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

Knoppert, N.W., Nijmeijer, S.M., van Duin, C.T.M., Korstanje, C., van Gogh, H. and van Miert, A.S.J.P.A.M. Some pharmacokinetic data of aditoprim and trimethoprim in healthy and tick-borne fever infected dwarf goats. J. vet. Pharmacol. Therap.11, 135—144. 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 (w = 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 t½β± 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 < 0.05). Mean Vdp± SEM values (1/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 < 0.05) for AP. After i.v. injection, rumen fluid concentrations of AP were significantly (P < 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 (Xg/ml and 0.85 ± 0.17 (ig/ml, respectively. After oral administration of TMP, Cmax in plasma was 0.12 ± 0.01 (ig/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 μg/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.