Bioavailability Of Flucloxacillin Capsules (250 mg and 500 mg)

Study Overview
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Brief Summary
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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.

Detailed Description
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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

Official Title
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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

Conditions
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Infections, Bacterial

Intervention / Treatment
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* Drug: flucloxacillin 250 mg
* Drug: flucloxacillin 500 mg


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Subjects receiving flucloxacillin 250 mg<br>Subjects will be randomized to receive single oral dose of 250 mg flucloxacillin capsule and 250 mg Intravenous dose | Drug: flucloxacillin 250 mg<br>* Subjects will be randomized to receive single oral dose of 250 mg flucloxacillin capsule and 250 mg Intravenous dose<br>* Other names: flucloxacillin;|
| Experimental: Subjects receiving flucloxacillin 500 mg<br>Subjects will be randomized to receive single oral dose of 500 mg flucloxacillin capsule and 500 mg Intravenous dose | Drug: flucloxacillin 500 mg<br>* Subjects will be randomized to receive single oral dose of 500 mg flucloxacillin capsule and 500 mg Intravenous dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute (Abs.) bioavailability, max. plasma conc., concentration-time curve (AUC) from 0 hto the last quantifiable conc., AUC from 0 h to infinity), timepoint of max. plasma conc., Halflife of drug elimination during the terminal phase |  | Up to 60 Days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Elimination rate constant, total Clearance, Volume of distribution at steady state, Volume of distribution during the terminal phase, residual area |  | Up to 60 Days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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bioavailability flucloxacillin