Effect of liquid volume and food intake on the absolute bioavailability of danazol, a poorly soluble drug

TY - JOUR

T1 - Effect of liquid volume and food intake on the absolute bioavailability of danazol, a poorly soluble drug

AU - Sunesen, Vibeke Hougaard

AU - Vedelsdal, Rune

AU - Kristensen, Henning Gjelstrup

AU - Christrup, Lona

AU - Müllertz, Anette

N1 - Keywords: Adolescent; Adult; Biological Availability; Cross-Over Studies; Danazol; Dietary Fats; Drinking; Eating; Food-Drug Interactions; Gastric Emptying; Humans; Male; Solubility

PY - 2005

Y1 - 2005

N2 - 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

AB - 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

U2 - 10.1016/j.ejps.2004.11.005

DO - 10.1016/j.ejps.2004.11.005

M3 - Journal article

C2 - 15734296

SN - 0928-0987

VL - 24

SP - 297

EP - 303

JO - European Journal of Pharmaceutical Sciences

JF - European Journal of Pharmaceutical Sciences

IS - 4

ER -