Development and application of a specific and sensitive radioimmunoassay for trihexyphenidyl to a pharmacokinetic study in humans.
A radioimmunoassay (RIA) for trihexyphenidyl was developed through the use of a bovine thyroglobulin conjugate of trihexyphenidyl hemisuccinate. Immunization of New Zealand white rabbits with this drug-protein conjugate yielded antisera, for which the antibody titer and specificity were evaluated. An antiserum that had the highest titer and minimal cross-reactivities to major metabolites of trihexyphenidyl, such as trihexyphenidyl N-oxide (2%), hydroxytrihexyphenidyl (1%), and the antipsychotic drugs fluphenazine (< 1%), flupenthixol (< 1%), chlorpromazine (< 1%), and haloperidol (< 1%), was selected for development of a RIA. The described RIA enables the quantitation of 7.8 pg of trihexyphenidyl in 200 microL of human plasma with a mean coefficient of variation of < 6% across the range of the standard curve. Assay specificity was further demonstrated by comparison of results obtained directly and after selective extraction of trihexyphenidyl from replicate samples. This RIA procedure was applied to the analysis of steady state plasma samples obtained from patients undergoing treatment with trihexyphenidyl (2-8 mg) and plasma samples obtained from eight healthy male volunteers after administration of a single 4 mg oral dose of the drug. The results of the latter single dose studies demonstrated that the mean +/- SD for the peak concentration (Cmax), the time to Cmax (Tmax), the rate of absorption (Ka), and the area under the curve from 0 to 72 h (AUC0-72) were found to be 7.15 +/- 2.58 ng/mL, 1.32 +/- 0.58 h, 2.07 +/- 0.93 1/h, and 201 +/- 71 ng h/mL, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
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College of Pharmacy and Nutrition, University of Saskatchewan, Canada.
McKay
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Wirshing
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Midha
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D000818:Animals; D002746:Chlorpromazine; D003429:Cross Reactions; D005476:Fluphenazine; D006801:Humans; D007106:Immune Sera / Q000276:immunology; D008297:Male; D011817:Rabbits; D011863:Radioimmunoassay / Q000379:methods*; D051381:Rats; D013997:Time Factors; D014282:Trihexyphenidyl / Q000097:blood / Q000493:pharmacokinetics*
D007106:Immune Sera; D014282:Trihexyphenidyl; D005476:Fluphenazine; D002746:Chlorpromazine