Failure to detect a relationship within a selected sample does not establish that the relationship is absent across all patients. This matters when an older-adult pharmacokinetic study is used to dismiss renal function as a consideration in interpreting amphetamine exposure.
What population received the dose?
Ermer and colleagues’ 2013 double-blind crossover study enrolled 47 healthy adults aged 55 years or older. Participants received single oral lisdexamfetamine 50 mg and placebo doses, separated by 7–14 days. The age groups were 55–64, 65–74 and at least 75 years. Mean baseline creatinine clearance was within the normal range in every group.
Active d-amphetamine exposure was modestly higher and clearance slower in the oldest group. Among women, mean peak plasma concentration was 51.0 ± 6.7 ng/mL at ages 55–64 versus 64.3 ± 12.1 ng/mL at ages at least 75; median peak times were 3.5 and 5.5 hours. The reported spreads are standard deviations.
The study found no relationship between d-amphetamine clearance and baseline creatinine clearance, and no consistent age pattern in pulse or blood-pressure changes. It excluded important comorbidities and did not represent medically complex older patients.
The age comparison was not randomized
Randomization determined treatment sequence, rather than age. The crossover strengthened the comparison between the administered treatments, but it did not randomly assign people to different ages. An observed age pattern therefore should not be described as an isolated experimental effect of aging.
Likewise, the renal finding concerns the range represented in the enrolled group. A conclusion that kidney function never affects amphetamine disposition would extend the inference beyond that range. It would require evidence from participants with the relevant degrees of impairment, rather than a null association in a healthy sample.
Can these concentrations predict an individual’s functioning?
The reported values describe concentration–time profiles after a known dose under study conditions. They do not provide a validated impairment threshold. A person’s measured concentration should not be matched to an age-group mean and then assigned the group’s presumed behavior.
Peak timing also deserves attention. A specimen collected at a particular hour is an observation at that hour. Comparing it with a study’s maximum concentration requires establishing how sampling time relates to administration and the observed curve, rather than assuming the sample coincided with the peak.
The useful application is to frame questions about age, specimen timing and the applicability of the comparison population. This historical single-dose study cannot establish dose proportionality in older adults, chronic safety or a dosing rule for patients with significant renal or hepatic dysfunction.
Source
Ermer J, et al. Double-blind, placebo-controlled, two-period, crossover trial to examine the pharmacokinetics of lisdexamfetamine dimesylate in healthy older adults. Neuropsychiatr Dis Treat. 2013;9:219–229. doi:10.2147/NDT.S38377. Full text.