bioavailability of flucloxacillin capsules (250 mg and 500 mg)

Conditions: Infections, Bacterial

Summary: primary objective:to study the absolute bioavailability, distribution and elimination parameters of flucloxacillin from two oral formulations of flucloxacillin in healthy male and/or female subjects.

a mono-center, open, randomized, three-way, twelve-sequence, cross-over study to determine the extent of absorption (absolute bioavailability), rate of absorption and to further characterize distribution and elimination characteristics of a commercial 250 mg and a 500 mg capsule of flucloxacillin each given as a single oral dose vs. one 250 or 500 mg intravenous dose to 24 healthy male and/or female subjects in the fasting state

Eligibility criteria:
inclusion criteria: * healthy volunteers, * caucasians, * body mass index (bmi) between 19 and 27 kg/m 2; * physically and mentally healthy as judged by means of a medical and standard lab examination; * non-smokers, * ex-smokers or moderate smoker. exclusion criteria: * medical history, * vital signs, * physical examination,laboratory tests (blood and/or urine) with evidence of clinically significant conditions; * 12-lead electrocardiogram (ecg) with clinically significant abnormality;acute infection within 2 weeks preceding 1st study drug administration;any medication on a regular basis (exception females: oral contraceptives) and/or tricyclic antidepressants, antacids, histamine h2-receptor antagonists, antibiotics, * non steroid anti-inflammatory drugs or anticoagulants within 8 weeks before the 1st study drug administration and/or no agreement to take any of those drugs including over-the-counter (otc) drugs until the end of the follow- up examination; * no agreement not to take any medication,including otc medicine, antacids, or analgesics within 2 weeks before 1st drug administration until the end of the follow-up examination;special diet or loss of \> 5 kg within last month from a weight reduction diet; regularly consume of large quantities of alcohol (\> 20g/day) and/or beverages containing methylxanthines e.g. caffeine (\> 0.5l/day altogether); * no agreement not to consume: - any beverages or foods containing alcohol 48 h prior to 1st study drug administration until end of the follow-up examination; * any grapefruit products 7 days prior 1st study drug administration until end of the follow-up examination, * any beverages or foods containing methylxanthines as well as fruit-juices and any foods containing poppy seed 48 h before 1st drug administration of either study period until last blood sample of the respective study period was collected, * not to consume chewing during confinement; * history of: - allergy to flucloxacillin, * b-lactams and/or related drugs, * known hypersensitivity against the inactive ingredients of the study medication, * hypersensitivity to multiple drugs, * allergic diseases, * acute hay fever, * previous history of flucloxacillin-associated jaundice/hepatic dysfunction, * alcohol or drug abuse, * epilepsy or other seizure, * psychiatric illness, e.g. latent or manifest depression schizophrenia, or neurosis, * respiratory diseases, * surgery of the gastrointestinal tract (except appendectomy), * kidney diseases, * bleeding/coagulation disorder or severe anaemia, * glucose-6-phosphate dehydrogenase deficiency and/or chronic treatment or chronic pathology; * metabolic disease; * evidence for disorder in the metabolism of pharmaceuticals or other foreign compounds; cardiovascular diseases e.g. hypertension, hypotension or bradycardia; * associated disease that would interfere with the clinical course of the trial; * major illness during 3 month before commencement of the screening period, * gastrointestinal diseases; * reported or positive results from test of drugs of abuse (amphetamines, opiates, barbiturate, methadone, cannabinoids, cocaine, benzodiazepines); * positive test for: alcohol, hepatitis-b-antigen or hepatitis-c-antibody, hiv-antibody;blood donor or blood loss including plasmapheresis within the last 3 months before the 1st study drug administration; * intake of depot injectable solutions (including study medication) within 6 month before 1st study administration; * intake of enzyme-inducing and/or organotoxic drugs within 4 weeks before 1st study drug administration;for females only: positive results from pregnancy tests;does not use or not agree to use adequate contraceptive methods during the study; * lactating woman.

Keywords: bioavailability flucloxacillin