Arterial-Venous Concentration Gradient as a Potential Source of Error in Pharmacokinetic Studies. Plasma Concentration Differences of 6-Chloro-2-Pyridylmethyl Nitrate on Constant Infusion to Rats

Abstract

1. Plasma concentrations of 6-chloro-2-pyridylmethyl nitrate (CPMN) at different sampling sites in the circulation were determined during and after constant infusion in the rat.

2. An arterial-venous CPMN concentration gradient was found and characterized by the following trends. During CPMN infusion into the right atrium, plasma concentrations were higher in arterial (aortic arch) than venous (inferior vena cava) plasma. After cessation of infusion the venous plasma concentrations were significantly higher (P<0-05) than those in arterial samples. There was a low concentration gradient between the right atrium and the peripheral artery, but substantial difference between the peripheral artery and the vein. There was a 1.8–2.4 extraction ratio of CPMN across the arterial-venous bed.