Phenotyping CYP2D6 in frail elderly by a 13C-dextromethorphan breath test

Older people display considerable variability in efficacy and adverse effects
of medicines. A person*s response to medication depends on the pharmacokinetic
and pharmacodynamic properties of a specific drug in a specific patient.
The pharmacokinetics and pharmacodynamics of a drug are in turn influenced by
pathological and clinical factors associated with comorbidity, concomitant use
of drugs, and age-related changes in organ function. Frailty is a clinical
phenotype that is associated with adverse health outcomes and is characterized
by an excessive reduction of lean body mass, sarcopenia, chronic
under-nourishment, reduced function, and poor endurance . Frailty is likely to
increase the age-related heterogeneity in the pharmacokinetics and
pharmacodynamics of drugs.CYP2D6 is the most important isozyme in the
metabolism of a variety of drugs such as betablockers, antipsychotics (like
haloperidol) most selective serotonin reuptake inhibitors (SSRIs), and
antitumour agents like tamoxifen and gefitinib.
To date, no phenotype studies have been reported on CYP2D6 activity and
frailty.

-The primary objective is to compare the CYP2D6 phenotype, determined by DM-BT
in frail and non-frail elderly (by using Fried definition).
-The secondary objective is to correlate individual parameters of frailty (e.g.
grip strength) with CYP2D6 phenotype, determined by a 13C-dextromethorphan
breath test (DM-BT)

Pharmacokinetic intervention study

Assesment of CYP2D6 phenotype by 13C-dextromethorphan breath test

Adverse events to dextromethorfan are mostly very mild and selden occur to
happen. Dextromethorfan has been registered in the Netherlands (over the
counter status).