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Determination of Loading Dose

Darrell R. Abernethy, MD, PhD; David J. Greenblatt, MD

Arch Neurol. 1985;42(5):468-471.

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.

Author Affiliations
From the Division of Clinical Pharmacology, Departments of Psychiatry and Medicine, Tufts University School of Medicine and New England Medical Center Hospital, Boston. Dr Abernethy is now with Baylor College of Medicine, Houston.

Footnotes
Accepted for publication April 24, 1984.

Reprint requests to Division of Clinical Pharmacology, Box 1007, Tufts—New England Medical Center, 171 Harrison Ave, Boston, MA 02111 (Dr Greenblatt).

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