The lignocaine metabolite (MEGX) liver function test and P-450 induction in humans

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 [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-l 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 internal: - 3 to 44 μg l-1) (P = 0.55). 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.