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.), intramu scular (i.m.) and subcutaneous (s.c.) routes. Elimination of sulphadiazine was not affected by the route of administration (median t(1/2) 4.4-5.0 h) w hile elimination of trimethoprim was strongly limited by slow absorption fr om the injection site after s.c. and i.m. administration (median for appare nt t(1/2). 21-25 h) compared to that after i.v. administration (median t(1/ 2). 1.2 h; p<0.05) The median bioavailability of trimethoprim was also decr eased, being 37% and 55% after s.c. and i.m. administration, respectively W hen i.v. administration was used, trimethoprim concentration exceeded 0.1 m g/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 s ulphadiazine in milk behaved similar to that after i.v. administration, whi le trimethoprim time-concentration curves were flat and trimethoprim concen trations were around 0.1 mg/l for an extended period of time (8-12 h). Medi an C-max 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.