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

Aims The N-deethylation of lignocaine to monoethylglycinexylidide (MEGX) is partially catalysed by the rifampicin inducible P-450 isoenzyme CYP3A4. Th is 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 d ays, resulting in a four- to sixfold increase in urinary 6 beta-hydroxycort isol 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 conc entrations at 30 min [MEGX(30min)] were assessed and normalised to MEGX tes t 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 in duction with rifampicin were compared. Results The li,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, T he normalised MEGX(30min) concentrations increased from 61+/-14 (day 7) to 82+/-34 mu g l(-1) (day 14) by a mean of 21 mu g l(-1) (95% confidence inte rval: -3 to 44 mu g l(-1)) (P=0.055). Conclusion An insignificant increase of MEGX plasma concentrations was foun d in 10 volunteers after induction of CYP3A4 activity by rifampicin. Theref ore, the MEGX test is not a sensitive marker of P-450 induction in healthy human liver.