Capillary Microsampling of 25 µL Blood For The Determination of Toxicokinetic Parameters in Regulatory Studies in Animals

Abstract

Background: Capillary microsampling (CMS) is a new technique for simplified collection, handling and analysis of small, exact volumes of liquid matrices. CMS was compared with conventional large volume sampling, in toxicology studies in rat and dog. Results: Bioanalytical validation data were well within acceptance limits. Toxicokinetic (TK) parameters from microsampling were in agreement with data from conventional volume sampling. Clinical pathology parameters in rats measured 2 days after repeated microsampling were not affected when compared with rats not sampled. Conclusion: The fast collection and simple handling of small, exact volumes of liquid blood makes the CMS technique generic and flexible, as well as easily implemented and automated. Presented data support that TK measurements can be performed in main study rats, instead of dosing additional satellite animals only for TK sampling, giving both a higher scientific value and a substantial reduction of animal numbers in preclinical development.

Utility of capillary microsampling for rat pharmacokinetic studies: Comparison of tail-vein bleed to jugular vein cannula sampling

“…In terms of the method for sampling, recent literature has at least two examples where CMS blood sampling has been used successfully for rat PK (or TK) studies (Dillen et al, 2014;Jonsson et al, 2012a). In one of these reports, the authors compared standard whole blood sampling to blood CMS and found that the two methods gave comparable results (Dillen et al, 2014).…”

“…Recent examples of microsampling in rodent PK or toxicokinetic (TK) studies have been published by Jonsson et al (Jonsson et al, 2012a;Jonsson, Villar, Nilsson, Eriksson, & Konigsson, 2012b;Jonsson et al, 2013;Nilsson, Ahnoff, & Jonsson, 2013), Dillen et al (Dillen et al, 2014) and Korfmacher et al (Korfmacher et al, 2015). The advantage of microsampling for rat PK studies is that the smaller volume can allow one to take more samples from each rat, so that serial bleeding could still be done even in a multiday PK study.…”

Incorporation of capillary microsampling into whole body plethysmography and modified Irwin safety pharmacology studies in rats

“…Capillary microsampling was recently introduced as a new technique for the simplified collection, handling and analysis of small, exact volumes of liquid matrices (Jonsson et al, 2012a) from laboratory animals. Following a short period in a warming chamber and minimal handling, blood volumes as low as 25e32 ml are accurately collected (Jonsson et al, 2012a(Jonsson et al, , 2012b, and as such, the impact on the animal, both in terms of welfare and on volumedepletion effects on clinical pathology parameters are much improved (Powles-Glover et al, 2014).…”

Amide Hydrolysis of a Novel Chemical Series of Microsomal Prostaglandin E Synthase-1 Inhibitors Induces Kidney Toxicity in the Rat

“…The samples were analyzed for only the parent molecule in toxicity studies 1 and 3, but both the parent molecules and M1 metabolite were analyzed in toxicity study 2. In toxicity study 3, a microsampling technique was used to sample data for toxicokinetic analysis (Jonsson et al, 2012). The TK parameters C max and area under the curve for 24 hours (AUC 0-24 ) were calculated with Pharsight WinNonlin (Pharsight, St. Louis, MO).…”