Comparative disposition of tripelennamine in horses and camels after intravenous administration

The pharmacokinetics of tripelennamine (T) was compared in horses (n = 6) a nd camels (n = 5) following intravenous (i.v.) administration of a dose of 0.5 mg/kg body weight. Furthermore, the metabolism and urinary detection ti me was studied in camels. The data obtained (median and range in brackets) in camels and horses, respectively, were as follows: the terminal eliminati on half-lives were 2.39 (1.91-6.54) and 2.08 (1.31-5.65) h, total body clea rances were 0.97 (0.82-1.42) and 0.84 (0.64-1.17) L/h/kg. The volumes of di stribution at steady state were 2.87 (1.59-6.67) and 1.69 (1.18-3.50) L/kg, the volumes of the central compartment of the two compartment pharmacokine tic model were 1.75 (0.68-2.27) and 1.06 (0.91-2.20) L/kg. There was no sig nificant difference (Mann-Whitney) in any parameter between camels and hors es. The extent of protein binding (mean +/- SEM) 73.6 +/- 8.5 and 83.4 +/- 3.6% for horses and camels, respectively, was not significantly statistical ly different (t-test). Three metabolites of T were identified in urine samples of camels. The firs t one resulted from N-depyridination of T, with a molecular ion of m/z 178, and was exclusively eliminated in conjugate form. This metabolite was not detected after 6 h of T administration. The second metabolite, resulted fro m pyridine ring hydroxylation, had a molecular ion of m/z 271, and was also exclusively eliminated in conjugate form. This metabolite could be detecte d in urine sample for up to 12 h after T administration. The third metaboli te has a suspected molecular ion of m/z 285, was eliminated exclusively in conjugate form and could be detected for up to 24 h following T administrat ion, T itself could be detected for up to 27 h after i.v. administration, w ith about 90% of eliminated T being in the conjugated form.