The lignocaine metabolite (MEGX) liver function test and P-450 induction in humans.
OBJECTIVE
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 6beta-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+/-2ml min(-1) kg(-1) (P=0.026) after induction. The normalised MEGX30min concentrations increased from 61+/-14 (day 7) to 82+/-34 microg l(-1) (day 14) by a mean of 21 microg l(-1) (95% confidence interval: -3 to 44 microg l(-1)) (P=0.055).


CONCLUSIONS
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.
Reichel
C
C
Department of General Internal Medicine, University of Bonn, Germany.
Skodra
T
T
Nacke
A
A
Spengler
U
U
Sauerbruch
T
T
D000328:Adult; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis* / Q000378:metabolism; D004790:Enzyme Induction; D006801:Humans; D008012:Lidocaine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000032:analysis / Q000097:blood / Q000493:pharmacokinetics*; D008111:Liver Function Tests / Q000379:methods*; D008297:Male; D006899:Mixed Function Oxygenases / Q000096:biosynthesis* / Q000378:metabolism; D015203:Reproducibility of Results; D012293:Rifampin / Q000494:pharmacology
D003577:Cytochrome P-450 Enzyme System; D008012:Lidocaine; C001173:monoethylglycinexylidide; D006899:Mixed Function Oxygenases; C104464:CYP3A protein, human; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D012293:Rifampin