Volume of distribution of C14-labeled tris(hydroxymethyl)aminomethane

Abstract

Seven cats and three dogs, after ligature of the renal vessels, were given 27.3–13.7 µc/kg body wt. of C¹⁴-labeled 2-amino-2-hydroxymethyl-1, 3-propanediol or tris(hydroxymethyl)aminomethane (THAM). One milliliter per kilogram of 10% inulin was simultaneously administered. Arterial pH was maintained close to 7.40. At this pH, 30% of THAM (pK 7.82 at 37 C) is un-ionized. Samples of plasma were withdrawn at 15, 30, and 60 min and 2, 3, 4, 5, and 6 hr. Plasma inulin concentration reached a plateau within 1–2 hr and had distributed in 21% of body weight. No C¹⁴ was detected in the expired CO₂. After 15 min the volume of C¹⁴ space was significantly larger (P < 0.02 > 0.01) than the inulin space. Plasma radioactivity approached a plateau after 4 to 6 hr, at which time the C¹⁴ was distributed into a volume corresponding to 55 ± 9% of body weight. If THAM is distributed evenly throughout body water and is not significantly degraded, it tends to equilibrate within 6 hr with the intracellular compartment.