Soft-tissue penetration of ceftobiprole in healthy volunteers determined by in vivo microdialysis

April Barbour, Stephan Schmidt, Sreedharan Nair Sabarinath, Maria Grant, Christoph Seubert, Donna Skee, Bindu Murthy, Hartmut Derendorf

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Ceftobiprole is a promising new broad-spectrum cephalosporin with activity against several multidrug-resistant gram-positive and gram-negative species, including methicillin-resistant Staphylococcus aureus. In order to make efficacy predications against these resistant bacteria in soft-tissue infections, i.e., skin and skin structure infections, ceftobiprole's ability to reach the site of action should be explored. Therefore, a microdialysis study was conducted in 12 healthy volunteers to determine the penetration of ceftobiprole into skeletal muscle and subcutaneous (s.c.) adipose tissue after a single intravenous dose of 500 mg. Plasma and tissue interstitial space fluid (ISF) drug concentrations were measured for 24 h from the start of the 2-h intravenous infusion. Pharmacokinetic parameters were determined using noncompartmental analysis. The penetration of ceftobiprole into the ISF of tissues was assessed by comparing the ratios between tissue and plasma of the free drug area under the concentration-time curve (fAUC). It was found that ceftobiprole distributes into the muscle (fAUCmuscle/fAUCplasma of 0.69 ± 0.13) and s.c. adipose tissue (fAUCs.c.adipose/fAUCplasma of 0.49 ± 0.28). The concentrations in both skeletal muscle and s.c. adipose tissue met the efficacy breakpoint (percentage of the time that free drug concentrations remained above the MIC) for at least 40% of the 8-h dosing interval for organisms with a MIC of 2 mg/liter. Therefore, ceftobiprole qualifies as a potential agent with drug penetration capabilities to treat complicated skin and skin structure infections due to both gram-negative and gram-positive pathogens with MICs equal to or below 2 mg/liter.

Original languageEnglish (US)
Pages (from-to)2773-2776
Number of pages4
JournalAntimicrobial Agents and Chemotherapy
Volume53
Issue number7
DOIs
StatePublished - Jul 2009
Externally publishedYes

Fingerprint

Microdialysis
Healthy Volunteers
Subcutaneous Fat
Skin
Extracellular Fluid
Pharmaceutical Preparations
Skeletal Muscle
Soft Tissue Infections
Cephalosporins
Methicillin-Resistant Staphylococcus aureus
Infection
Intravenous Infusions
ceftobiprole
Pharmacokinetics
Bacteria
Muscles

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology
  • Infectious Diseases

Cite this

Barbour, A., Schmidt, S., Sabarinath, S. N., Grant, M., Seubert, C., Skee, D., ... Derendorf, H. (2009). Soft-tissue penetration of ceftobiprole in healthy volunteers determined by in vivo microdialysis. Antimicrobial Agents and Chemotherapy, 53(7), 2773-2776. https://doi.org/10.1128/AAC.01409-08

Soft-tissue penetration of ceftobiprole in healthy volunteers determined by in vivo microdialysis. / Barbour, April; Schmidt, Stephan; Sabarinath, Sreedharan Nair; Grant, Maria; Seubert, Christoph; Skee, Donna; Murthy, Bindu; Derendorf, Hartmut.

In: Antimicrobial Agents and Chemotherapy, Vol. 53, No. 7, 07.2009, p. 2773-2776.

Research output: Contribution to journalArticle

Barbour, A, Schmidt, S, Sabarinath, SN, Grant, M, Seubert, C, Skee, D, Murthy, B & Derendorf, H 2009, 'Soft-tissue penetration of ceftobiprole in healthy volunteers determined by in vivo microdialysis', Antimicrobial Agents and Chemotherapy, vol. 53, no. 7, pp. 2773-2776. https://doi.org/10.1128/AAC.01409-08
Barbour, April ; Schmidt, Stephan ; Sabarinath, Sreedharan Nair ; Grant, Maria ; Seubert, Christoph ; Skee, Donna ; Murthy, Bindu ; Derendorf, Hartmut. / Soft-tissue penetration of ceftobiprole in healthy volunteers determined by in vivo microdialysis. In: Antimicrobial Agents and Chemotherapy. 2009 ; Vol. 53, No. 7. pp. 2773-2776.
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