Influence of aging on serum phenytoin concentrations: a pharmacokinetic analysis based on therapeutic drug monitoring data

Battino, Dina; Croci, Danilo; Mamoli, Daniela; Messina, Sara; Perucca, Emilio

doi:10.1016/j.eplepsyres.2004.04.006

Cited by 30 publications

(14 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[6][7][8][9]19,20 These studies found that PHT concentration/dose ratios tend to increase with advancing age while protein binding decreases. Some groups have characterized PHT MichaelisMenten parameters, Vmax (maximum rate of metabolism), and Km (concentrations at which metabolism is 50% of maximum), using a single PHT concentration at two different oral maintenance doses.…”

Section: Figure 2 Distribution Of Phenytoin Half-lives In Women (Closmentioning

confidence: 93%

“…The resulting increase in PHT concentrations would explain the lower clearance and Vmax/F reported in some studies. 6,20 In contrast, we directly determined CL using IV injections and measurement of 10 PHT concentrations per subject. Other factors include a failure to account for health status of subjects, medication compliance, drug interactions, and statistical biases in the methods.…”

Section: Figure 2 Distribution Of Phenytoin Half-lives In Women (Closmentioning

confidence: 99%

See 1 more Smart Citation

Phenytoin half-life and clearance during maintenance therapy in adults and elderly patients with epilepsy

Ahn¹,

Cloyd²,

Brundage³

et al. 2008

Neurology

View full text Add to dashboard Cite

show abstract

Section: Figure 2 Distribution Of Phenytoin Half-lives In Women (Closmentioning

confidence: 93%

Section: Figure 2 Distribution Of Phenytoin Half-lives In Women (Closmentioning

confidence: 99%

Phenytoin half-life and clearance during maintenance therapy in adults and elderly patients with epilepsy

Ahn¹,

Cloyd²,

Brundage³

et al. 2008

Neurology

View full text Add to dashboard Cite

show abstract

“…Phenytoin has several pharmacological disadvantages including steep nonlinear kinetics and hepatic enzyme induction 16 . Data from pharmacokinetic analysis in old patients taking phenytoin revealed aging is associated with a gradual decline in AED clearance 34 . Furthermore, as serum albumin level falls gradually with each decade of age 35 , relatively lower phenytoin doses and lower plasma concentrations can be adequate for satisfactory seizure control in elderly patients 36,37 .…”

Section: Pharmacological Changes Of Aeds In the Elderlymentioning

confidence: 99%

Epilepsy in the Elderly

Chen

Cheng

Jou

2012

International Journal of Gerontology

View full text Add to dashboard Cite

s u m m a r y Elderly people are the largest and continuously fastest growing population among patients with epilepsy. Elderly patients with epilepsy are very different from other age groups in many respects and clinicians shouldn't treat them in the same way as younger adults. Accurate diagnosis of epilepsy in the elderly is much more difficult and atypical manifestations and misdiagnoses are certainly not the exception. Syncope is probably the most important differential diagnosis. High clinical suspicion and proper investigation are the best tools for prompt diagnosis. Etiologies of late-onset epilepsy are mainly symptomatic and cerebrovascular diseases are the most common causes in this age group, followed by degenerative diseases such as Alzheimer's disease. It is appropriate to consider starting antiepileptic drug (AED) treatment at the first-ever seizure in elderly patients who have remote symptomatic causes such as stroke and dementia. According to the high recurrence rate of seizure and the good response to AEDs in elderly patients, the proper choice from various AEDs for seizure control is very important. Decisionmaking for AED choice depends on many different factors, including pharmacological properties, efficacy, tolerability from side effects, drug interactions, and medical comorbidities. The newer AEDs with lesser adverse effects and fewer drug interactions appear to be reasonable treatment options for elderly patients. However, more evidence from clinical trials in this specific age group is warranted.

show abstract

“…Because aging is accompanied by a physiologic decrease in glomerular filtration rate, the aging‐associated reduction in PB CL/F rate may be explained, at least in part, by a decrease in renal clearance of unchanged drug, as observed with other AEDs that are eliminated primarily by renal excretion, such as gabapentin (26), levetiracetam (27) and vigabatrin (28). A reduction in metabolic clearance also could contribute to the decrease in CL/F, and it is noteworthy that the unbound drug clearance of AEDs that are eliminated mainly by hepatic metabolism, such as CBZ (18,29), valproic acid (30,31), and PHT (19,32) also has been found to be decreased in elderly patients.…”

Section: Discussionmentioning

confidence: 99%

Phenobarbital Pharmacokinetics in Old Age: A Case‐matched Evaluation Based on Therapeutic Drug Monitoring Data

et al. 2005

Self Cite

View full text Add to dashboard Cite

Summary:Purpose: To assess the influence of aging on the pharmacokinetics of phenobarbital (PB) at steady state in patients receiving long-term therapy.Methods: Serum PB concentrations from the database of the therapeutic drug monitoring service of a large neurological hospital were used to calculate apparent clearance values (CL/F) in 224 patients aged 65 years and older (mean, 73 ± 6.1 years). CL/F values in these patients were compared with those determined in an equal number of controls aged 20 to 50 years (mean, 35.7 ± 7.9 years) and matched for gender, body weight, and type of anticonvulsant comedication. Correlations of CL/F with age, body weight, gender, and comedication also were explored within each age group.Results: PB CL/F values were significantly lower in elderly patients than in controls (3.2 ± 0.8 vs. 4.1 ± 1.2 ml/h/kg; p < 0.0001). Age was identified as a statistically significant predictor of CL/F at multiple regression analysis, but it accounted for only a modest component of the interindividual pharmacokinetic variation. Comedication with carbamazepine (CBZ) and phenytoin (PHT) was associated with a moderate decrease in PB CL/F, which reached statistical significance in the elderly group (p < 0.01 for CBZ comedication; p < 0.001 for PHT comedication).Conclusions: Aging is associated with a significant decrease in PB clearance, which might be related to a reduction in glomerular filtration rate or diminished drug-metabolizing capacity in the liver or both. Because of this, older patients will require lower dosages to achieve serum PB concentrations comparable with those found in nonelderly adults.

show abstract

Influence of aging on serum phenytoin concentrations: a pharmacokinetic analysis based on therapeutic drug monitoring data

Cited by 30 publications

References 36 publications

Phenytoin half-life and clearance during maintenance therapy in adults and elderly patients with epilepsy

Phenytoin half-life and clearance during maintenance therapy in adults and elderly patients with epilepsy

Epilepsy in the Elderly

Phenobarbital Pharmacokinetics in Old Age: A Case‐matched Evaluation Based on Therapeutic Drug Monitoring Data

Contact Info

Product

Resources

About