Effect of Diminazine Accturate on the Pharmacokinetic of a Long Acting Oxytetracycline Formulation in Lactating Goats

Youssef, S; Amer, A; Galal, A; Constable, P

doi:10.21608/vmjg.2010.368179

Effect of Diminazine Accturate on the Pharmacokinetic of a Long Acting Oxytetracycline Formulation in Lactating Goats

Document Type : Original Article

Authors

¹ Pharmacology Department Faculty of Veterinary Medicine, Cairo University

² Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Purdue University, West Lafayette, Indiana, USA.

10.21608/vmjg.2010.368179

Abstract

Oxytetracycline (OTC) and diminazene aceturate are commonly administered to diseased ruminants with mixed bacterial and the protozoal infections. We were therefore interested in characterizing pharmacokinetics of a new long acting OTC formulation after IV or IM administration, and whether concurrent administration of diminazene altered the pharmacokinetics. Ten clinically healthy lactating female Baladi goats were used in a sequential order. Goats received the treatments in sequential order with a 2 week wash out period between each study: 1) a single dose of OTC (30 mg/kg PW) by IV or IM injection in non-treated and diminazine aceturate pre-treated goats (3.5 mg/kg BW) 2 hours before OTC treatment. Blood, milk and urine samples were collected periodically and OTC concentration was assayed using microbiological method. The extent of protein binding in serum and milk was determined using an in vitro ultrafiltration method and assayed using the same method as serum Pharmacokinetic analysis indicated that serum OTC concentrations after IV administration could be fit to a two-compartment model, and that pre-treatment with diminazene aceturate increased serum OTC concentrations. Following IV injection (t_0.5β) was 25.9 ± 5.1 and 24.5 ± 2.7 hours, and (Vd_area) Was 22.0 ± 0.8 and 23.7 + 0.4 L.kg^-1, in non-treated and diminazine pre-treated goats, respectively. The maximum OTC concentration after IM injection (1.25 + 0.02µg ml^-1and 1.39 ± 0.04 µ g.ml^-1) was obtained at 1.8 ± 0.3 hours and 2.4±0.4 hours in non-treated and diminazine pre-treated goats, respectively. Moreover, effective milk concentrations were detected for 24 to 48h, and effective urine concentrations were detected for 96 to 120 h after IM injection. The LA-OTC formulation was moderately bound goat serum protein (46.0 ± 3.2 % for OTC alone and 40.0 ± 2.3 % for OTC + diminazine). The binding of the LA-OTC formulation was lower in milk (29.3 ± 3.6 %) than plasma. We conclude that concurrent administration of LA-OTC and diminazine aceturate alters the serum concentration-time profile and pharmacokinetics of a new long acting OTC formulation and could therefore potentially alter treatment efficacy.

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