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