Pharmacokinetic Profile of High Doses of Aprotinin in Patients Undergoing Primary Elective Hysterectomy

Abstract

24 female patients aged less than 60 years (mean 42.3 years), and 23 female patients aged more than 60 years (mean 70.1 years) who were undergoing primary elective abdominal or vaginal hysterectomy took part in 2 randomised, unblinded, parallel group studies to investigate the pharmacokinetic profile of high doses of aprotinin during clinical administration. In each study, the first treatment group received a single intravenous infusion of aprotinin 1 million kallikrein inactivator units (KJU) [140mg] after the start of the operation (first incision) over 30 minutes, while the second treatment group received aprotinin 2 million KIU (280mg) in the same manner. Blood and urine samples for aprotinin assays were collected over a 36.5-hour period following the start of the infusion. The results of the study with patients aged less than 60 years have been reported earlier, while the results of the study in patients aged more than 60 years are presented here for the first time. In addition, a meta-analysis of the 2 studies was performed. The results of both studies suggest that aprotinin, infused intravenously over a period of 30 minutes, displays dose-proportional pharmacokinetic characteristics over the dose range studied. The plasma concentrations of aprotinin decrease biphasically. The total urinary excretion of unchanged drug is very low, but appears to increase with the infused dose. Intravenous aprotinin was well tolerated, and the 2 doses employed were similar with respect to associated intraoperative blood loss. The pharmacokinetics of aprotinin were similar in patients aged less than and over 60 years.