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Nonlinear ethotoin kinetics
Author(s) -
Meyer Marvin C,
Holcombe Beverly J,
Burckart Gilbert J,
Raghow Gursharan,
Yau Martin K
Publication year - 1983
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1983.41
Subject(s) - dosing , kinetics , pharmacokinetics , plasma concentration , nonlinear model , chemistry , medicine , pharmacology , chromatography , nonlinear system , physics , quantum mechanics
Five healthy subjects were given single 500‐, 1500‐, and 2500‐mg doses of ethotoin as 250‐mg tablets at 7‐day intervals. Plasma samples were collected for 49 hr after dosing and were assayed by HPLC for ethotoin. The drug was more slowly absorbed after the two higher doses. There was a disproportionate increase in AUC in all subjects with the escalating doses. Individual subject data were fitted to a first‐order model and one incorporating Michaelis‐Menten elimination kinetics. Eleven of the 15 data sets were best described by the nonlinear model. All subjects reported visual disturbances with the two higher doses, and four of five experienced dyscoordination of gait with the 2500‐mg dose. These effects did not appear to be related to plasma ethotoin concentration. Clinical Pharmacology and Therapeutics (1983) 33, 329–334; doi: 10.1038/clpt.1983.41