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.