Regional pharmacokinetics. II. Experimental methods.
Regional pharmacokinetics is the study of the drug concentrations in specific regions of the body. It allows greater insight into the mechanisms of drug disposition than the study of systemic blood concentrations. Experimental methods in regional pharmacokinetics and their applications and limitations are reviewed. Post-mortem tissue biopsies give the drug concentrations in highly specific regions of the body, but require a large number of animals. Serial tissue biopsies yield the time-course of drug concentrations in individual animals, but have limited applications. Regional blood sampling in vivo requires catheterization of blood vessels and a measure of regional blood flow, but allows repeated measurements of the time-course of regional drug concentrations in an individual. In contrast, artificially perfused regions allow greater control of perfusate flow and composition, but are less representative of the in vivo situation. These factors can be retained in some animals by surgically transplanting organs to another location to increase access. Tissues slices and cell cultures can examine drug uptake in the absence of perfusion, and tissue homogenates can be used to study the in vitro rates of drug metabolism and tissue drug binding.
Upton
R N
RN
Department of Anaesthesia and Intensive Care, University of Adelaide, Australia.
Runciman
W B
WB
Mather
L E
LE
D001345:Autoradiography; D001706:Biopsy; D001800:Blood Specimen Collection; D002478:Cells, Cultured; D010478:Chemotherapy, Cancer, Regional Perfusion; D046508:Culture Techniques; D006801:Humans; D010599:Pharmacokinetics; D012039:Regional Blood Flow; D014018:Tissue Distribution; D014180:Transplantation