Abstract
ABSTRACT
Introduction
Post‐anoxic status epilepticus (PASE) is a frequent neurologic complication following hypoxic–ischemic brain injury in cardiac arrest survivors, for which no definitive treatment exists. Early γ‐Aminobutyric Acid (GABA) augmentation using vigabatrin, a GABA‐transaminase inhibitor, has been proposed; however, its pharmacokinetics (PK) in this critically ill population are unknown. In this ancillary study of VIGAB‐STAT, an open‐label feasibility trial of loading dose vigabatrin via enteral tube, we evaluated vigabatrin PK.
Materials and Methods
Comatose adults with electrographic status epilepticus following return of spontaneous circulation received a loading dose of vigabatrin determined by renal function (creatinine clearance (CrCl) ≥ 50 mL/min, 4500 mg; CrCl 30–50 mL/min, 2250 mg; CrCl
Results
Six participants contributed 56 plasma samples. The median (range) age was 62 years (22–68), weight 80.9 kg (57.6–139.9), and four (66.7%) participants were male. Loading doses were evenly distributed: 4500 mg (
n
= 2), 2250 mg (
n
= 2), and 1125 mg (
n
= 2). Time to maximum concentration, maximum concentration, area under the concentration time curve from 0 to 24 h, area under the concentration time curve from 0 to infinity and half‐life median (range) values were 2 h (1–3), 38.1 mg/L (16.9–91.8), 431.2 mg*h/L (254.6–979.3), 679.3 mg*h/L (340.3–1156.8), and 16.2 h (9.4–23.9), respectively.
Conclusions
This pioneer vigabatrin PK study in critically ill participants with PASE demonstrated absorption regardless of challenges such as enteral delivery type, co‐administration of gastric pH modulators, vasopressors, and anesthetics. Notably, prolonged elimination half‐lives and increased exposures were observed.