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

Olaf Burkhardt, Martin Brunner, Stephan Schmidt, Maria Grant, Yufei Tang, Hartmut Derendorf

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

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 (Cmax) of 103.3 ± 26.3 mg/L, a terminal elimination half-life (t 1/2) of 3.8 ± 0.6 h and an AUC0-∞ 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 (Cmax = 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%). AUC0-∞ 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.

Original languageEnglish (US)
Pages (from-to)632-636
Number of pages5
JournalJournal of Antimicrobial Chemotherapy
Volume58
Issue number3
DOIs
StatePublished - Sep 2006
Externally publishedYes

Fingerprint

Subcutaneous Fat
Microdialysis
Healthy Volunteers
Skeletal Muscle
Skin
Extracellular Fluid
Muscles
Infection
Subcutaneous Tissue
Tissue Distribution
ertapenem
Protein Binding
Half-Life
Adipose Tissue
Blood Proteins
Volunteers
Proteins
Therapeutics
Pharmaceutical Preparations

Keywords

  • Distribution
  • Pharmacokinetics
  • Subcutis
  • Target site

ASJC Scopus subject areas

  • Pharmacology
  • Microbiology

Cite this

Penetration of ertapenem into skeletal muscle and subcutaneous adipose tissue in healthy volunteers measured by in vivo microdialysis. / Burkhardt, Olaf; Brunner, Martin; Schmidt, Stephan; Grant, Maria; Tang, Yufei; Derendorf, Hartmut.

In: Journal of Antimicrobial Chemotherapy, Vol. 58, No. 3, 09.2006, p. 632-636.

Research output: Contribution to journalArticle

Burkhardt, Olaf ; Brunner, Martin ; Schmidt, Stephan ; Grant, Maria ; Tang, Yufei ; Derendorf, Hartmut. / Penetration of ertapenem into skeletal muscle and subcutaneous adipose tissue in healthy volunteers measured by in vivo microdialysis. In: Journal of Antimicrobial Chemotherapy. 2006 ; Vol. 58, No. 3. pp. 632-636.
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abstract = "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 (Cmax) of 103.3 ± 26.3 mg/L, a terminal elimination half-life (t 1/2) of 3.8 ± 0.6 h and an AUC0-∞ 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 (Cmax = 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{\%}). AUC0-∞ 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.",
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AU - Brunner, Martin

AU - Schmidt, Stephan

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AU - Tang, Yufei

AU - Derendorf, Hartmut

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