Comparative disposition of tripelennamine in horses and camels after intravenous administration.
The pharmacokinetics of tripelennamine (T) was compared in horses (n = 6) and camels (n = 5) following intravenous (i.v.) administration of a dose of 0.5 mg/kg body weight. Furthermore, the metabolism and urinary detection time was studied in camels. The data obtained (median and range in brackets) in camels and horses, respectively, were as follows: the terminal elimination half-lives were 2.39 (1.91-6.54) and 2.08 (1.31-5.65) h, total body clearances were 0.97 (0.82-1.42) and 0.84 (0.64-1.17)L/h/kg. The volumes of distribution 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 pharmacokinetic model were 1.75 (0.68-2.27) and 1.06 (0.91-2.20) L/kg. There was no significant difference (Mann-Whitney) in any parameter between camels and horses. The extent of protein binding (mean +/- SEM) 73.6 + 8.5 and 83.4 +/- 3.6% for horses and camels, respectively, was not significantly statistically different (t-test). Three metabolites of T were identified in urine samples of camels. The first 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 from pyridine ring hydroxylation, had a molecular ion of m/z 271, and was also exclusively eliminated in conjugate form. This metabolite could be detected in urine sample for up to 12 h after T administration. The third metabolite 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 administration. T itself could be detected for up to 27 h after i.v. administration, with about 90% of eliminated T being in the conjugated form.
Wasfi
I A
IA
Camelracing Laboratory, Abu Dhabi, United Arab Emirates. iawasfi@emirates.net.ae
Abdel Hadi
A A
AA
Elghazali
M
M
Boni
N S
NS
Alkatheeri
N A
NA
Barezaig
I M
IM
Al Muharami
A M
AM
Hamid
A M
AM
D000818:Animals; D019540:Area Under Curve; D002162:Camelus; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006207:Half-Life; D006634:Histamine H1 Antagonists / Q000097:blood / Q000378:metabolism* / Q000493:pharmacokinetics* / Q000652:urine; D006736:Horses; D007275:Injections, Intravenous; D008297:Male; D008657:Metabolic Clearance Rate; D013045:Species Specificity; D014018:Tissue Distribution; D014309:Tripelennamine / Q000097:blood / Q000378:metabolism* / Q000493:pharmacokinetics* / Q000652:urine
D006634:Histamine H1 Antagonists; D014309:Tripelennamine