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Polymorphic drug oxidation: pharmacokinetic basis and comparison of experimental indices.
Author(s) -
Jackson PR,
Tucker GT,
Lennard MS,
Woods HF
Publication year - 1986
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/j.1365-2125.1986.tb02933.x
Subject(s) - metabolite , pharmacokinetics , population , pharmacology , biology , medicine , endocrinology , environmental health
The pharmacokinetic basis for using various experimental indices, (urinary drug: metabolite and metabolite:drug + metabolite ratios, urinary metabolite recovery and AUC values), for detecting polymorphic oxidative drug metabolism was examined. Pharmacokinetic determinants in addition to partial metabolic clearance down the polymorphic route were identified in each index. The ability of the various indices to discriminate bimodality in population data was assessed using a computer simulation. With the exception of the AUC data, bimodality was apparent to varying extents in all of the frequency distributions and, in general, logarithmic transformation allowed clearer visualisation of the two phenotypic groups. Simulated distributions were compared with those observed experimentally for metoprolol and its alpha‐hydroxy metabolite. Detailed pharmacokinetic data from controlled studies in small numbers of volunteers can form the basis of the input to the simulation programme. Inspection of the output may help in the design of further studies in larger numbers of subjects in whom only limited data collection is possible.