COMPARATIVE ABSORPTION KINETICS OF INTRAMUSCULAR MIDAZOLAM AND DIAZEPAM

Purpose: This study investigates the rare and extent of absorption fol lowing intramuscular injection of midazolam and diazepam. Methods: Fou r healthy male volunteers were recruited in this randomized three-way cross-over study. On one occasion each subject received simultaneous i m injections of 5 ms midazolam and 10 ms diazepam in separate deltoid muscles. On two other separate occasions each subject received an iv i nfusion of 7.5 ms midazolam and 30 ms diazepam over five minutes. Freq uent arterial blood samples were collected for Icp to two hours and ve nous blood samples were collected for up to 24 hours for midazolam and ten days for diazepam. A gas chromatography assay was used to determi ne the plasma concentrations of midazolam and diazepam. The im absorpt ion profiles were estimated using constrained least-squares deconvolut ion. Results: There were substantial intersubject variabilities in the estimated pharmacokinetic parameters (volumes and clearances) of intr avenous midazolam and diazepam The mean (+/-sd) time to peak plasma co ncentration ((max)) was shorter for im midazolam (17.5 +/- 6.5 min) re lative to diazepam (33.8 +/- 7.5 min). The mean (+sd) time to peak abs orption rate was also shorter for midazolam (9 +/- 2 vs 13.8 +/- 7.5 m in). The peak rate of absorption was identical (0.18 ms min(-1)) and b ioavailability was 1.0 for both drugs. Conclusions: We conclude that m idazolam has more rapid absorption than diazepam following in administ ration.