The effect of age and diet on sulfadiazine/trimethoprim disposition following oral and subcutaneous administration to calves.
Thirty milligrams per kilogram of sulfadiazine/trimethoprim (SDZ/TMP, Tribrissen) was given orally and subcutaneously (s.c.) to two groups of male, Holstein calves. One group was fed milk-replacer throughout the 13-week period of the study while the second group was weaned onto a chopped grain-fiber mixture when 5 weeks old. Serum and urine were assayed for concentrations of unchanged drug. Trimethoprim bioavailability, following oral administration at 1, 6 and 12 weeks of age, is higher in milk-fed calves (non-ruminants) than in grain-fiber-fed calves (ruminants); bioavailability decreases with increasing age in both groups of calves. Serum concentrations above 0.1 micrograms/ml (the level of sensitivity of the assay) could not be obtained in ruminating calves. The rate of SDZ absorption following oral administration, as determined by the Wagner-Nelson method, was very slow in all the calves in this study with average half-life values ranging from 8.2-12.67 h; absorption was slightly faster in ruminating calves. Absorption of SDZ is rate-limiting and determines the biological half-life of the drug; SDZ serum concentrations above 2 micrograms/ml were maintained in all calves for at least 24 h. Following s.c. administration of Tribrissen to 7-and 13-week-old calves, urinary excretion patterns indicated that TMP was slowly released from the injection site; serum concentrations were below 0.1 micrograms/ml. In contrast, absorption of SDZ was very rapid; values for tmax were 1.5-1.8 h. The pharmacokinetic parameters for SDZ were calculated according to a one-compartment open model; neither diet nor age had a significant effect on SDZ disposition following s.c. injection. Subcutaneous administration of 30 mg/kg Tribrissen, b.i.d., may be the best therapeutic regimen; even though measureable concentrations of TMP cannot be achieved in the serum following a single s.c. dose, TMP concentrations should accumulate and, because of its sustained release, provide almost continual potentiation of SDZ.
Department of Pharmacology, New York State College of Veterinary Medicine, Cornell University, Ithaca 14853.
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D000042:Absorption; D000284:Administration, Oral; D000367:Age Factors; D000818:Animals; D001682:Biological Availability; D002417:Cattle / Q000378:metabolism*; D004032:Diet; D004338:Drug Combinations / Q000008:administration & dosage / Q000378:metabolism; D004357:Drug Synergism; D006207:Half-Life; D007279:Injections, Subcutaneous / Q000662:veterinary; D008297:Male; D013411:Sulfadiazine / Q000008:administration & dosage / Q000378:metabolism* / Q000493:pharmacokinetics*; D014295:Trimethoprim / Q000008:administration & dosage / Q000378:metabolism* / Q000493:pharmacokinetics*; D000096926:Benzenesulfonamides
D004338:Drug Combinations; D013411:Sulfadiazine; D014295:Trimethoprim; C024873:sulfadiazine, trimethoprim drug combination; D000096926:Benzenesulfonamides