg four times a day, and 1,000 mg three times a day and a single 5‐mg/kg intravenous infusion (over 1 hour) of ganciclovir. Blood samples for pharmacokinetic determinations were obtained on day 3 of each oral regimen and on the day of the intravenous infusion over a 24‐hour time interval. Mean steady‐state average serum concentrations of ganciclovir were 0.54, 0.79, and 0.99 μg/mL, respectively, with the 3, 4, and 6 g/day oral regimens. The steady‐state area under the concentration‐time curve (AUC 0–24 ) for the 6,000 mg/day oral regimen approached that of the single‐dose intravenous regimen. There was a proportional increase in AUC 0–24 between the 3 and 4 g/day dosage regimens, but not between the 4 and 6 g/day regimens. This suggests nonlinear absorption of ganciclovir at higher dosages, although the departure from proportionality was less than 11%.