Alteration of pharmacokinetic parameters for pentobarbital by ischemic stroke and reversion to normal by dexamethasone treatment

Abstract

The values of the pharmacokinetic parameters for pentobarbital were determined in 18 cats, 12 of which were subjected to acute ischemic stroke by ligation of the left middle cerebral artery (LMCA). All 18 ats received 50 mg/kg sodium pentobarbital during operation. The following three experimental groups were formed: control (sham-operated); ischemic stroke plus administration of 4 mg/kg dexamethasone; and ischemic stroke without dexamethasone administration. Ischemic stroke significantly prolonged the plasma half-life of pentobarbital, but concurrent administration of dexamethasone prevented this effect. Ischemic stroke significantly reduced the plasma clearance of pentobarbital, but dexamethasone prevented this reduction. Ischemic stroke significantly increased the area under the plasma pentobarbital concentration-time curve, but dexamethasone prevented this increase. Ischemic stroke significantly reduced the volume of distribution, but dexamethasone did not prevent this reduction. The alterations of the value of these pharmacokinetic parameters for pentobarbital by ischemic stroke and reversion to normal by dexamethasone treatment are discussed in the light of certain known circulatory changes which occur secondary to ischemic stroke and dexamethasone treatment.