This chapter deals with interactions which occur before pharmaceutical interactions and during pharmacokinetic interactions absorption. The delivery of drugs into the circulation may be altered by physicochemical interactions that occur prior to absorption. Several drugs can interfere with the physiologic conditions and function of the gastrointestinal tract, and therefore alter the absorption of other drugs. Phenytoin is the most studied of the antiepileptic drugs (AEDs), principally because it has been in use the longest. Food has been found to have variable but modest, usually enhancing, effects on phenytoin absorption. Epileptic patients receiving phenytoin have been reported to exhibit a significantly smaller diuretic response to furosemide. The gastrointestinal absorption of carbamazepine formulations is slow, erratic and unpredictable. Over the past few years, eight new AEDs felbamate, gabapentin, lamotrigine, oxcarbazepine, topiramate, zonisamide, vigabatrin, and levetiracetam have reached the market and are licensed for clinical use.