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.

Toxicological and pathological findings in fatalities involving pentazocine and tripelennamine.

Toxicological and pathological findings are described in fatalities involving pentazocine (Talwin) and tripelennamine (Pyribenzamine). Procedures using thin-layer chromatography, gas chromatography, ultraviolet spectrophotometry, and spectrophotofluorometry are described, as well as the quantitative analysis of biological specimens of drug abuse and homicide victims. Microscopic findings in lung specimens from drug abuse deaths are also described.

Detection of pentazocine and tripelennamine in urine.

Pentazocine and tripelennamine can be identified in urine as a part of routine screening for drug abuse. Pentazocine, pentazocine hydrate, and tripelennamine can be detected by thin-layer chromatography of chloroform/isopropanol extracts of heat- and acid-hydrolyzed urine. Gas chromatography is used for confirmation. Gas chromatographic/mass spectrometric studies (chemical ionization mode) show that such extracts contain major molecular (M+) ions of m/e 256, 286, and 304, indicating the presence of tripelennamine, pentazocine, and pentazocine hydrate, respectively.

Metabolism of tripelennamine in man.

Four polar metabolites were isolated from the urine of human subjects orally treated with tripelennamine, and their structures elucidated by various chemical and physical methods. One of the metabolites, which is a minor one, was identified as an N-oxide of tripelennamine, and the other three as glucuronide conjugates. One of the conjugates, which is a major metabolite, has been assigned a unique quaternary ammonium N-glucuronide structure, since it gave tripelennamine and D-glucuronic acid on incubation with beta-glucuronidase. The N-oxide, which has also been prepared synthetically, remained unchanged on similar treatment. The other two conjugates were O-glucuronides of hydroxylated derivatives, the glucuronide of hydroxytripelennamine being the principal metabolite. No desmethyltripelennamine was found in the urine, however. Hydroxylation in both cases had occurred in the pyridine ring.