Absorption and Safety of Topically Applied Timolol for Treatment of Chronic Cutaneous Wounds

Abstract

Objective: There are no safety or absorption studies to guide topical timolol therapy for treatment of chronic wounds. This study was undertaken to address this gap. Approach: A prospective, observational, cross-sectional comparative study of timolol plasma levels in patients after topical administration to a chronic wound, compared with levels in patients after timolol ocular administration for the indication of glaucoma. Results: There was no statistically significant difference in the average plasma level of timolol in wound as compared with glaucoma patients. No bradycardia or wheezing was observed after administration. Innovation: We determined the single time point concentration of timolol in plasma 1 h after application of timolol 0.5% gel-forming solution to debrided chronic wounds, providing insight as to the safety of this emerging off-label treatment. Conclusion: The topical application of timolol for chronic wounds shares the same safety profile as the widely used application of ocular administration for glaucoma.

Keywords: absorption; adrenergic receptor; catecholamine; chronic wounds; glaucoma; timolol.

Copyright 2019, Copyright © 2019 by Mary Ann Liebert, Inc., publishers.

Figures

Roslyn Rivkah Isseroff, MD

Sara Evona Dahle, DPM, MPH

Figure 1.

Systemic levels of timolol in the glaucoma and chronic wound groups. Plasma was collected from the patients in the glaucoma group and the chronic wound group 1 h after administration of topical timolol 0.5% gel-forming solution to the eye or wound surface. Plasma levels were determined as outlined in the Materials and Methods section. Nonparametric analysis was used to report findings. Kolmogorov–Smirnov normal test showed that eye group data were normally distributed (0.200); however, the wound group data were not normally distributed (0.001). The means plasma levels of both groups were not significantly different (p = 0.26).

Figure 2.

Systemic levels of timolol by dose/body weight and by wound type. (A) The administered timolol dose per kg body weight plotted against the systemic plasma timolol level. Linear regression analysis of the data: R-squared, fitness of the data to the regression line is 0.47 in the chronic wound group and 0.01 in the glaucoma group. (B) The mean plasma level of timolol in patients in each category of wound was tallied. The difference in group means is not statistically significant.