Has bovine somatotropin (BST) an effect upon drug disposition? Comparative studies in goats and cattle with sulphadimidine and antipyrine after parenteral administration of BST,zeranol and proligestone

Daily subcutaneous BST injection in lactating cows, bulls and castrated male dwarf goats did not induce significant changes in the pharmacokinetic parameters of antipyrine (AP) and sulphadimidine (SDD). Similarly, no changes were obtained after injection of slow-release BST formulations in lactating cows and non-lactating female goats. In contrast to androgenic hormones, both zeranol and proligestone had no effect upon the disposition of AP and SDD, although both synthetic hormones did induce enhanced plasma somatotropin concentrations. In goats, metabolic effects induced by zeranol and BST included significant reductions in plasma urea values, whereas plasma creatinine levels were somewhat lower after daily BST administration.     

Some pharmacokinetic data of aditoprim and trimethoprim in healthy and tick-borne fever infected dwarf goats

Aditoprim (AP) is a new dihydrofolate reductase inhibitor, which is structurally related to trimethoprim (TMP). The pharmacokinetics of AP (10 mg/kg) and TMP (20 mg/kg) were assessed in healthy dwarf goats. Therapeutic efficacy against rickettsial infections was tested in tick-borne fever (TBF) infected goats. The animals were given TMP (n = 5) or AP (n = 5) by i.v. injection, and subsequently the drugs were administered orally (same groups, similar doses). Finally, both groups were infected with TBF and the i.v. experiment was repeated. Plasma concentration-time curves for both drugs followed first-order two-compartment decay. For TMP, mean t1/2 beta +/- SEM (h) was 0.84 +/- 0.06 (i.v. control) and 0.90 +/- 0.06 (i.v. infected), respectively, whereas for AP values of 8.00 +/- 0.31 (i.v. control) and 10.28 +/- 0.67 (i.v. infected) were obtained (P less than 0.05). Mean Vd beta +/- SEM values (l/kg) were 3.84 +/- 0.27 (i.v. control) and 4.07 +/- 0.85 (i.v. infected) for TMP (NS) and 7.02 +/- 0.63 vs 9.29 +/- 0.21 (P less than 0.05) for AP. After i.v. injection, rumen fluid concentrations of AP were significantly (P less than 0.05) higher and more persistent than those of TMP. For AP, the plasma and rumen fluid concentrations at 3 h were 1.20 +/- 0.06 micrograms/ml and 0.85 +/- 0.17 microgram/ml, respectively. After oral administration of TMP, Cmax in plasma was 0.12 +/- 0.01 microgram/ml and the maximum was reached after 1.2 +/- 0.16 h; systemic bioavailability (F) was 10.3% (relative to AUC i.v.). Oral treatment with AP resulted in a Cmax value of 0.21 +/- 0.02 microgram/ml with Tmax of 22.5 +/- 1.65 h and a F value of 71%. Based on WBC, serum ALP and rectal temperature responses, it was concluded that both TMP and AP were inactive against Ehrlichia phagocytophila.     

The effect of testosterone and rutting on the metabolism and pharmacokinetics of sulphadimidine in goats

After testosterone pretreatment of castrated goats and during the rutting season of adult entire male goats, the oxidative metabolism of sulphadimidine (SDM) was inhibited markedly compared with the castrated control state of these animals. The oxidation of the 5 position (yielding 5-hydroxysulphadimidine) and of the 6-hydroxymethyl group (yielding 6-carboxysulphadimidine) was decreased equally, with that of the methyl group at the pyrimidine side chain itself being 6-hydroxymethylsulphadimidine (CH2OH), whereas the acetylation pathway was unaffected by testosterone. The consequence of altered metabolism by testosterone was a prolongation of SDM presence in the body. Effects on protein binding of the CH2OH metabolite and on the renal clearance of SDM were also investigated.     

Pharmacokinetics of nine sulphonamides in goats

Pharmacokinetics of nine sulphonamides was investigated in healthy goats. From the plasma disappearance curves after intravenous bolus injection clearance rates, plasma half-lives and distribution volumes were calculated. Plasma-protein binding was measured in vitro and in vivo. The highest-bound sulphonamides showed the highest concentration dependence of protein binding.
Plasma disappearance curves were in accordance with the one-, two- or three-compartment pharmacokinetic models. Disposition of sulphadimidine after 100 or 200 mg/kg and of sulphisomidine after 200 mg/kg showed limited enzyme capacity characteristics. Disposition of sulphadimidine, sulphisomidine and sulphadimethoxine was dose-dependent. Goats could also be divided in fast and slow sulphadimidine eliminators. Correlation was found only between clearance and half-life. Dosage regimens were calculated for seven sulphonamides.     

Pharmacokinetics of sulfadimethoxine and sulfamethoxazole in combination with trimethoprim after intravenous administration to healthy and pneumonic pigs

The pharmacokinetics of two sulfonamide/trimethoprim combinations were investigated after intravenous administration to clinically healthy pigs and to the same pigs following a challenge with Actinobacillus pleuropneumoniae toxins. Endobronchial challenge with A.pleuropneumoniae toxins resulted in fever, increased white blood cell counts and decreased water and feed consumption. Healthy, as well as febrile, pigs were given sulfadimethoxine (SDM) or sulfamethoxazole (SMX) intravenously at a dose of 25 mg/kg b.w. in combination with 5 mg trimethoprim (TMP) per kg body weight. The pharmacokinetic parameters of the sulfonamides as well as their main metabolites (acetyl sulfonamides) were not significantly different in healthy and febrile pigs. In healthy and pneumonic pigs, the mean elimination half-lives of SDM were 12.9 h and 13.4 h, respectively, those of SMX 2.5 h and 2.7 h, respectively, and those of TMP 2.8 h and 2.6 h, respectively. Distribution volumes in healthy and febrile pigs of SDM and SMX varied between 0.2 and 0.4 L/kg, and those of TMP between 1.1 and 1.6 L/kg. The mean AUC of TMP was decreased and the volume of distribution and total body clearance of TMP were increased in febrile pigs. Protein binding of the drugs and metabolites studied were not significantly changed after toxin-induced fever. The extent of protein binding of SDM, SMX and TMP was in the range 94–99%, 45–56% and 40–50%, respectively. Based on knowledge of in vitro antimicrobial activity of the drug combinations against A.pleuropneumoniae it was concluded that after intravenous administration of the dose administered (30 mg/kg of the combination preparations) to healthy and pneumonic pigs, plasma concentrations of SMX and TMP were above the concentration required for growth inhibition of 50% of A., pleuropneumoniae strains for approximately 16 h, whereas bacteriostatic plasma concentrations of SDM were still present after TMP had been eliminated from plasma. Because of similar elimination half-lives of SMX and TMP in pigs this combination is preferred to the combination of SDM with TMP.