A comparative pharmacokinetic study of intravenous and intramuscular midazolam in patients with epilepsy

The pharmacokinetics of midazolam, a water soluble 1,4-benzodiazepine, has been studied in 12 patients (11 male, 1 female; age range 19-57 years) with epilepsy. All patients were taking hepatic enzyme inducing antiepileptic drugs (AEDs) on a regular basis. Midazolam (5 mg) was administered intravenously and 1 week later midazolam was administered intramuscularly, the dose used being dependent on the sedative response to the intravenous dose (10 mg, n = 2; 7 mg, n = 8; 5 mg, n = 2). Serial blood samples were collected at timed intervals for 5-7 h. After intravenous administration initial distribution was rapid with a mean half-life (t 1/2 /α) of 0.06 ± 0.03 h followed by a terminal half-life (t 1/2 β or γ) of 1.5 ± 0.3 h. Volume of distribution was 0.62 ± 0.27 l/kg. After intramuscular administration midazolam was rapidly absorbed with peak serum concentrations achieved at 25 ± 23 min. Two patients showed delayed absorption. Mean terminal half-life was 2.8 ± 1.7 h. The absolute bioavailability of intramuscular midazolam was calculated in 11 patients as 87 ± 18%.