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Activation of clindamycin phosphate by human skin
1MedPharm, Department of Pharmacy, King's College London, Franklin-Wilkins Building, 150 Stamford Street, London SE1 8WA, UK. marc.brown@kcl.ac.uk
Aims:
To investigate the relative antimicrobial activity of clindamycin phosphate (CP) and clindamycin (Cly) and to examine the effect of skin homogenates on the activity of CP.
Methods And Results:
Minimum inhibitory concentrations (MIC) were determined against dermally relevant organisms and bactericidal activity was studied using time-kill methodology. The effect of skin homogenates on the antimicrobial activity of CP was studied by well-diffusion assay. The MIC of Cly was substantially lower than that of CP in all susceptible organisms. Clindamycin also showed greater bactericidal activity (rate of kill) than CP. Phosphatases in skin homogenates activated CP at pH 4-8 with a maximal activation at pH 4.
Conclusion:
Phosphatases within the skin have been shown to convert CP to the more potent form Cly.
Significance And Impact Of The Study:
Conversion to Cly is a major determinant of antimicrobial activity in the skin layers following topical application of CP.