Pharmacokinetics of sulphadiazine-trimethoprim in lactating dairy cows.
Five Finnish Ayrshire cows in mid or end-lactation were treated with 40 mg sulphadiazine/kg and 8 mg trimethoprim/kg using intravenous (i.v.), intramuscular (i.m.) and subcutaneous (s.c.) routes. Elimination of sulphadiazine was not affected by the route of administration (median t1/2 4.4-5.0 h) while elimination of trimethoprim was strongly limited by slow absorption from the injection site after s.c. and i.m. administration (median for apparent t1/2 21-25 h) compared to that after i.v. administration (median t1/2 1.2 h; p < 0.05). The median bioavailability of trimethoprim was also decreased, being 37% and 55% after s.c. and i.m. administration, respectively. When i.v. administration was used, trimethoprim concentration exceeded 0.1 mg/l in milk between 0.15-8 h while sulphadiazine concentrations above 2 mg/l were maintained from 0.5-2 h to 8 h. After s.c. and i.m. administration sulphadiazine in milk behaved similar to that after i.v. administration, while trimethoprim time-concentration curves were flat and trimethoprim concentrations were around 0.1 mg/l for an extended period of time (8-12 h). Median Cmax values in milk were only 0.07 mg/l and 0.10 mg/l for s.c. and i.m. administrations, respectively. After s.c. administration, 4 out of 5 cows showed signs of pain. After i.m. administration, 2 of the cows showed clear signs of pain and one had some local tenderness at the site of injection.
Kaartinen
L
L
University of Helsinki, Facility of Veterinary Medicine, Department of Clinical Sciences, Finland.
Löhönen
K
K
Wiese
B
B
Franklin
A
A
Pyörälä
S
S
D000818:Animals; D000892:Anti-Infective Agents, Urinary / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D002417:Cattle; D005260:Female; D006207:Half-Life; D007273:Injections, Intramuscular; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D008657:Metabolic Clearance Rate; D008892:Milk / Q000737:chemistry; D013411:Sulfadiazine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D014295:Trimethoprim / Q000008:administration & dosage / Q000493:pharmacokinetics*
D000892:Anti-Infective Agents, Urinary; D013411:Sulfadiazine; D014295:Trimethoprim