Document 0825
 DOCN  M9460825
 TI    Effect of metoclopramide and loperamide on the pharmacokinetics of
       didanosine in HIV seropositive asymptomatic male and female patients.
 DT    9404
 AU    Knupp CA; Milbrath RL; Barbhaiya RH; Department of Metabolism and
       Pharmacokinetics, Bristol-Myers; Squibb Company, Syracuse, New York.
 SO    Eur J Clin Pharmacol. 1993;45(5):409-13. Unique Identifier : AIDSLINE
       MED/94155927
 AB    The pharmacokinetics of orally-administered didanosine were evaluated in
       6 male and 6 female HIV seropositive patients to determine the effect of
       pretreatment with metoclopramide, an inducer of gastrointestinal
       motility, and loperamide, which retards motility. Using a randomized,
       balanced, crossover design, each patient received the following three
       treatments under fasting conditions: didanosine as a single agent,
       didanosine 5 min after a single 10 mg intravenous dose of
       metoclopramide, and didanosine 1 h after the final of 4 doses, 4 mg
       each, of loperamide. Serial blood and urine samples were collected for
       up to 12 h after each dose. Plasma and urine aliquots were analysed for
       intact didanosine using HPLC with UV detection. Pharmacokinetic
       parameter values were calculated using noncompartmental methods. The
       mean Cmax values were significantly greater for the didanosine single
       agent (2.04 micrograms.ml-1) and didanosine with metoclopramide (2.30
       micrograms.ml-1) treatments than for the combination of didanosine with
       loperamide (1.57 microgram.ml-1). The t1/2 in males was significantly
       greater than in females for the didanosine (1.75 vs 1.12 h,
       respectively) and didanosine with metoclopramide treatments (1.74 vs
       1.20 h, respectively). No significant treatment or gender effects were
       observed for AUC or UR (urinary recovery). The pharmacokinetics of
       didanosine were not altered appreciably by dosing with metoclopramide.
       Administration with loperamide affected the rate but not the extent of
       absorption. There were no clinically relevant differences between males
       and females in the disposition of didanosine.
 DE    Administration, Oral  Comparative Study
       Didanosine/BLOOD/*PHARMACOKINETICS/URINE  Female  Human  HIV
       Seropositivity/*METABOLISM  Loperamide/ADMINISTRATION &
       DOSAGE/*PHARMACOLOGY  Male  Metoclopramide/ADMINISTRATION &
       DOSAGE/*PHARMACOLOGY  CLINICAL TRIAL  JOURNAL ARTICLE  RANDOMIZED
       CONTROLLED TRIAL

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