Effect of Age and Cardiopulmonary Bypass on the Pharmacokinetics of Lorazepam

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Abstract
The pharamacokinetics of lorazepam [an antianxiety agent] after 0.03 mg/kg i.v. administration was investigated in 14 surgical patients (nasal surgery under local anesthesia) ranging in age from 25-86 yr (8 males and 6 females). No statistically significant changes in the kinetics of lorazepam associated with the aging process were found. In these premedicated patients a slow onset of the drug action of lorazepam was assessed both subjectively and objectively with no apparent relationship to the age. These findings are of potential clinical importance, because it is highly desirable to use drugs for which age-related alterations are of minimum degree. In 5 male patients undergoing surgery with cardiopulmonary bypass, lorazepam disappeared from the plasma after a single 4 mg i.v. injection, with an apparent comparable half-life (10.0 .+-. 3.2 min) to that of the above-mentioned surgical patients. The concentrations of both unconjugated and conjugated lorazepam dropped abruptly at the start of extracorporeal circulation followed by an increase in the postperfusion period. After this peak effect the mean apparent half-life of lorazepam was 15.1 .+-. 5.8 h, indicating no great change in its elimination in comparison with patients operated under local anesthesia (half-life 12.1 .+-. 3.7 h). Pharmacokinetically, lorazepam appears to be a useful agent in connection with cardiopulmonary bypass operation.

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