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

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

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)372-377
Number of pages6
Issue number3
Publication statusPublished - Mar 2005


  • Elderly
  • Epilepsy
  • Pharmacokinetics
  • Phenobarbital
  • Therapeutic drug monitoring

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)


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