Abstract
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 t½4.4–5.0 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 t½. 21–25 h) compared to that after i.v. administration (median t½ 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.
Keywords: bovine, antimicrobial substances, potentiated sulphonamides, trimethoprim, intramuscular, subcutaneous, intravenous, milk
Sammanfattning
Fem finska Ayrshirekor i mitt- eller slutfasen av mjölkproduktionsperioden behandlades intravenöst, intramuskulärt och subkutant med 40 mg sulfadiazin och 8 mg trimetoprim per kg kroppsvikt. Administreringssättet påverkade inte elimineringen av sulfadiazin (median t½ 4.3–5.0 h). Halveringstiden för trimetoprim var på grund av dålig absorption från injektionsstället efter subkutan och intramuskulär behandling mycket längre (median för skenbar t½ 21–25 h) än efter intravenös administration (t½ 1.2 h; p<0.05). Medianen for trimetoprimets biotillgänglighet var också lägre (37% och 55% efter subkutan respektive intramuskulär behandling). Trimetoprimkoncentrationen var högre än 0.1 mg/l i mjölk 0.15 h–8 h efter intravenös behandling, medan sulfadiazinkoncentrationen överskred 2 mg/l efter 0.5–2 h till 8 h. Sulfadiazins farmakokinetik var likartad oberoende av administrationssätt. Tid-koncentrationskurvan for trimetoprim i mjölk var flack efter intravenös behandling och cirka 0.1 mg/l uppmättes under en längre tidsperiod (8–12 h). Efter subkutan och intramuskulär behandling uppgick maximalkoncentrationernas medianvärden endast till 0.07 respektive 0.1 mg/l. Efter subkutan behandling visade 4 av 5 kor tecken på smärta. Efter intramuskulär behandling visade 2 av 5 behandlade kor tydliga smärtsymptom och hos en ko påvisades lindrig omhet på injektionsstället.
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