PHARMACOKINETICS OF THE CHEMOPROPHYLACTIC AND CHEMOTHERAPEUTIC TRYPANOCIDAL DRUG ISOMETAMIDIUM CHLORIDE (SAMORIN) IN CATTLE

Pharmacokinetics of the prophylactic and therapeutic trypanocidal drug isometamidium chloride were examined comprehensively for the first ti me in cattle using a recently described, highly sensitive ELISA, Cattl e were administered single intravenous (N = 4) or intramuscular (N = 5 ) doses of isometamidium at a rate of 1.0 mg . kg(-1) body weight, Con centration data were analyzed over at least 14 days (intravenous treat ment) or 30 days (intramuscular treatment) using compartmental and non compartmental methods. After intravenous administration, apparent volu mes of the central compartment (mean = 0.695 liter . kg(-1); range = 0 .59-0.95) were large, and volumes of distribution at steady-state (mea n = 24.5 liter . kg(-1): range = 18.5-39.3) were particularly large. A fter intramuscular administration, there was considerable individual v ariability in C-max (mean = 111 ng . ml(-1); range = 37-197) and other pharmacokinetic parameters, Absorption kinetics seemed to be multifun ctional, with fast and stow components; the mean t(max) was only 36 mi n (range = 20-60), although the mean absorption time was 282 hr, and t he mean terminal elimination phase half-life after intramuscular admin istration (286 hr, range = 215-463) was over twice that after intraven ous administration (mean = 135 hr; range = 123-165), The overall absol ute bioavailability of intramuscular-administered isometamidium was 65 .7%, These findings were consistent with extensive tissue binding at t he intramuscular injection site to form a primary depot responsible fo r most of the prolonged chemoprophylactic effect of isometamidium, and an additional role for significant secondary drug depots formed by ti ssue binding elsewhere, particularly after intravenous administration.