Activation of clindamycin phosphate by human skin.
OBJECTIVE
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.


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.


CONCLUSIONS
Phosphatases within the skin have been shown to convert CP to the more potent form Cly.


CONCLUSIONS
Conversion to Cly is a major determinant of antimicrobial activity in the skin layers following topical application of CP.
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MedPharm, Department of Pharmacy, King's College London, Franklin-Wilkins Building, 150 Stamford Street, London SE1 8WA, UK. marc.brown@kcl.ac.uk
Brown
M B
MB
Martin
G P
GP
Forbes
B
B
D000900:Anti-Bacterial Agents / Q000378:metabolism / Q000494:pharmacology*; D002981:Clindamycin / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D008826:Microbial Sensitivity Tests; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D011425:Propionibacterium acnes / Q000187:drug effects; D012867:Skin / Q000378:metabolism* / Q000382:microbiology; D013211:Staphylococcus aureus / Q000187:drug effects; D013212:Staphylococcus epidermidis / Q000187:drug effects
D000900:Anti-Bacterial Agents; D002981:Clindamycin; D010744:Phosphoric Monoester Hydrolases; C007084:clindamycin phosphate