Document 0270
 DOCN  M9460270
 TI    Pharmacologic evaluation of megestrol acetate oral suspension in
       cachectic AIDS patients.
 DT    9408
 AU    Graham KK; Mikolich DJ; Fisher AE; Posner MR; Dudley MN; Antiinfective
       Pharmacology Research Unit, University of Rhode; Island College of
       Pharmacy, Miriam Hospital, Providence 02908.
 SO    J Acquir Immune Defic Syndr. 1994 Jun;7(6):580-6. Unique Identifier :
       AIDSLINE MED/94231462
 AB    The objective of our study was to define the pharmacokinetics and
       pharmacodynamics of megestrol acetate in patients with human
       immunodeficiency virus (HIV) infection. A new suspension formulation of
       megestrol acetate (40 mg/ml) was administered as a single oral dose of
       800 mg per day in an open label pharmacokinetic study for 21 days. On
       day 21 of therapy, patients were evaluated for changes in body weight
       and plasma samples were obtained for steady-state pharmacokinetic
       analysis. Ten HIV-infected men with an involuntary weight loss of > 10%
       baseline were evaluated. A high degree of interpatient variability in
       megestrol acetate pharmacokinetics was observed, with an 8- and 5-fold
       range in the rate and extent of absorption, respectively. All patients
       reported an increase in appetite, and 8 of 10 patients gained weight by
       3 weeks; the median change in weight in all patients at 3 weeks was
       1.8-kg gain (range: 2.3-kg loss to 6.4-kg gain). The two patients who
       did not gain weight had the lowest area under the curve (AUC), Cmax, and
       Cmin values. A statistically significant correlation between the ratio
       of body weight at 3 weeks/initial weight (weight index) and the
       percentage of the 24-h dosing interval that megestrol acetate
       concentrations exceeded a 300-ng/ml threshold was observed. These data
       indicate variable levels of systemic exposure to drug following a fixed
       dose of a suspension formulation of megestrol acetate. Increase in
       weight during the early stages of megestrol acetate therapy is related
       to the extent of in vivo drug exposure above a threshold
       concentration.(ABSTRACT TRUNCATED AT 250 WORDS)
 DE    Acquired Immunodeficiency Syndrome/*COMPLICATIONS/METABOLISM
       Administration, Oral  Adult  Appetite/DRUG EFFECTS  Body Weight/DRUG
       EFFECTS  Cachexia/*DRUG THERAPY/ETIOLOGY/METABOLISM  Human  Male
       Megestrol/*ANALOGS & DERIVATIVES/ADMINISTRATION & DOSAGE/
       PHARMACOLOGY/PHARMACOKINETICS/THERAPEUTIC USE  Middle Age  Support,
       Non-U.S. Gov't  Suspensions  JOURNAL ARTICLE

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