Pharmacokinetics and skin-tissue penetration of XXXX in @entity35 .

@entity35 @entity1 @entity8450 @entity13757
BACKGROUND: @entity13757 is recommended for complicated skin and skin-structure infections. However, information on the penetration of @entity13757 into skin is limited. Therefore, the aim of this in vivo investigation was to determine the pharmacokinetics and skin penetration of @entity13757 in @entity35 . MATERIALS AND METHODS: Concentrations of @entity13757 were determined by high-performance liquid chromatography. A noncompartmental pharmacokinetic analysis was conducted to estimate the rate and extent of @entity13757 penetration from the systemic circulation into skin tissue. Since protein binding of @entity13757 in rat serum was 89.3%, the free maximum concentration (Cmax) and free area under the curve from time 0 to infinity (AUC0-   ) for @entity8450 were calculated as follows: fCmax, @entity8450 = (1 - 0.893) * Cmax, @entity8450 , fAUC0-   , @entity8450 = (1 - 0.893) * AUC0-   , @entity8450 . RESULTS: The following values (mean    standard deviation) were obtained: 0.06  0 L/h/kg for total clearance (CLtotal), 0.44  0.06 hours for elimination-rate constant, 1.58  0.23 hours for half-life, 0.14  0.02 L/kg for steady-state volume distribution, and 2.28  0.33 hours for mean residence time. Time to Cmax was 3.0 hours for @entity8450 and skin tissue. Cmax and AUC0-    for @entity8450 were 175.8  5.1  g/mL and 811.8  31.9  g * h/mL, respectively. Cmax and AUC0-    for skin tissue were 19.1  1.7  g/mL and 113.9  21.8  g * h/mL, respectively. Furthermore, fCmax and fAUC0-    for @entity8450 were 18.8  g/mL and 86.9  g * h/mL, respectively. The degrees of skin-tissue penetration, defined as the Cmax, skin tissue/fCmax, @entity8450 ratio and AUC0-   , skin tissue/fAUC0-   , @entity8450 ratio, were 1.0 and 1.3, respectively. CONCLUSION: @entity13757 exhibited good penetration into skin tissue, supporting its use for the treatment of complicated skin and skin-structure infections. However, further studies are needed in infected @entity1 in order to investigate the relationship between the antimicrobial efficacy of @entity13757 and its drug concentrations in skin tissues.
