Start Over

Pharmacokinetics and skin-tissue penetration of daptomycin in rats.

Authors :: Kazuaki Matsumoto
Masashi Kitaoka
Yuko Kuroda
Kazuro Ikawa
Norifumi Morikawa
Junichi Sasaki
Osamu Iketani
Satoshi Iwata
Tetsuya Horino
Seiji Hori
Junko Kizu
Source :: Clinical Pharmacology; 2015, Vol. 7, p79-81, 3p
Publication Year :: 2015
Abstract: Background: Daptomycin is recommended for complicated skin and skin-structure infections. However, information on the penetration of daptomycin into skin is limited. Therefore, the aim of this in vivo investigation was to determine the pharmacokinetics and skin penetration of daptomycin in rats. Materials and methods: Concentrations of daptomycin were determined by high-performance liquid chromatography. A noncompartmental pharmacokinetic analysis was conducted to estimate the rate and extent of daptomycin penetration from the systemic circulation into skin tissue. Since protein binding of daptomycin in rat serum was 89.3%, the free maximum concentration (C<subscript>max</subscript>) and free area under the curve from time 0 to infinity (AUC<subscript>0-∞</subscript>) for plasma were calculated as follows: fC<subscript>max, plasma</subscript> = (1 - 0.893) × C<subscript>max, plasma</subscript>, fAUC<subscript>0-∞, plasma</subscript> = (1 - 0.893) × AUC<subscript>0-∞, plasma</subscript>. Results: The following values (mean ± standard deviation) were obtained: 0.06±0 L/h/kg for total clearance (CL<subscript>total</subscript>), 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 C<subscript>max</subscript> was 3.0 hours for plasma and skin tissue. C<subscript>max</subscript> and AUC<subscript>0-∞</subscript> for plasma were 175.8±5.1 µg/mL and 811.8±31.9 µg × h/mL, respectively. C<subscript>max</subscript> and AUC<subscript>0-∞</subscript> for skin tissue were 19.1±1.7 µg/mL and 113.9±21.8 µg × h/mL, respectively. Furthermore, fC<subscript>max</subscript> and fAUC<subscript>0-∞</subscript> for plasma were 18.8 µg/mL and 86.9 µg × h/mL, respectively. The degrees of skin-tissue penetration, defined as the C<subscript>max, skin tissue</subscript>/fC<subscript>max, plasma</subscript> ratio and AUC<subscript>0-∞</subscript>, skin tissue/fAUC<subscript>0-∞, plasma</subscript> ratio, were 1.0 and 1.3, respectively. Conclusion: Daptomycin 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 patients in order to investigate the relationship between the antimicrobial efficacy of daptomycin and its drug concentrations in skin tissues. [ABSTRACT FROM AUTHOR]