Pharmacokinetics, Metabolism and Analgesic Effects of Flupirtine

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.

Conditions

• Pain
• Pharmacokinetics
• Flupirtine

Interventions

DRUG

100 mg flupirtine intravenous

Administration of 100 mg flupirtine intravenous (3 mg solution intravenously, 1 vial Kadadolon® inject)

DRUG

100 mg flupirtine per os

Administration of 100 mg flupirtine per os (1 capsule Kadadolon®)

DRUG

400 mg flupirtine per os

Administration of 400 mg flupirtine (1 Kadadolon® S long retard tablet)

PROCEDURE

induce delayed onset of muscle soreness (DOMS)

The DOMS exercise protocol consists of two sets of 50 concentric/eccentric contractions of the calf muscles of one leg with a rest of 5 min in-between. The exercise is performed 22-26 h prior to medication. For pain measurements, muscle pain is stimulated by standing on tiptoes of one leg for 30 s, which requires a constriction of the affected calf muscles. The other leg is lifted and the subjects are allowed to hold on to a table to keep their balance. The pain intensity during this stimulation is then rated by means of a 10 cm visual analogue scale (VAS). The VAS is extended from "no pain" to "intolerable pain" with a precision of 1 mm. The stimulation is repeated with the other leg. The sequence of the legs is chosen randomly.

PROCEDURE

electric pain measurement

The method has been described to be sensitive to quantify analgesic opioid effects. Painful 5 Hz sine waves electrical stimuli (increase of intensity 0.2 mA/s, from 0 to 20 mA), which predominantly activate C-fibres, will be applied via two gold electrodes placed on the medial and lateral side of the distal phalangeal joint (middle finger of the left hand as default-testing site). During testing, subjects keep a button continuously pressed until they find the pain intolerably and interrupt the current by releasing the button. The electrical current at which this occurred is defined as pain tolerance, the target parameter of this pain model. Each value of pain tolerance is the median of five subsequent measurements obtained at an interval of 1 min.

Sponsors & Collaborators

• AWD.pharma GmbH & Co. KG

  collaborator UNKNOWN

• University Medicine Greifswald

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

NONE

Model

CROSSOVER

Eligibility

Min Age

18 Years

Max Age

45 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2008-05-31

Primary Completion

2009-05-31

Completion

2009-06-30

Countries

• Germany

Study Locations