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 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). 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.
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 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). 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.
Authors: S Imaoka; K Enomoto; Y Oda; A Asada; M Fujimori; T Shimada; S Fujita; F P Guengerich; Y Funae Journal: J Pharmacol Exp Ther Date: 1990-12 Impact factor: 4.030