Phenytoin Disposition in Obesity: Determination of Loading Dose

Darrell R. Abernethy, David J. Greenblatt

Research output: Contribution to journalArticlepeer-review

Abstract

Fourteen obese subjects (mean body weight, 124 kg; percent of ideal body weight [IBW], 178%) and ten control subjects of normal body habitus (mean body weight, 67 kg; 92% IBW) received 300 mg of phenytoin sodium by tenminute intravenous infusion. Obese subjects compared with controls had prolonged phenytoin elimination half-life (19.9 v 12.0 hours). Total metabolic clearance of phenytoin was greater in obese than in control groups, although the difference was not significant (59 v 39 mL/ min). Phenytoin half-life, inversely proportional to clearance and directly proportional to volume of distribution (Vd), was prolonged in obesity mainly as a result of the increase in Vd in obese subjects (84 v 40 L). Phenytoin loading dose should be calculated on the basis of IBW plus the product of 1.33 times the excess weight over IBW. Very obese individuals will require large absolute loading doses of phenytoin to rapidly achieve therapeutic drug concentrations.

Original languageEnglish (US)
Pages (from-to)468-471
Number of pages4
JournalArchives of neurology
Volume42
Issue number5
DOIs
StatePublished - May 1985

ASJC Scopus subject areas

  • Arts and Humanities (miscellaneous)
  • Clinical Neurology

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