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The lignocaine metabolite (MEGX) liver function test and P‐450 induction in humans
Author(s) -
Reichel Christoph,
Skodra Thorsten,
Nacke Axel,
Spengler Ulrich,
Sauerbruch Tilman
Publication year - 1998
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1046/j.1365-2125.1998.00829.x
Subject(s) - medicine , cyp3a4 , metabolite , pharmacokinetics , rifampicin , confidence interval , lidocaine , plasma concentration , anesthesia , gastroenterology , metabolism , cytochrome p450 , pathology , tuberculosis
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 [MEGX 30min ] 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 MEGX 30min 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.