Does Age Change Carbamazepine Pharmacokinetics?

Elderly patients taking carbamazepine in conjunction with phenytoin experience a reduced increase in carbamazepine levels, a study finds.

Carbamazepine is the most frequently prescribed antiepileptic drug (AED) for elderly patients, despite data that indicates that elders tolerate the AEDs lamotrigine and gabapentin better. The pharmacokinetics of carbamazepine are complex, and several factors—absorption variability, protein binding, therapeutic index, and enzyme induction—may contribute to altered pharmacokinetics as patients age.

Researchers from the University of Minnesota and colleagues investigated carbamazepine’s pharmacokinetic parameters and the parameters’ variability in 121 patients aged 60 to 69 years. The researchers, who published their results in the April 2012 edition of Therapeutic Drug Monitoring, gathered 555 plasma samples from the patients and found that the most significant influence on carbamazepine clearance was concurrent phenytoin use. Body size, age, race, and organ impairment, by contrast, had no effect on clearance.

The researchers also found that in their elderly participants, concurrent phenytoin increased carbamazepine clearance less than had been previously identified in younger adults. Studies have demonstrated that in younger adults, concurrent phenytoin and carbamazepine increased carbamazepine levels approximately 44%. In the current study of elders, the combination increased carbamazepine levels just 23%. This suggests that dose modifications in elders who need both carbamazepine and phenytoin may need to be smaller than in younger adults. As possible causes for the different results, the researchers proposed bioavailability, hepatic enzyme activity, and carbamazepine metabolism autoinduction changes.

Ms. Wick is a visiting professor at the University of Connecticut School of Pharmacy and a freelance writer from Virginia.