Trazodone kinetics: Effect of age, gender, and obesity

Abstract

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 (Varea) was increased in elderly vs. young subjects (1.15 vs. 0.89 L/kg; P less than 0.05), and clearance decreased (1.65 vs. 2.31 ml/min/kg; P less than 0.05), thereby increasing elimination half-life (t1/2) in elderly men (8.2 vs. 4.7 hours; P less than 0.001). Varea in women was also increased in the elderly (1.5 vs. 1.27 L/kg; P less than 0.02), causing increased t1/2 (7.6 vs. 5.9 hours; P less than 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), Varea was greatly increased (162 vs. 67 L; 1.43 vs. 1.04 L/kg; P less than 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 Varea caused prolonged t1/2 in obese subjects (13.3 vs. 5.9 hours; P less than 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.

Drug Disposition in Obesity: Toward Evidence-Based Dosing

“…For midazolam, no difference in bioavailability was found between normal-weight volunteers (66 ± 2 kg, n = 20) and obese volunteers (117 ± 8 kg, n = 20) (40 ± 3% versus 42 ± 4%, P > 0.05, respectively), nor was a difference found in time of maximum concentration (T max ) or maximum concentration (C max ) itself (81). Similarly, no difference in bioavailability or oral absorption rate was found for trazodone, cyclosporine, dexfenfluramine, and moxifloxacin between obese and nonobese subjects (82)(83)(84)(85).…”

“…Only six studies have directly compared the oral bioavailability and absorption rate of drugs between obese and nonobese subjects on the basis of both oral and intravenous administration (80)(81)(82)(83)(84)(85). For propranolol, clearance (CL) after an intravenous dose was not different between six obese (136 ± 36 kg) and six control (67 ± 5 kg) subjects.…”

Evaluation of postmortem redistribution phenomena for commonly encountered drugs

“…Studies on amitriptyline [4,18,28,31,33,34,54,55], carbamazepine [28,30,31,36,37], tramadol [22,46,[56][57][58][59] and trazodone [47][48][49][60][61][62][63] related deaths and PMR have frequently been reported. Propofol related deaths [64][65][66][67][68][69] have frequently been reported, but studies on PMR of propofol have not been reported.…”

Sex differences in pharmacokinetics of antidepressants

“…dose of trazodone identified that women had a higher distribution volume irrespective of age. Also, clearance was unaffected by age in women but not in men and elimination half-life was longer in young women than in young men, but shorter in elderly women than in elderly men [125].…”