Evaluation of wound healing activity of topical phenytoin in an excision wound model in rats

Sarita Mulkalwar, Lopamudra Behera, Pravin Golande, Rahul Manjare, Harshal Patil


Background: Wound healing is a significant healthcare problem in today’s medical practice. Despite extensive treatment modalities that are supposed to hasten the wound healing process, the outcomes of existing methods are far from optimal. One such agent that has been tried previously and found controversial in wound healing is phenytoin. Therefore, this study was planned to evaluate and compare wound healing effect of topical phenytoin with povidone iodine ointment in rats.

Methods: This study was conducted after approval from Institutional Animal Ethics Committee (IAEC). Wound healing activity of topical phenytoin (1 g% and 2 g%) was assessed in excision wound model in Sprague Dawley rats (n=8), which was compared with topical petroleum jelly and povidone iodine ointment. Parameters studied included wound area on day 0, 4, 8, 12, 16, 20, percentage wound contraction, percentage wound healing from day 0 to day 20 and period of re-epithelisation.

Results: Wound surface area decreased in all treatment groups from day 0 through day 20 and the percentage wound closure was better in both the preparations (1% and 2%) of phenytoin when compared wih control and povidone iodine, but this was not statistically significant. Furthermore, the days required for complete re-epithelisation were less with phenytoin treated groups. There was no statistical difference between both the preparations of phenytoin.

Conclusion: In this study, it was found that topical phenytoin accelerates wound healing process in an excision wound model.


Epithelization, Phenytoin, Wound contraction

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Earley MJ. Wound, tissue repair and scars. In: Williams NS, Christopher JKB, editors. Baieley and Loves: Short Practice of Surgery. 25th Edition, Volume. 3. London: Edward Arnold Publishers Limited; 2008: 24-5.

Hasamnis A, Mohanty B, Muralikrishna, Patil S. Evaluation of wound healing effect of topical phenytoin on excisional wound in albino rats. J Young Pharm. 2010;2(1):59-62.

Deshmukh VS, Motghare VM, Padwal SL, Jadhav RR, Rathod SS, Jadhav AD, et al. Effect of phenytoin on wound healing in albino rats. Int J Exp Pharmacol. 2014;4(1):4-7.

Daunton C, Kothari S, Smith L, Steele D. A history of materials and practices for wound management. Wound Prac Res. 2012;20:174-86.

Vogel WE, Vogel WH, Sandow J, Muller G. Healing of skin wounds. Drug Discovery and Evaluation. Volume 11. Berlin: Springer Publishing Company; 1999: 1360-2.

Kimball OP, Horan TN. The use of Dilantin in the treatment of epilepsy. Ann Intern Med. 1939;13:787-93.

Shapiro M. Acceleration of gingival wound healing in non-epileptic patients receiving diphenylhydantoin sodium (dilantin, epanutin). Exp Med Surg. 1958;16(1):41-53.

Goebel RW. Sodium diphenylhydantoin association with oral healing. J Oral Surg. 1972;30(3):191-5.

Shafer WG, Beatty RE, Davis WB. Effect of dilantin sodium on tensile strength of healing wounds. Proc Soc Exp Biol Med. 1958;98(2):348-50.

Bhatia A, Prakash S. Topical phenytoin for wound healing. Dermatol Online J. 2004;10(1):5.

el Zayat SG. Preliminary experience with topical phenytoin in wound healing in a war zone. Mil Med. 1989;154(4):178-80.

Lodha SC, Lohiya ML, Vyas MC, Bhandari S, Goyal RR, Harsh MK. Role of phenytoin in healing of large abscess cavities. Br J Surg. 1991;78(1):105-8.

Muthukumarasamy MG, Sivakumar G, Manoharan G. Topical phenytoin in diabetic foot ulcers. Diabetes Care. 1991;14(10):909-11.

Pendse AK, Sharma A, Sodani A, Hada S. Topical phenytoin in wound healing. Int J Dermatol. 1993;32(3):214-7.

Modaghegh S, Salehian B, Tavassoli M, Djamshidi A, Rezai AS. Use of phenytoin in healing of war and non-war wounds. A pilot study of 25 cases. Int J Dermatol. 1989;28(5):347-50.

Qunaibi EA, Disi AM, Taha MO. Phenytoin enhances collagenization in excision wounds and tensile strength in incision wounds. Pharmazie. 2009;64(9):584-6.