Pharmacokinetics of sulfadimethoxine and ormetoprim in a 5:1 ratio following intraperitoneal and oral administration, in the hybrid striped bass (Morone chrysops x Morone saxitalis).
Selected pharmacokinetic parameters for sulfadimethoxine and ormetoprim, administered in a 5:1 ratio, via the oral and intraperitoneal (i.p.) routes were determined in the hybrid striped bass (Morone chrysops x Morone saxitalis). Plasma concentrations of both drugs were determined by high-performance liquid chromatography. A first-order one-compartment model adequately described plasma drug disposition. The elimination half-lives for sulfadimethoxine following i.p. and oral administration were 26 and 10.5 h, respectively. The half-lives for ormetoprim administered via i.p. and oral routes were 7.5 and 3.9 h, respectively. Cmax for sulfadimethoxine via the i.p. and oral routes were calculated to be 27.7 (+/-9.0) microg/mL at 3.6 h and 3.2 (+/-1.2) microg/mL at 1.2 h, respectively. Cmax for ormetoprim via the i.p. route was calculated to be 1.2 (+/-0.5) microg/mL at 9.1 h and 1.58 (+/-0.7) microg/mL at 5.7 h for the oral route. The oral availability of sulfadimethoxine relative to the i.p. route was 4.6%, while the oral availability of ormetoprim relative to the i.p. route was 78.5%. Due to the nonconstant ratio of these drugs in the plasma of the animal, the actual drug ratio to use for determining minimum inhibitory concentration (MIC) is unclear. Using the ratio of the total amount of each drug that is absorbed as a surrogate for the mean actual ratio may be the best alternative to current methods. Using this ratio as determined in these studies, (2.14:1 sulfadimethoxine:ormetoprim) to determine the MICs the single 50 mg/kg oral dose of the 5:1 combination of sulfadimethoxine and ormetoprim appears to provide plasma concentrations high enough to inhibit the growth of Yersinia ruckeri, Edwardsiella tarda, and Escherichia coli.
Environmental Medicine Consortium and Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USA. robert_bakal@fws.gov
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Stoskopf
D000284:Administration, Oral; D000333:Aeromonas / Q000187:drug effects; D000818:Animals; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D019540:Area Under Curve; D001492:Bass / Q000378:metabolism*; D003433:Crosses, Genetic; D004359:Drug Therapy, Combination; D020594:Edwardsiella / Q000187:drug effects; D004926:Escherichia coli / Q000187:drug effects; D007274:Injections, Intraperitoneal / Q000662:veterinary; D008826:Microbial Sensitivity Tests; D011549:Pseudomonas / Q000187:drug effects; D011743:Pyrimidines / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D013412:Sulfadimethoxine / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D015007:Yersinia / Q000187:drug effects
D000890:Anti-Infective Agents; D011743:Pyrimidines; D013412:Sulfadimethoxine; C100125:ormetoprim