Barbiturates: PK in the elderly

Advanced, Clinical Subspecialties

Pharmacokinetics – or what the body does with a drug – involves drug absorption, volume of distribution, metabolism (and half-life), and clearance. Phenobarbital is rapidly absorbed orally, is metabolized in the liver by oxidation primarily via CYP2C9, and is ultimately excreted primarily in the urine and minimally in the feces. Regarding the pharmacokinetics of phenobarbital in the elderly, a study published in 2005 examined clearance values in 224 patients aged 65-90 years old and found that serum levels of phenobarbital were equivocal in the elderly vs. non-elderly patients (aged 20-50 years old); however, the clearance to bioavailability (CL/F) values were on average 22% lower in the elderly patient group. Thus compared to the non-elderly, elderly patients require lower doses of phenobarbital to achieve a similar serum concentration. 

Of note, this study demonstrated some variability between individuals, and thus certain data did not reach statistical significance. Interestingly, the coadministration of other antiepileptic drugs (specifically carbamazepine and phenytoin) also plays a significant role in reducing phenobarbital clearance in the elderly. Overall the likely explanation for reduction in clearance in the elderly is a physiologic decrease in GFR – and thus decreased excretion of both metabolized and unchanged drug – as well as decreased hepatic metabolism by CYP2C9.


    Epilepsia;2005 Mar;46(3):372-7

    [PubMed: 15730534]


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Kathryn Kirkpatrick, MD