Bioavailability of phenytoin: clinical pharmacokinetic and therapeutic implications

Phenytoin (diphenylhydantoin) is still the most commonly used anticonvulsant drug. It has certain physicochemical characteristics which make it liable to bioavailability problems. Due to the dose dependent metabolism of phenytoin and to its narrow therapeutic range even small changes in the bioavailability can cause major changes in serum phenytoin concentration and have serious clinical consequences. Numerous studies have demonstrated that there are products in general use with considerable differences in their bioavailiability. If the epilepsy is well controlled, a change from one phenytoin product to another should be avoided. Such a change might lead to phenytoin intoxication or to poor control of epilepsy, if the products do not have the same bioavailability. There seems to be no systematic difference in the bioavailability of phenytoin sodium and phenytoin acid, if products of high quality are used. On the other hand, various biopharmaceutical factors, e.g. particle size of phenytoin and the nature of excipients in the product, can have a marked effect on the oral absorption of phenytoin. Gastrointestinal diseases, the concomitant use of other drugs and dietary factors might also modify the bioavailability of phenytoin. The absorption of intramuscularly given phenytoin is rather slow and erratic. The existence of phenytoin products with different bioavailability is a serious practical problem which should be corrected as soon as possible.