NEW INTRAVENOUS DRUG ADMINISTRATION AND BLOOD SAMPLING MODEL IN THE AWAKE RAT

摘要

There is a continuing need for increased throughput in the examination of newchemical entities (NCEs) in terms of the pharmacokinetic (PK) parameters. Theaim was to validate a new study method which allows a higher throughput, theexamination of inter-animal variability and a reduction in the numbers ofanimals needed for routine bioavailability studies of NCEs in awake rats. Thedesign uses a new method for intravenous (iv) administration via the saphenousvein in combination with serial blood sampling via the tail vein. The multiplesampling method was compared with single sampling (decapitation) and theeffect on haematocrit (Hct) levels was studied. Direct injection in thesaphenous vein was compared to iv administration using an indwelling jugularcatheter. Using structural different CE's, it was shown that a combination ofdirect injection via the saphenous vein and multiple sampling from the tailvein produces comparable plasma concentrations and subsequent PK results tothe comparator methods. Furthermore, Hct levels remained within recommendedlevels using a total blood sampling volume of up to 2.1 ml per day. The newtechnique increases throughput by reducing the time required for preparativesurgery, increases the quality by allowing inter-animal comparison of major PKparameters as concentration time curves can be collected from each animal andreduces the number of animals required.