Antiepileptic drug formulation and treatment in the elderly: biopharmaceutical considerations.

The pharmacokinetics of antiepileptic drugs (AEDs) determine their effectiveness in the treatment of patients with epilepsy. Given the likelihood of comorbid medical conditions that require polytherapy, as well as the normal physiological changes associated with aging, an understanding of AED pharmacokinetics and pharmacodynamics in the elderly patient is critical. There is a relative sparsity of data regarding changes in the oral absorption patterns of AEDs that may accompany aging. Therefore, the objective of this chapter is to discuss fundamental principles related to oral drug absorption, and to discuss their potential impact on AED treatment in the older patient. Although most drugs are absorbed via the diffusion process, active transport also plays a role in absorption. While the gastrointestinal tract shows remarkable resilience during aging, physiological changes that influence oral and esophageal function, gastric pH, gastric emptying rates, and intestinal transit times do occur. Oral administration of AEDs may be affected by changes associated with aging, including altered oral protective reflexes, xerostomia, thickening of the esophageal smooth muscle layer, reduced contraction velocity and duration, altered esophageal emptying rates, and enteric plexus neuron reduction. Gastric acid secretion is similar between older and younger patients, but older patients require more time to return to baseline gastric pH values and have prolonged gastric emptying rates compared to younger patients. Elderly patients may similarly have reduced numbers of myenteric neurons, decreased postprandial contractions, reduced frequency of migrating motor complex, and diminished rectal compliance as well as reduced sphincter tones. All of these effects observed in the aging patient, in turn, produce numerous opportunities for changes in AED absorption, particularly for those agents demonstrating poor water solubility or variable absorption patterns.