CEFADROXIL, CEFACLOR, CEFUROXIME - INTERSTITIAL FLUID CONCENTRATIONS DETERMINED THROUGH A SKIN WINDOW

The complex interaction between plasma and tissue concentrations of dr ug has significant implications for therapies that use beta-lactam ant ibiotics. This comparative, triple-crossover, open-label study enrolle d 12 healthy adult male volunteers to determine interstitial fluid con centrations of cefadroxil, cefaclor, and cefuroxime. Each participant, by random assignment, received therapeutically equivalent (in skin an d skin-structure infections) single oral doses of cefadroxil 500 mg, c efaclor 250 mg, and cefuroxime axetil 250 mg on separate occasions 1 w eek apart. Serum and interstitial fluid (by skin-window technique) con centrations were assayed sequentially to determine persistence and mag nitude of antibiotic penetration into interstitial fluid. Statisticall y higher concentrations of cefadroxil (5.5 mug/mL) than of cefaclor (1 .2 mug/mL) and cefuroxime (1.1 mug/mL) were documented in interstitial fluid. Cefadroxil (0.63) also demonstrated a tissue fluid:blood area under the curve ratio significantly greater than that achieved by cefa clor (0.48) and comparable to that of cefuroxime axetil (0.60). No sig nificant adverse events occurred with any study medication. The distri bution to interstitial fluids and reliable tissue penetration are fund amental principles of successful antibacterial therapy of skin and ski n-structure infections. The excellent tissue and interstitial fluid pe netration of cefadroxil may contribute to its high degree of efficacy when administered once daily.