Variability of Serum Phenytoin Concentrations in Nursing Home Patients

The Current State of Knowledge on Age, Sex, and Their Interactions on Clinical Pharmacology

“…Effects of inducers and inhibitors were not detected. There was marked variability in concentrations in residents with repeated measurements at the same dosage, similar to earlier observations in elderly patients 78 , 79 , 80 . Preliminary data from investigations of stable labeled phenytoin and fos‐phenytoin administered to adults ( n =8, aged 18–64 years) and elderly patients over the age of 65 years ( n =21), during steady‐state dosing of phenytoin and not receiving known interacting medications, found that the elderly took smaller doses and had lower total and unbound serum phenytoin concentrations compared with adults; elimination half‐lives were similar but distribution volume, unbound fraction, and total and unbound phenytoin clearance tended to be higher in the elderly than in the young 81 .…”

“…Preliminary data from investigations of stable labeled phenytoin and fos‐phenytoin administered to adults ( n =8, aged 18–64 years) and elderly patients over the age of 65 years ( n =21), during steady‐state dosing of phenytoin and not receiving known interacting medications, found that the elderly took smaller doses and had lower total and unbound serum phenytoin concentrations compared with adults; elimination half‐lives were similar but distribution volume, unbound fraction, and total and unbound phenytoin clearance tended to be higher in the elderly than in the young 81 . These preliminary data in combination with the patient studies 78 , 79 , 80 suggest either differing age‐related effects, unrecognized environmental effects, pharmacogenetic variation, or greater variability in age‐related effects than reported in earlier studies of age‐related changes in healthy people. It appears that age‐related decreases in clearance may not be as great as predicted from investigations of age effects in healthy subjects, stressing the need for monitoring of drug concentrations and/or drug effects in the clinical setting.…”

Variability of total phenytoin serum concentrations within elderly nursing home residents

“…That study found a remarkably large intraresident variability in serial total PHT concentrations over time without dose changes. 12 Our study was part of an NIH-supported program project investigating epilepsy in the elderly and involved subjects from 112 nursing homes throughout the United States. This is a preliminary report that presents data from a subset of residents who were on the same dose of PHT.…”

“…It reinforces a previous report of variability in 15 individuals (aged 46 to 90 years) from a single nursing home. 12 Although the individuals' charts were examined in the previous study, no single factor could be identified by the author that would explain the variability. This study included residents from 32 different nursing homes.…”

Ultra‐deep sequencing analysis of resistance‐associated variants during retreatment with simeprevir‐based triple therapy after failure of telaprevir‐based triple therapy in patients with genotype 1 hepatitis C virus infection

“…To validate the error rates in the PCR and sequencing approaches, we carried out control experiments using a plasmid encoding a wild‐type HCV sequence in each of the three runs. The error rate was not uniform across sites . Therefore, cut‐off values for the detection of variants were defined to be greater than the mean frequency plus doubled standard deviations of the mismatch error (non‐synonymous amino acid substitution) per amino acid position (Table S1).…”