Prolongation of midazolam half-life after sustained infusion for status epilepticus

Midazolam clearance was examined in two patients with medically refractory convulsive status epilepticus. One patient received a constant infusion of midazolam for 68 hours and the other patient received a constant infusion of midazolam for 148 hours. In both patients the decline in level was, overall, much slower than expected. The half-lives of the terminal phase were longer than typically published (52.9 hours in Patient 1 and 20.1 hours in Patient 2). Thus, the data suggest that midazolam exhibits use-dependent pharmacokinetic changes that may be important clinically in situations that require prolonged midazolam therapy.