Summary of Studies Showing Age-Differences in Pharmacokinetics: Psychoactive Medications
Risperidone is a commonly used antipsychotic agent with anticholinergic properties. Both risperidone and its 9-hydroxyrisperidone metabolite are active. In a study of 129 adults on risperidone maintenance therapy grouped by age (<45, 45-60 and >60 years), the risperidone maintenance dose was lowest in the oldest age group, but the unadjusted plasma risperidone concentrations did not differ significantly across age groups. However, when adjusted for subject body weight or maintenance dose the plasma risperidone concentration was significantly higher in the older group. The concentration of active drug was comprised of both the 9-hydroxyrisperidone metabolite and risperidone parent drug, with the difference driven by the 9-hydroxyrisperidone concentration115. This supports the use of the lowest dose possible of risperidone in older adults and provides support for a “start low and go slow” approach to antipsychotic dosing in geriatric populations. In comparison, the clearance of the sedative diazepam was not found to be affected by age in a study of young (21-30 years) males and females in comparison to older males and females (70-88 years)78. A naturalized study of multiple anticholinergic antidepressants showed an increase in the absolute serum concentrations to dose adjusted serum concentrations for fluvoxamine (2-fold), amitriptyline and clomipramine (1.5-fold) in the oldest age group more than 65 years of age in comparison to controls less than 40 years. No significant age difference was observed for the dose adjusted fluoxetine and trimipramine serum concentrations. For fluoxetine and trimipramine users, older adults were using 10-30% lower total daily doses. The concentration to dose ratio of nortriptyline was two-fold higher in adults over 65 in comparison to the controls less than 40 years old 80; clearance was correlated with age with faster clearance at younger ages. No significant difference was found between patients younger or older than 60 years in the mean dose-corrected serum concentration of clomipramine and N-clomipramine, which contradicts the findings of Waade82. However amitriptyline plasma levels were higher in older adults than younger subjects89 which was consistent with findings of Waadeet al. and Dawling et al . who showed that both amitriptyline and nortriptyline levels were higher in older adults with older women experiencing a more exaggerated effect than their male comparators116. At daily oral doses of 100 mg or 200 mg, fluvoxamine serum concentration did not correlate with age84. There was a trend to higher serum concentrations in older female patients with the lower dosage, but this diminished when the dosage was doubled and suggests there is an interaction between age and sex on fluvoxamine pharmacokinetics. Older subjects taking oral paroxetine had higher plasma concentrations than younger subjects117. In a study that examined bupropion kinetics in older adults with depression (mean age 71.5 years) clearance was 80% of that seen in younger adults88and t1/2 was 34 hours in comparison to most sources which report 11-14 hours88,118. Among females, there was no significant difference between young and older groups in any of the pharmacokinetic variables for triazolam. Among males, the t1/2 of triazolam increased. Furthermore, when age was evaluated as a continuous variable, AUC increased significantly with age (p = 0.02) and clearance decreased with age (p = 0.02). Further examination of cyclobenzaprine pharmacokinetics showed increased t1/2 in older vs. younger adults77.