Effect of erythromycin and rifampicin on monoethylglycinexylidide test

The dynamic liver function test based on the hepatic conversion of lidocaine to monoethylglycinexylidide (MEGX) provides a direct measure of the actual functional state of the liver. Cytochrome P450 (CYP) 3A4 has been proposed as the main CYP isoform responsible for MEGX formation. The concomitant use of either CYP3A4 inducer rifampicin or CYP3A4 inhibitor erythromycin may influence the results of MEGX test. Hence, the objective of this study was to evaluate the effect of a CYP3A4 inhibitor erythromycin and inducer rifampicin on the MEGX test.

The study included 20 healthy male volunteers whose routine laboratory tests were normal. As per study protocol, MEGX test was carried out in all the participants after an overnight fast. All the participants were given 1 mg/kg lidocaine dose intravenously and MEGX concentration at 30 and 60 min after IV dose was measured using HPLC. These MEGX values served as control values. Ten subjects received 600 mg/day erythromycin orally for six days while remaining ten participants received 600 mg/day rifampicin orally for six days. On the sixth day, MEGX test was carried out two hours after the last dose.

Rifampicin increased the mean plasma concentration of MEGX(30) from 93.94 ± 26.31 to 98.54 ± 24.94 μg/ml (P = 0.085) and MEGX(60) from 134.34 ± 35.42 to 136.36 ± 33.14 μg/ml (P = 0.051). Erythromycin lowered the serum concentration of MEGX(30) from 101.37 ± 39.39 to 96.67 ± 36.09 μg/ml (P = 0.128) and MEGX(60) from 142.52 ± 42.65 to 138.98 ± 40.23 μg/ml (P = 0.159).

It can be concluded from this study that the MEGX test is not affected by concomitant administration of CYP3A4 modifiers rifampicin and erythromycin.