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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Penetration of ertapenem into skeletal muscle and subcutaneous adipose tissue in healthy volunteers measured by in vivo microdialysis.

OBJECTIVES: Ertapenem is FDA approved for the treatment of skin and skin-structure infections (SSSI), but its in vivo penetration into the interstitial space of soft tissues is unknown. The present microdialysis study was conducted to measure free, protein-unbound ertapenem concentrations in muscle and subcutaneous tissue. Volunteers and methods: In a single-centre, prospective, open-label study six healthy volunteers (three females, 22-37 years) were treated with 1 g ertapenem given as a single intravenous dose. Microdialysis and plasma samples were collected before and at different time points up to 12 h after medication. Drug concentrations were determined by a validated LC-MS-MS method. RESULTS: No serious or microdialysis-associated adverse events were observed. Ertapenem concentrations in plasma reached a maximum (C(max)) of 103.3 +/- 26.3 mg/L, a terminal elimination half-life (t(1/2)) of 3.8 +/- 0.6 h and an AUC(0-infinity) of 359.7 +/- 66.5 mg.h/L. Mean peak concentrations of free, protein-unbound ertapenem in interstitial space fluid of skeletal muscle and subcutaneous adipose tissue were much lower (C(max) = 6.7 +/- 4.1 and 4.0 +/- 1.6 mg/L, respectively). This degree of tissue distribution is consistent with high concentration-dependent plasma protein binding of ertapenem (84-96%). AUC(0-infinity) values for both muscle and adipose tissue were lower as well (39.7 +/- 24.8 and 18.6 +/- 4.6 mg.h/L). However, unbound interstitial fluid concentrations exceeded MIC(90) values for the important SSSI pathogens for 7 (subcutis) and 10 h (muscle) after dosing. CONCLUSIONS: These results support the previously observed clinical efficacy of ertapenem in the treatment of SSSI.[1]


  1. Penetration of ertapenem into skeletal muscle and subcutaneous adipose tissue in healthy volunteers measured by in vivo microdialysis. Burkhardt, O., Brunner, M., Schmidt, S., Grant, M., Tang, Y., Derendorf, H. J. Antimicrob. Chemother. (2006) [Pubmed]
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