Free Drug Metabolic Clearance in Elderly People

  title={Free Drug Metabolic Clearance in Elderly People},
  author={Jennifer M. Butler and Evan James Begg},
  journal={Clinical Pharmacokinetics},
The question of whether metabolic drug clearance is decreased in elderly people has been the subject of considerable debate and is very important because clearance is a determinant of dosing. Drug clearance has been shown to be consistently impaired for flow-limited (high-clearance) drugs, but there have been conflicting results for capacity-limited (low-clearance) drugs. A limitation of the studies of capacity-limited drugs is that most have estimated clearance based on total drug… 

The 'apparent clearance' of free phenytoin in elderly vs. younger adults.

This research does not prove the hypothesis that the 'apparent clearance' of free phenytoin is reduced in the elderly, but trends found are supported by trends in the same direction in other published studies, suggesting an age effect.

Pharmacokinetics and drug metabolism in the elderly

  • U. Klotz
  • Medicine, Biology
    Drug metabolism reviews
  • 2009
In the elderly, hepatic drug clearance of some drugs can be reduced and CYP-mediated phase I reactions are more likely to be impaired than phase II metabolism, which is relatively preserved in the elderly.

Predicted metabolic drug clearance with increasing adult age.

Physiological parameters that determine CLPT decreased with increasing adult age: mean microsomal protein g of liver, liver weight, hepatic blood flow and human serum albumin concentration, which may be increasingly useful in predicting metabolic drug clearance in the elderly.

Age-related changes in pharmacokinetics Drugs Age-Related Effects on Pharmacokinetics

The analysis of NEPharm records revealed an average age-related prolongation of half-life of 1.39-fold (corresponding to 39 61%).

Drug metabolism in older people--a key consideration in achieving optimal outcomes with medicines.

  • A. McLachlanL. Pont
  • Medicine, Biology
    The journals of gerontology. Series A, Biological sciences and medical sciences
  • 2012
There is growing evidence that the age-related changes in the liver not only result in a decrease in the hepatic clearance of unbound drug but also influence variability in response to medicines in older people.

Apparent clearance of valproic acid in elderly epileptic patients: estimation of the confounding effect of albumin concentration

Total VPA concentrations should be interpreted with caution, mainly in older patients, in which determination of unbound or normalized total drug concentrations may be clinically useful.

Review on pharmacokinetics and pharmacodynamics and the aging kidney.

The analysis of NEPharm records revealed an average age-related prolongation of half-life of 1.39-fold (corresponding to +39 +/- 61%).

Age-related pharmacokinetic and pharmacodynamic changes and related risk of adverse drug reactions.

Age-related changes in pharmacokinetics and pharmacodynamics, together with comorbidity and polypharmacy, make elderly patients at special risk for adverse drug reactions, which in turn are cause of relevant health burden and costs.

Free Drug Monitoring

There is a need for monitoring free drug concentrations in patients with hypoalbuminemia and critically ill patients due to elevated concentrations of free levels of drugs secondary to impaired protein binding as well as displacement of certain drugs from protein binding by ceratin uremic toxins.

Clinical pharmacokinetics of antiretroviral drugs in older persons

The evidence to date does not support major pharmacokinetic changes in adults between ∼ 20 and 60 years of age, and guidelines for drug–drug interactions and dosing in renal and hepatic impairment should be followed in older HIV-infected individuals.



The Aging Liver

A review of age-related change in drug clearances established that patterns of change are not simply explained in terms of hepatic blood flow, hepatic mass and protein binding changes, and the reduction in clearances of high extraction drugs does correlate with observed reduction in hepatic perfusion.

Dose-Related Pharmacokinetics and Pharmacodynamics of Valproate in the Elderly

Significant dose-dependent changes in valproate pharmacokinetics were observed in the elderly and the impact of this on drug-related side effects using a single-blind within-subject study design in healthy elderly volunteers.

Drug Therapy in the Elderly

Pharmacokinetics of calcium blockers in patients with renal insufficiency and in geriatric patients.

Findings imply that verapamil dosage should be reduced in patients with impaired renal function and elderly patients, and that the biologic availability in the elderly was higher than in younger persons.

Rationale for Monitoring Free Drug Levels

Free level monitoring should be considered for drugs for which the usefulness of plasma level monitoring has been established, drugs which are highly bound to plasma proteins, and which exhibit a variable free fraction.

Pharmacokinetics of high-dosage naproxen in elderly patients.

It is, therefore, advisable to start treatment with naproxen in the elderly at a low dosage, as age-related factors increase serum unbound Naproxen concentrations.

Hepatic Drug Metabolism and Aging

Although there is considerable variation in the effect of age on drug biotransformation, the metabolism of many drugs is impaired in the elderly, and initial doses of metabolised drugs should be reduced in older patients and then modified according to the clinical response.

Naproxen pharmacokinetics in the elderly.

Since it is the unbound drug concentration which appears in general to relate more closely to pharmacological and toxic effect, it may be advisable to reduce naproxen doses by half in the elderly, pending plasma drug concentration-response studies in this age group.

Drug Dosage in the Elderly

The increased responsiveness to drugs in the elderly renders the measurement of drug plasma concentrations an attractive method to monitor pharmacotherapy in this age group and Investigations concerning drug pharmacokinetic-pharmacodynamic relationships in the aged are an important area of future work in clinical pharmacology.

The pharmacokinetics of piroxicam in elderly persons with and without renal impairment.

There were significant reductions in clearance and clearance of unbound piroxicam between single and chronic doses and Elimination half-lives, steady state concentrations of piroXicam and 5'-hydroxypiroxICam, clearances of total and un bound pirozicam, volumes of distribution normalized for body weight, and urinary recovery were not influenced by age or renal function.