Ormetoprim-sulfadimethoxine in cattle: pharmacokinetics, bioavailability, distribution to the tears, and in vitro activity against Moraxella bovis.
The pharmacokinetics, bioavailability, and distribution to the tears of ormetoprim (OMP; 5.5 mg/kg of body weight) and sulfadimethoxine (SDM; 27.5 mg/kg of body weight) were determined following IV or oral administration to 6 Holstein steers. After IV administration, the disposition kinetics of both drugs were best described by a 2-compartment open model. Sulfadimethoxine had a moderately rapid distribution phase, followed by a slower elimination phase, with a mean half-life (t 1/2) of 7.91 hours. The mean volume of distribution of SDM was 185 ml/kg, and the mean body clearance was 0.28 ml/min X kg. The concentration of SDM in tears was lower than the corresponding plasma concentration, and the elimination of SDM from tears (t 1/2 = 3.02 hours) was significantly faster than its elimination from plasma (t 1/2 = 7.91 hours). The disposition of OMP administered IV was characterized by a rapid distribution phase, followed by a rapid elimination phase (t 1/2 = 1.37 hours). The high values of the mean volume of distribution (1,450 ml/kg) and mean rate of body clearance (13.71 ml/min X kg) indicated that OMP was widely distributed in the body and was rapidly cleared from the body. Ormetoprim concentrations in tears exceeded corresponding plasma concentrations, and the elimination of OMP from tears was significantly slower (t 1/2 = 1.91 hours) than from plasma (t 1/2 = 1.37 hours). After oral administration of an OMP-SDM combination in bolus form, the absorption of SDM was slow (absorption t 1/2 = 3.32 hours), but complete.(ABSTRACT TRUNCATED AT 250 WORDS)
D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D002417:Cattle / Q000378:metabolism*; D004338:Drug Combinations; D007262:Infusions, Intravenous; D007700:Kinetics; D008297:Male; D009016:Moraxella / Q000187:drug effects*; D011743:Pyrimidines / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology; D012044:Regression Analysis; D013412:Sulfadimethoxine / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology; D013666:Tears / Q000378:metabolism*
D004338:Drug Combinations; D011743:Pyrimidines; D013412:Sulfadimethoxine; C100125:ormetoprim