Metronidazole concentration in the bloodstream following its topical application, at different concentration levels, on experimental skin wounds during healing by secondary intention

Abstract

Purpose To characterize qualitatively and quantitatively the absorption of metronidazole solution, in greater concentrations and for longer periods, when applied topically to an experimental open skin wound model. Methods An open skin wound, 2 cm in diameter and total skin thickness was prepared, under anesthetic, in the dorsal region of 108 Wistar rats weighing between 300 and 350 grams. The animals were allocated to groups of 18 animals in accordance with the concentration of metronidazole in the solution to be applied daily to the wound. In the control group (CG), 0.9% sodium chloride solution was used for application, and in the experimental groups (GI, GII, GIII, GIV and GV) metronidazole solution at 4%, 6%, 8%, 10% and 12%, respectively, was applied. After 3, 7 and 14 days of treatment. Blood samples collected through cardiac puncture were examined for the existence or non-existence of metronidazole, using high performance liquid chromatography (HPLC). Detected metronidazole values were compared statistically within each group (temporal analysis 3 days X 7 days X 14 days) and between the groups that used topical metronidazole (4% X 6% X 8% X 10% and 12%) using the Kruskal-Wallis test, considering a statistical significance of 95% (p<0.05). Results Metronidazole was detected in all the samples at all times in all the groups in which topical metronidazole was applied to the wounds. Characteristically, there was no significant difference between the doses obtained within each group over time (3 days X 7 days X 14 days) GI=0.461; GII=0.154; GIII=0.888; GIV= 0.264 and GV=0.152. In the evaluation between groups, a similar degree of absorption was found after 3 days (p=0.829) and 14 days (p=0.751). Conclusion The serum concentration of metronidazole that was achieved was not influenced by the concentration of the solution applied to the skin wound, with similar extend, or by the duration of the application.

Increased Risk of Bleeding with Topical Metronidazole in a Postoperative Wound after Anal Fistula and Hemorrhoid Surgery: A Propensity Score-Matched Case–Control Study

“…However, these mechanisms apply only to the high serum levels achieved after intravenous or oral dosing. Sampaio CPP et al showed that in experimental rats, the serum concentration of metronidazole following topical application to a skin wound was between 0.001% and 0.002% and was uninfluenced by the concentration, duration and surface area (wound extent) on which TM was applied [ 25 ]. This characterizes an extremely low level of metronidazole in the bloodstream following topical application and does not appear to be responsible for the increased hemorrhagic risk.…”

Fast determination of free metronidazole in rat plasma and peritoneal fluid using HPLC‐UV method

“…In the literature, multiple methods have been described for analyzing MTZ in different biological matrices and with a wide application of HPLC. The quantification of MTZ using HPLC has been described for different matrices: human whole blood samples (Fonnes et al, 2020); subcutaneous plasma and microdialysate from humans (Dorn et al, 2019); plasma and bile fluid from humans (Yoon et al, 2020); muscle tissue, plasma, and microdialysate from humans (Karjagin et al, 2004); rat plasma (Sampaio et al, 2019); and blood, brain, and biliary microdialysate from rats (Tsai & Chen, 2003), in addition to human feces (Jeffery et al, 2017). However, there are no reports of the analytical method using HPLC to determine MTZ in peritoneal microdialysate and compare it with blood microdialysate from rats.…”