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Trazodone kinetics: Effect of age, gender, and obesity
Author(s) -
Greenblatt David J,
Friedman H,
Burstein Ethan S,
Scavone Joseph M,
Blyden Gershwin T,
Ochs Hermann R,
Miller Lawrence G,
Harmatz Jerold S,
Shader Richard I
Publication year - 1987
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.1987.132
Subject(s) - trazodone , medicine , body weight , bioavailability , obesity , volume of distribution , endocrinology , oral administration , pharmacokinetics , antidepressant , hippocampus , pharmacology
Single 25 mg intravenous and 50 mg oral doses of trazodone were given to 43 healthy subjects, divided into young men and women (aged 18 to 40 years) and elderly men and women (aged 60 to 76 years). Among men, trazodone volume of distribution (V area ) was increased in elderly vs. young subjects (1.15 vs. 0.89 L/kg; P < 0.05), and clearance decreased (1.65 vs. 2.31 ml/min/kg; P < 0.05), thereby increasing elimination half‐life (t ½ ) in elderly men (8.2 vs. 4.7 hours; P < 0.001). V area in women was also increased in the elderly (1.5 vs. 1.27 L/kg; P < 0.02), causing increased t ½ (7.6 vs. 5.9 hours; P < 0.05), but clearance was unrelated to age. Absolute bioavailability of oral trazodone averaged 70% to 90% and was unrelated to age or sex. In 23 obese subjects (mean weight 112 kg) vs. 23 matched control subjects of normal weight (mean 65 kg), V area was greatly increased (162 vs. 67 L; 1.43 vs. 1.04 L/kg; P < 0.001) and was highly correlated with body weight (r = 0.91). Clearance was unchanged between groups (146 vs. 136 ml/min), but the increased V area caused prolonged t ½ in obese subjects (13.3 vs. 5.9 hours; P < 0.001). Reduced clearance of trazodone among elderly men may indicate a need for dosage reduction during chronic therapy. In obese individuals, choice of dosage during chronic treatment should be based on ideal rather than total body weight. Clinical Pharmacology and Therapeutics (1987) 42, 193–200; doi: 10.1038/clpt.1987.132