Titre du document / Document title

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

Auteur(s) / Author(s)

SUNESEN Vibeke Hougaard ⁽¹⁾ ; VEDELSDAL Rune ⁽²⁾ ; KRISTENSEN Henning Gjelstrup ⁽¹⁾ ; CHRISTRUP Lona ⁽¹⁾ ; MÜLLERTZ Anette ⁽¹⁾ ;

Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)

⁽¹⁾ Department of Pharmaceutics, The Danish University of Pharmaceutical Sciences, Universitetsparken 2, 2100 Copenhagen, DANEMARK
⁽²⁾ Multidisciplinary Pain Centre, Copenhagen University Hospital, 2730 Herlev, DANEMARK

Résumé / Abstract

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 50 mg danazol solubilized in 40% hydroxypropyl-β-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 100 mg 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.

Revue / Journal Title

European journal of pharmaceutical sciences   ISSN 0928-0987 

Source / Source

2005, vol. 24, n^o4, pp. 297-303 [7 page(s) (article)] (28 ref.)

Langue / Language

Anglais

Editeur / Publisher

Elsevier, Shannon, IRLANDE  (1993) (Revue)

Mots-clés anglais / English Keywords

Gonadotropin ; Antagonist ; Androgen ; Pharmaceutical technology ; Gut ; Gastric emptying ; Drug ; Pharmacokinetics ; Bioavailability ; Food ; Danazol ;

Mots-clés français / French Keywords

Gonadotrophine ; Antagoniste ; Androgène ; Technologie pharmaceutique ; Intestin ; Evacuation gastrique ; Médicament ; Pharmacocinétique ; Biodisponibilité ; Aliment ; Danazol ;

Mots-clés espagnols / Spanish Keywords

Gonadotropina ; Antagonista ; Andrógeno ; Tecnología farmacéutica ; Intestino ; Vaciamiento gástrico ; Medicamento ; Farmacocinética ; Biodisponibilidad ; Alimento ; Danazol ;

Mots-clés d'auteur / Author Keywords

Danazol; Absolute bioavailability ; Gastric emptying; Small intestinal transit time; Food effect ;

Localisation / Location

INIST-CNRS, Cote INIST : 26027, 35400012631439.0050