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Triprolidine radioimmunoassay: disposition in animals and humans.

A hapten derivative of triprolidine, bearing an acrylic acid side chain ortho to the pyridine ring nitrogen atom, was synthesized and coupled to bovine serum albumin. Immunization of New Zealand White rabbits with the resulting drug-protein conjugate resulted in the production of antisera capable of binding a radioiodinated tyramine conjugate of the triprolidine hapten derivative at high antiserum dilutions (1:70,000-1:150,000). These antisera were used to develop a radioimmunoassay (RIA) for triprolidine in human plasma with a sensitivity limit of 0.1 ng/mL (0.01 ng of actual mass). The known hydroxymethyl and carboxyl metabolites of triprolidine cross-reacted weakly (less than 2 and less than 0.05%, respectively) with this antiserum. The RIA could be used for the direct analysis of triprolidine in human and rabbit plasma, but not for rat or dog plasma, presumably due to the presence of other interfering substances (possibly metabolites). The validity of the RIA procedure in human plasma was demonstrated by comparative analysis of a number of samples by quantitative TLC (r = 0.985, slope = 1.076). The assay was employed to describe the pharmacokinetics of triprolidine in the rabbit (t 1/2, beta = 1.7 h). The assay had adequate sensitivity to detect low circulating drug concentrations in humans after therapeutic oral doses and also substantiated previous disposition experiments with triprolidine in humans (t 1/2, beta = 2.27 h). TLC analysis demonstrated that the absolute oral bioavailability of triprolidine (1-mg/kg dose) in the dog was low (4%). A comparison of triprolidine pharmacokinetic parameters in dogs, rabbits, rats, and humans revealed considerable similarity in elimination characteristics in these species.[1]

References

  1. Triprolidine radioimmunoassay: disposition in animals and humans. Findlay, J.W., Butz, R.F., Coker, G.G., DeAngelis, R.L., Welch, R.M. Journal of pharmaceutical sciences. (1984) [Pubmed]
 
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