Effect of liquid volume and food intake on the absolute bioavailability of danazol, a poorly soluble drug.
The influence of liquid intake and a lipid-rich meal on the bioavailability of a lipophilic drug was investigated. Danazol was used as the model substance. In a randomized four-way crossover study eight healthy male volunteers received four different treatments with danazol at 2-week intervals following an overnight fast (one I.V. infusion and three oral treatments). The I.V. formulation contained 50mg danazol solubilized in 40% hydroxypropyl-beta-cyclodextrin. The oral treatments were a Standard treatment, a Standard + 800 ml water treatment and a Standard + lipid-rich meal treatment. The Standard oral treatment consisted of 200 ml water and one capsule containing 100mg danazol, three 500 mg paracetamol tablets and two 500 mg sulfasalazine tablets. Paracetamol and sulfasalazine were used as markers for gastric emptying and small intestinal transit times. Intake of danazol with a lipid-rich meal or extra 800 ml water increased the bioavailability by 400 and 55%, respectively. Gastric emptying times increased in the following order: Standard<Standard + 800 ml water<Standard + lipid-rich meal. The effects of food and liquid on danazol bioavailability can at least partly be explained by a delay in the gastric emptying time.
Sunesen
Vibeke Hougaard
VH
Department of Pharmaceutics, The Danish University of Pharmaceutical Sciences, Universitetsparken 2, DK-2100 Copenhagen O, Denmark.
Vedelsdal
Rune
R
Kristensen
Henning Gjelstrup
HG
Christrup
Lona
L
Müllertz
Anette
A
D000293:Adolescent; D000328:Adult; D001682:Biological Availability; D018592:Cross-Over Studies; D003613:Danazol / Q000097:blood* / Q000493:pharmacokinetics; D004041:Dietary Fats / Q000493:pharmacokinetics*; D004326:Drinking / Q000502:physiology*; D004435:Eating / Q000502:physiology*; D018565:Food-Drug Interactions / Q000502:physiology*; D005746:Gastric Emptying / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008297:Male; D012995:Solubility
D004041:Dietary Fats; D003613:Danazol