Effects of diminazene aceturate on flip-flop plasma pharmacokinetics of piroxicam in dogs

Abstract

ObjectivesPain, fever and inflammation associated with protozoan infections caused by Trypanosomes, Babesia, Entamoeba, Leishmania and Pneumocystis have necessitated the search for polypharmacy,that could be used for treatment of protozoan infections in dogs. MethodsRandomized cross-over controlled trial was adopted for kinetic study of piroxicam (3.5 mg/kg) and piroxicam (3.5 mg/kg) administered with diminazene aceturate (3.5 mg/kg) in Nigerian indigenous dogs. Ten dogs comprised 5 males and females, each of about 8 ± 2 months and weighed 10 ± 0.5 kg were administered piroxicam, after one month the dogs were administered piroxicam and diminazene aceturate at different thigh muscles. Single dose was administered to avoid toxicity. Blood samples were collected at 0, 0.08, 0.25, 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 10, 12, 24, 48, 72 and 96 h for plasma analysis of piroxicam. ResultsFindings have shown that piroxicam was significantly (p < 0.05) slowly absorbed (5.823 ± 1.46 h−1) and eliminated (0.935 ± 0.75 h−1) as compared to piroxicam/diminazene aceturate group (7.405 ± 1.75 h−1) and (0.137 ± 0.10 h−1), respectively. Concentration maximum (Cmax = 12.659 ± 0.85 µg/ml), peak time (Tmax = 13.675 ± 9.21 h), absorption half-life (T1/2α = 0.016 ± 0.04 h), elimination rate constant (β = 0.137 ± 0.10 h−1), area under curve zero to infinity (AUC0-∞ = 778.885 ± 66.99 mg/L/h), area under moment curve (AUMC = 9820.140 ± 5.33 mg/h2/L), fraction absorbed zero to 96 h (Fab0-96h = 7.505 ± 0.00%) were significantly lower in piroxicam/diminazene aceturate (p < 0.05) as compared to Cmax(18.560 ± 2.97 µg/ml), Tmax (45.000 ± 11.49 h), T1/2α(0.250 ± 0.08 h), β (0.935 ± 0.75 h−1), AUC0-∞ (814.472 ± 86.43 mg/L/h), AUMC (36274.840 ± 9010.44 mg/h2/L), and Fab0-96h (7.848 ± 0.00%) in the piroxicam treated group, respectively. The elimination half-life was significantly lower (p < 0.05) in piroxicam (33.634 ± 9.34 h) as compared with piroxicam/diminazene aceturate (34.850 ± 11.94 h) treated group. ConclusionHence piroxicam displays flip-flop phenomenon of absorption, and could be coadministered with diminazene aceturate at single or twice dose for treatment of trypanosomosis, amoebiasis, leishmaniasis, pneumocytis and babesiosis in dogs.