Correlation between midazolam and lignocaine pharmacokinetics and MEGX formation in healthy volunteers

摘要: Aims  The objectives of the present investigation were: (a) to determine correlation between lignocaine and midazolam pharmacokinetics following intravenous administration in healthy volunteers, (b) effects treatment with an inhibitor CYP3A4 (erythromycin) on this (c) assess precision MEGX-test as a sole predictor pharmacokinetics. Methods  study was conducted four male female aged 21 26 years, who received 1 mg kg−1 HCl i.v. days 1, 3, 5, 9 10 investigation. On 5 they also midazolam, 0.075 mg kg−1 from 6–10 took erythromycin 500 mg orally, times daily. Following frequent venous blood samples were obtained for determination concentrations lignocaine, MEGX midazolam. Results  In absence statistically significant linear observed clearance (CLmidazolam= 0.41×CLlignocaine+1.2; r2 = 0.857; P < 0.001). Erythromycin cotreatment resulted loss two clearances (r2 = 0.39; P = 0.1). caused reduction original value 3.8 2.5 (95% CI difference −2.27, −0.35) ml kg−1 min−1. Interestingly there no change (6.4 vs 5.8 −2.74, −1.51) ml kg−1 min−1). Furthermore at all or clearances. Considering data day 3 intra-individual coefficient variation 45.3% 15 min 23.5% 30 min, respectively. Conclusions  It is concluded that but lost after inhibition by erythromycin. assessing intra- inter-individual variability clearance.