Role of phenytoin in wound healing--a wound pharmacology perspective

Topical agents used for the enhancement of wound healing are designed to act locally and, therefore, do not undergo classic systemic metabolic modification. This commentary reviews the potential role of a vulnerary agent, phenytoin, (PHT), from a wound pharmacology perspective. This agent may have the potential to alter the dynamics of wound healing, suggesting a therapeutic use for the stimulation of chronic wounds. Oral PHT therapy is used widely for the treatment of convulsive disorders, and about half the patients treated develop gingival overgrowth as a side-effect. This apparent stimulatory effect has prompted its assessment in wound healing. Investigations into the mechanisms of gingival overgrowth also provide clues to its action in wound healing, and important similarities and differences are discussed. It appears also that both gingiva and skin are important extrahepatic sites for xenobiotic metabolism, and analysis of the biochemical mechanisms should lead to the design of safer analogues for wound healing. On the other hand, differences between the pharmacokinetics of topical PHT in these tissue situations indicate that different formulations are required for gingival and cutaneous wound healing and during the changing course of wound healing itself.