The Effect of Age on Pharmacokinetics of Antiepileptic Drugs

Lj, Willmore

doi:10.1111/j.1528-1157.1995.tb06005.x

Cited by 35 publications

(13 citation statements)

References 62 publications

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“…■ Considerations related to the elderly Elderly patients have an increased sensitivity to the effects of AEDs due to pharmacokinetic as well as pharmacodynamic changes [51]. Adverse effects are more frequent and occur at lower dosages but elderly patients also seem to achieve seizure control at lower dosages than other age groups [29,41,42].…”

Section: ■ Gender Related Considerationmentioning

confidence: 99%

Drug selection for the newly diagnosed patient: When is a new generation antiepileptic drug indicated?

Tomson

2004

J Neurol

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Treatment options in epilepsy have increased dramatically since the early 1990s with the introduction of nine new generation antiepileptic drugs (AEDs) (felbamate, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, tiagabine, topiramate, vigabatrin and zonisamide). This makes drug selection much more complicated and challenging. This review discusses drug selection in patients with newly diagnosed epilepsy and in particular the role of new AEDs in this population. The choice of treatment should always be based on a careful comparison of the risk-benefit ratio for the different treatment options and the outcome of such evaluation may be different in patients with new onset compared with chronic epilepsy. Efficacy, tolerability and safety are the main criteria for selection of AEDs and any first line drug for patients with newly diagnosed epilepsy must have demonstrated satisfactory efficacy as monotherapy in that patient population. So far, of the new AEDs only lamotrigine, oxcarbazepine and topiramate have documentation sufficient to be granted licence for use as monotherapy in most European countries. Because the new generation AEDs have failed to demonstrate improved effectiveness as monotherapy, old generation AEDs such as carbamazepine and valproate remain drugs of first choice for partial and generalised seizures, respectively. However, there are special situations and populations where a new AED may be a reasonable first line drug. These include vigabatrin in West syndrome associated with tuberous sclerosis, lamotrigine as alternative to valproate in idiopathic generalised seizures in women of childbearing potential and lamotrigine for the treatment of epilepsy in the elderly population. The role of the new generation AEDs is likely to become more prominent as more experience is gained.

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Section: ■ Gender Related Considerationmentioning

confidence: 99%

Drug selection for the newly diagnosed patient: When is a new generation antiepileptic drug indicated?

Tomson

2004

J Neurol

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“…The etiology of prerenal azotemia in the hospitalized elderly patients, in order of decreasing frequency, includes volume contraction, uncontrolled congestive heart failure, and drugs such as nonsteroidal anti-inflammatory drugs (NSAIDs), angiotensin-converting enzyme inhibitors, diuretics, and antibiotics [5,[50][51][52][53].…”

Section: Drug-induced Acute Nephropathymentioning

confidence: 99%

Age-Dependent Changes of the Kidneys: Pharmacological Implications

Mühlberg

Platt²

1999

Gerontology

226

105

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About 40% of the intoxications after drug administration occur in the elderly. A significant proportion of the disease states in elderly patients is related to adverse reactions to prescribed drugs. Declining renal function, a reduction in both renal blood flow and glomerular filtration rate, is a major contributor to drug toxicity in the elderly. Therefore, a review (based on newer papers from Medline) of age-dependent changes of the kidneys and their consequences for drug therapy in geriatric patients is presented. Renal changes that occur with aging are: a decrease of renal weight, a thickening of the intrarenal vascular intima, sclerogenous changes of the glomeruli, and infiltration of chronic inflammatory cells and fibrosis in the stroma. Altered renal tubular function, including impaired handling of water, sodium, acid, and glucose, is also frequently present in old age. Impaired ‘endocrinologic’ functioning manifested by changes of the renin-angiotensin system, vitamin D metabolism, and antidiuretic hormone responsiveness has been reported. The aging kidney is constantly exposed to the effects of a variety of potential toxic processes, i.e., drugs and chronic illnesses including hypertension, diabetes, and atherosclerotic disease. Renal changes that occur with aging also consist of impairment in the ability to concentrate urine and to conserve sodium and water. These physiological changes increase the risks of volume depletion and prerenal type of acute renal failure. A frequent cause of acute renal failure in the elderly is drug-induced nephropathy. Nonsteroidal anti-inflammatory drugs, antibiotics, and diuretics are most often involved. Due to the age-dependent decline of renal function, the pharmacokinetics of many drugs are altered in elderly patients. Therefore, the most important renal function to monitor with aging is the creatinine clearance. Changes in pharmacokinetics of many drugs and most decisions on drug dosage can be based on this information alone, as tubular functions of the kidney decrease at rates paralleling the age-dependent decrease in glomerular filtration rate (which is approximately measured by the creatinine clearance). As a conclusion, age-dependent changes of renal function are not only responsible for changes in pharmacokinetics and pharmacodynamics. In many cases, the kidneys are the target organ of adverse drug reactions too.

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“…However, we decided to focus on the geriatric patient population ( ≥ 60 years) due to the fact that this segment of patients is largely ignored and faces tremendous problems with [25]. Further, elderly patients may become more susceptible to the adverse effects of medications due to their diminished physical reserve [7][8].…”

Section: Discussionmentioning

confidence: 99%

“…Drug-related factors that change with age include efficacy, pharmacokinetics, co-medications and medication side effect profiles [4,8]. Indeed, the medication regimen in the geriatric population is often complicated by three main challenges; namely, heightened sensitization to drug action, reduction in physiological elimination function and poly-pharmacy which may lead to drug-drug interactions or reduced drug absorption [9].…”

Section: Introductionmentioning

confidence: 99%