| Title |
Pharmacokinetics and skin-tissue penetration of daptomycin in rats
|
|---|---|
| Published in |
Clinical Pharmacology : Advances and Applications, May 2015
|
| DOI | 10.2147/cpaa.s83447 |
| Pubmed ID | |
| Authors |
Kazuaki Matsumoto, Masashi Kitaoka, Yuko Kuroda, Kazuro Ikawa, Norifumi Morikawa, Junichi Sasaki, Osamu Iketani, Satoshi Iwata, Tetsuya Horino, Seiji Hori, Junko Kizu |
| Abstract |
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. 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 (Cmax) and free area under the curve from time 0 to infinity (AUC0-∞) for plasma were calculated as follows: fCmax, plasma = (1 - 0.893) × Cmax, plasma, fAUC0-∞, plasma = (1 - 0.893) × AUC0-∞, plasma. 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 plasma and skin tissue. Cmax and AUC0-∞ for plasma were 175.8±5.1 μg/mL and 811.8±31.9 μg × h/mL, respectively. Cmax and AUC0-∞ for skin tissue were 19.1±1.7 μg/mL and 113.9±21.8 μg × h/mL, respectively. Furthermore, fCmax and fAUC0-∞ for plasma were 18.8 μg/mL and 86.9 μg × h/mL, respectively. The degrees of skin-tissue penetration, defined as the Cmax, skin tissue/fCmax, plasma ratio and AUC0-∞, skin tissue/fAUC0-∞, plasma ratio, were 1.0 and 1.3, respectively. 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. |
X Demographics
The data shown below were collected from the profile of 1 X user who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Practitioners (doctors, other healthcare professionals) | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 10 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 10 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Professor | 3 | 30% |
| Student > Bachelor | 2 | 20% |
| Researcher | 2 | 20% |
| Student > Ph. D. Student | 1 | 10% |
| Lecturer > Senior Lecturer | 1 | 10% |
| Other | 0 | 0% |
| Unknown | 1 | 10% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 4 | 40% |
| Pharmacology, Toxicology and Pharmaceutical Science | 1 | 10% |
| Chemical Engineering | 1 | 10% |
| Agricultural and Biological Sciences | 1 | 10% |
| Chemistry | 1 | 10% |
| Other | 0 | 0% |
| Unknown | 2 | 20% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 24 May 2015.
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#20,656,820
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Outputs from Clinical Pharmacology : Advances and Applications
#147
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#206,512
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Outputs of similar age from Clinical Pharmacology : Advances and Applications
#1
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