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- Title
The lignocaine metabolite (MEGX) liver function test and P-450 induction in humans.
- Authors
Reichel, Christoph; Skodra, Thorsten; Nacke, Axel; Spengler, Ulrich; Sauerbruch, Tilman; Reichel
- Abstract
Aims The N-deethylation of lignocaine to monoethylglycinexylidide (MEGX) is partially catalysed by the rifampicin inducible P-450 isoenzyme CYP3A4. This has led to the use of the MEGX test (MEGX plasma concentrations after i.v. lignocaine) as a marker of CYP3A4 activity. To test this hypothesis, we studied lignocaine and MEGX plasma pharmacokinetics. Methods Ten healthy volunteers received rifampicin (600 mg day-1 ) for 6 days, resulting in a four- to sixfold increase in urinary 6β-hydroxycortisol output. On days 1 and 7 (pretreatment), day 11 (treatment), and day 14 (48 h after rifampicin), 50 mg lignocaine i.v. was administered. MEGX concentrations at 30 min [MEGX30min] were assessed and normalised to MEGX test results after 1 mg kg-1 lignocaine. On days 7 and 14 the lignocaine and MEGX plasma concentrations were measured over a 300 min period. MEGX test results and lignocaine and MEGX plasma pharmacokinetics before and after induction with rifampicin were compared. Results The lignocaine plasma clearance increased from 7.5±1.2 ml min-1 kg-1 before to 8.6±2 ml min-1 kg-1 (P=0.026) after induction. The normalised MEGX30min concentrations increased from 61±14 (day 7) to 82±34 μg l-1 (day 14) by a mean of 21 μg l-1 (95% confidence interval: -3 to 44 μg l-1 ) (P=0.055). Conclusion An insignificant increase of MEGX plasma concentrations was found in 10 volunteers after induction of CYP3A4 activity by rifampicin. Therefore, the MEGX test is not a sensitive marker of P-450 induction in healthy human liver.
- Subjects
LIDOCAINE; GLYCOLS; PHARMACOKINETICS
- Publication
British Journal of Clinical Pharmacology, 1998, Vol 46, Issue 6, p535
- ISSN
0306-5251
- Publication type
Article
- DOI
10.1046/j.1365-2125.1998.00829.x