Oral absorption profiles of sulfonamides in Shiba goats: a comparison among sulfadimidine, sulfadiazine and sulfanilamide

The oral pharmacokinetics of three sulfonamides, sulfadimidine (pKa 7.5), sulfadiazine (pKa 6.5) and sulfanilamide (pKa 10.5), with different rates of unionization in rumen juice, were compared in Shiba goats to clarify the relationship between drug absorption profiles after their oral administration as well as their degree of unionization in the rumen. Sulfonamides were administered either into the left jugular vein or orally to five male goats at doses of 10 mg/kg body weight, using a crossover design with at least a 3-week washout period. The Tmax of sulfadimidine, sulfadiazine and sulfanilamide reached 2.0 ± 1.2, 6.0 ± 0.0, and 7.8 ± 1.6 hr, respectively, after their oral administration, and this was followed by their slow elimination due to a slow rate of drug absorption from the gastrointestinal tract. The MAT and t1/2ka of sulfadiazine (13.2 ± 2.0 and 10.9 ± 1.08 hr) were significantly longer than those of sulfanilamide (9.09 ± 1.67 and 7.46 ± 1.70 hr) and sulfadimidine (7.52 ± 0.85 and 5.17 ± 0.66 hr). These results suggest that the absorption rates of highly unionized drugs (such as sulfanilamide and sulfadimidine) from the forestomach of goats may be markedly higher than less unionized ones (such as sulfadiazine). The mean oral bioavailability of sulfadiazine was high (83.9 ± 17.0%), whereas those of sulfadimidine and sulfanilamide were low (44.9 ± 16.4% and 49.2 ± 2.11%, respectively).