Semiparametric models for antagonistic drug interactions.
A new class of models to describe antagonistic drug interactions are presented. They are semiparametric in that they use nonparametric functions (splines) but are forced to obey certain constraints corresponding to reasonable assumptions. We propose the models primarily for exploratory data analysis, but they may also be definitive models for such purposes as predicting future responses. Certain problems that arise in semiparametric modeling, such as model selection, are addressed so that we can propose a relatively automatic and objective approach to model determination. We demonstrate the applicability of the class of models we propose to two real data set examples involving pain relief response to opioid agonists/antagonists. The results suggest that the semiparametric approach is particularly useful when unusual shapes link dose to response.
Troconiz
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Department of Pharmacy, School of Pharmacy, University of California, San Francisco 94143.
Sheiner
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Verotta
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D000818:Animals; D001667:Binding, Competitive; D004336:Drug Antagonism; D004347:Drug Interactions; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004745:Enkephalins / Q000494:pharmacology; D007276:Injections, Intraventricular; D008954:Models, Biological; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D051381:Rats; D017465:Receptors, Opioid, delta / Q000037:antagonists & inhibitors; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors / Q000187:drug effects; D013004:Somatostatin / Q000031:analogs & derivatives / Q000494:pharmacology
D004745:Enkephalins; D009292:Narcotic Antagonists; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; C049352:phenylalanyl-cyclo(cysteinyltyrosyl-tryptophyl-ornithyl-threonyl-penicillamine)threoninamide; D013004:Somatostatin; D009271:Naltrexone; C055382:naltrindole