In the present study the feed and water consumption and pharmacokinetic parameters of orally administered oxytetracycline were compared in clinically healthy pigs and in the same pigs following a challenge with Actinobacillus (Haemophilus) pleuropneumoniae toxins. Endobronchial challenge with A. pleuropneumniae toxins was accompanied by anorexia, increased lassitude, labored breathing, fever, and increased white blood cell counts. Pleuropneumonia was evident in all pigs on autopsy. Following the challenge, both feed and water consumption were markedly reduced. In contrast to recommendations in the literature, it is concluded that drugs should not be administered to pneumonic pigs via water. In healthy pigs the oral bioavailability of oxytetracycline (50 mg/kg), given on an empty stomach, was 4.8% and the elimination half-life (t1/2 beta) was 5.92 h. After challenge, the pigs showed great variation in oxytetracycline plasma concentrations. In addition, the mean computed elimination rate constant (beta), t1/2 beta, the area under the plasma concentration-time curve (AUC), and clearance in pneumonic pigs differed significantly (P less than .05) from the values found in healthy pigs. The elimination half-life (t1/2 beta), AUC, and volume of distribution (Vd area) were increased. In diseased pigs the mean of maximum plasma concentrations (.87 micrograms/ml) was reached after 7 h, in contrast to 1.74 h (1.87 micrograms/ml) in the healthy pigs.

Based on a review of the literature, a comparison is made of the pharmacokinetics of penicillins, aminoglycosides, and chloramphenicol in birds and mammals. Penicillins in birds are likely to be more dependent for their elimination on biotransformation than in mammals. Amoxycillin had a relatively low availability (0.34) after p.o. administration. Higher doses (2 to 8 times) were needed to achieve the same peak levels in birds and mammals. Aminoglycosides, which for their elimination largely depend on renal excretion by glomerular filtration, show only minor differences in pharmacokinetics between birds and mammals. Chloramphenicol is mainly excreted after biotransformation and large differences in pharmacokinetic parameters are to be found, not only between birds and mammals, but also between avian species.

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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.