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Population pharmacokinetic and pharmacodynamic models were developed for DCA using NONMEM\u00ae software. The pharmacokinetic data were fit to a physiologic two\u2010compartment model, and the pharmacodynamic data were fit to an indirect physiologic response model. Simulations were employed to evaluate various dosing strategies for consideration in a pivotal Phase III clinical trial of DCA. For the pharmacokinetic model, it was discovered that the clearance of DCA decreased on multiple dosing from 4.82 L\/h to 1.07 L\/h and that the pharmacokinetics and pharmacodynamics in TBI patients could not be predicted from normal volunteers. Population pharmacokinetic modeling and simulation of the expected effects of several dosing strategies were useful procedures for designing a Phase III trial.<\/jats:p>","DOI":"10.1177\/00912700122010078","type":"journal-article","created":{"date-parts":[[2003,7,19]],"date-time":"2003-07-19T09:38:13Z","timestamp":1058607493000},"page":"259-267","source":"Crossref","is-referenced-by-count":9,"title":["Dichloroacetate: Population Pharmacokinetics with a Pharmacodynamic Sequential Link Model"],"prefix":"10.1002","volume":"41","author":[{"given":"Paul J.","family":"Williams","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James R.","family":"Lane","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Catherine C.","family":"Turkel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edmund 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