Pharmacokinetics, Metabolism and Analgesic Effects of Flupirtine

• Status: Completed
• Trial end date: 2009-06-01
• Target enrollment: 0
• Participant gender: All

Summary

Flupirtine is metabolized in-vitro via carbamate cleavage and N acetylation to glucuronides and mercapturic acid derivatives. The formation of reactive, toxic intermediate products may be influenced by genetic polymorphisms of the involved conjugative metabolic pathways. So the purpose of this study is to measure pharmacokinetics, metabolism and analgesic effects of flupirtine in dependence on the function of NAT2, UGT1A1 and GSTP1.

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: University Medicine Greifswald
• Collaborator: AWD.pharma GmbH & Co. KG
• Treatments: Analgesics; Flupirtine

Criteria

Inclusion Criteria:

• age: 18 - 45 years

• sex and genetics: male and female genotyped for NAT2, UGT1A1 and GSTP1

• ethnic origin: Whites

• body weight: 19 - 27 kg/m²

• good health as evidenced by the results of the clinical examination, ECG, and the laboratory check-up, which are judged by the clinical investigator not to differ in a clinical relevant way from the normal state

• written informed consent

Exclusion Criteria:

• existing cardiac or hematological diseases and/or pathological findings which might interfere with safety, pharmacodynamic effect and/or pharmacokinetics of the study drug

• existing or further obstructive lung disease (e.g. bronchial asthma)

• myasthenia gravis

• existing hepatic and renal diseases and/or pathological findings which might interfere with safety, pharmacodynamic effect and/or pharmacokinetics of the study drug

• existing gastrointestinal diseases and/or pathological findings which might interfere with safety, pharmacodynamic effect and/or pharmacokinetics of the study drug

• acute or chronic diseases which could affect drug absorption or metabolism

• history of any serious psychological disorder

• drug or alcohol dependence

• positive drug screening or -only in suspicious case- positive alcohol test

• smokers of 10 or more cigarettes per day

• positive screening results for HIV, HBV and HCV

• volunteers who are on a diet which could affect the pharmacokinetics of the drug (vegetarian)

• heavy tea or coffee drinkers (more than 1l per day)

• lactation and pregnancy test positive or not performed

• volunteers suspected or known not to follow instructions

• volunteers who are unable to understand the written and verbal instructions, in particular regarding the risks and inconveniences they will be exposed to as a result of their participation in the study

• volunteers liable to orthostatic dysregulation, fainting, or blackouts

• blood donation or other blood loss of more than 400 ml within the last 12 weeks prior to the start of the study

• participation in a clinical trial during the last 3 months prior to the start of the study

• less than 14 days after last acute disease

• any systemically available medication within 4 weeks prior to the intended first administration unless, because of the terminal elimination half-life, complete elimination from the body can be assumed for the drug and/or its primary metabolites (except oral contraceptives)

• repeated use of drugs during the last 4 weeks prior to the intended first administration, which can influence hepatic biotransformation (e.g. barbiturates, cimetidine, phenytoin, rifampicin)

• repeated use of drugs during the last 2 weeks prior to the intended first administration which affect absorption (e.g. laxatives, metoclopramide, loperamide, antacids, H2-receptor antagonists)

• intake of grapefruit containing food or beverages within 7 days prior to administration

• known allergic reactions to the active ingredients used or to constituents of the pharmaceutical preparation

• subjects with severe allergies or multiple drug allergies