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.
Shoaf
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Department of Pharmacology, New York State College of Veterinary Medicine, Cornell University, Ithaca 14853.
Schwark
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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