Phenobarbital pharmacokinetics in old age: a case-matched evaluation based on therapeutic drug monitoring data

To assess the influence of aging on the pharmacokinetics of phenobarbital (PB) at steady state in patients receiving long-term therapy.

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.

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).

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.