Pharmacokinetic Modeling of Optimized Midazolam and Pentobarbital Dosing Used in Treatment Protocols of Refractory Status Epilepticus.

Objectives: To model bolus dosing, infusion rate, and weaning rate on theoretical serum concentration of midazolam and pentobarbital used in the treatment of refractory status epilepticus (RSE).
Design: One- and two-compartment in silico pharmacokinetic models of midazolam and pentobarbital.
Setting: Not applicable.
Subjects: Not applicable.
Interventions: We compared the model variables used in midazolam and pentobarbital protocols for standard RSE.
Measurements and Main Results: Standard RSE treatment protocols result in steady-state serum concentrations that are 6.2-9.0-fold higher for the one-compartment model and 2.3-4.7-fold higher for the two-compartment model. In the model, not including bolus doses delays the achievement of serum steady-state concentration by 0.5 and 2.7 hours for midazolam and pentobarbital, respectively. Abrupt discontinuation of these medications reduces modeled medication exposure by 1.1 and 6.4 hours, respectively.
Conclusions: Our in silico pharmacokinetic modeling of standard midazolam and pentobarbital dosing protocols for RSE suggests potential variables to optimize in future clinical studies.
Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest.
(Copyright © 2022 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)