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Abstract

Pharmacokinetics of the chemoprophylactic and chemotherapeutic trypanocidal drug isometamidium chloride (Samorin) in cattle.

M C Eisler
Drug Metabolism and Disposition December 1996, 24 (12) 1355-1361;
M C Eisler
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Abstract

Pharmacokinetics of the prophylactic and therapeutic trypanocidal drug isometamidium chloride were examined comprehensively for the first time in cattle using a recently described, highly sensitive ELISA. Cattle were administered single intravenous (N = 4) or intramuscular (N = 5) doses of isometamidium at a rate of 1.0 mg x kg(-1) body weight. Concentration data were analyzed over at least 14 days (intravenous treatment) or 30 days (intramuscular treatment) using compartmental and noncompartmental methods. After intravenous administration, apparent volumes of the central compartment (mean = 0.695 liter x kg(-1); range = 0.59-0.95) were large, and volumes of distribution at steady-state (mean = 24.5 liter x kg(-1): range = 18.5-39.3) were particularly large. After intramuscular administration, there was considerable individual variability in Cmax (mean = 111 ng x ml(-1); range = 37-197) and other pharmacokinetic parameters. Absorption kinetics seemed to be multifunctional, with fast and slow components; the mean t(max) was only 36 min (range = 20-60), although the mean absorption time was 282 hr, and the mean terminal elimination phase half-life after intramuscular administration (286 hr; range = 215-463) was over twice that after intravenous administration (mean = 135 hr; range = 123-165). The overall absolute bioavailability of intramuscular-administered isometamidium was 65.7%. These findings were consistent with extensive tissue binding at the intramuscular injection site to form a primary depot responsible for most of the prolonged chemoprophylactic effect of isometamidium, and an additional role for significant secondary drug depots formed by tissue binding elsewhere, particularly after intravenous administration.

 

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Drug Metabolism and Disposition
Vol. 24, Issue 12
1 Dec 1996
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Abstract

Pharmacokinetics of the chemoprophylactic and chemotherapeutic trypanocidal drug isometamidium chloride (Samorin) in cattle.

M C Eisler
Drug Metabolism and Disposition December 1, 1996, 24 (12) 1355-1361;

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Abstract

Pharmacokinetics of the chemoprophylactic and chemotherapeutic trypanocidal drug isometamidium chloride (Samorin) in cattle.

M C Eisler
Drug Metabolism and Disposition December 1, 1996, 24 (12) 1355-1361;
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