Neurophysiological investigation of the central nervous action of the hypnotic agent etomidate in cats (author's transl)]

1. The action of etomidate (0.125-4.0 mg/kg) injected intravenously or into the right atrium (time of injection about 1 sec) was investigated in cats under different central nervous conditions. 2. In decerebrate unanaesthetized animals and in lightly anaesthetized (pentobarbitone) animals with an intact CNS etomidate (0.25-4 mg/kg i.v.) caused a decrease of the spontaneous lumbar fusimotor activity and a strong depression of the fusimotor pinnareflex. Partly a reversal of this reflex from excitation to inhibition was observed. The effects occurred within 20 sec after the injection and lasted for 5-70 min, showing a clear non-linear relationship with the injected dose. 3. In encephale isole preparations etomidate (0.125-1 mg/kg injected intra-right atrially) caused distinct changes of the spontaneous EEB (decrease of frequency, increase of amplitude, occurrence of steeper waves) and a depression of the arousal reactions in the EEB following different stimuli (acoustic stimuli and different stimuli in the area of the face and eyes). These effects occurred within 8 sec after the injection and lasted up to 40 min, dependent upon the injected dose. 4. The character and the principal similarity of the results observed in decerebrate animals and in animals with intact CNS suggest that a considerable part of the action of etomidate consists of a depression of the activity and reactivity of the brain stem reticular formation.     

Effect of hepatic dysfunction on oral cyclosporin pharmacokinetics in marrow transplant patients

The effect of hepatic dysfunction, defined as abnormal serum bilirubin level, on oral cyclosporin (CSP) pharmacokinetics was examined in 28 marrow transplant patients who received CSP for prophylaxis of graft-v- host disease. Serum CSP concentrations were measured by radioimmunoassay. Forty-one concentration-time courses were studied, divided among patients with no (less than 1.2 mg/dL), mild (1.2 to 2.0 mg/dL), and moderate (2.0 to 5.0 mg/dL) hepatic dysfunction. CSP elimination, as determined by elimination rate constant and clearance, was delayed in patients with moderate hepatic dysfunction compared to those with no hepatic dysfunction (P less than .05). The volume of distribution, lag time for absorption, maximum serum concentration, and time at which the maximum concentration was achieved was not affected by hepatic function. These data indicate that patients with moderate hepatic dysfunction have delayed CSP or CSP metabolite elimination and may be at higher risk for developing CSP-related toxicity.