scholarly journals In Vivo Microdialysis Study of the Penetration of Daptomycin into Soft Tissues in Diabetic versus Healthy Volunteers

2008 ◽  
Vol 52 (11) ◽  
pp. 3941-3946 ◽  
Author(s):  
Aryun Kim ◽  
Larry A. Suecof ◽  
Christina A. Sutherland ◽  
Lihong Gao ◽  
Joseph L. Kuti ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Healthy Volunteers ◽  
Healthy Subjects ◽  
Soft Tissues ◽  
In Vivo Microdialysis ◽  
Free Drug ◽  
Target Tissue ◽  
Drug Concentrations ◽  
Complicated Skin

ABSTRACT Daptomycin is approved for the treatment of complicated skin and soft tissue infections, including diabetic wounds of the lower extremities, at a dose of 4 mg/kg of body weight once daily. For such localized tissue infections, drug concentrations in the interstitial space are an important determinant of successful therapy. In the diabetic population, peripheral arterial disease may limit antibiotic penetration into the target tissue. The objective of this study was to describe and compare the pharmacokinetic profiles of daptomycin in the interstitial fluid of soft tissues in diabetic and healthy volunteers by using in vivo microdialysis. Twelve subjects (six diabetic and six healthy) received a single 4-mg/kg dose of daptomycin intravenously. Samples of plasma and tissue were simultaneously collected over 24 h. Diabetic and healthy groups were matched in mean age (±10 years), gender ratio, mean weight (±10 kg), and creatinine clearance rate (±20 ml/min/1.73 m2). Pharmacokinetic parameters for plasma were similar between groups (P > 0.05). The mean peak drug concentrations ± standard deviations in tissue were 4.3 ± 3.3 μg/ml and 3.8 ± 1.4 μg/ml for diabetic and healthy subjects, respectively. The degree of tissue penetration, defined as the ratio of the area under the free drug concentration-time curve for tissue to that for plasma, was 0.93 ± 0.61 for diabetic subjects and 0.74 ± 0.09 for healthy subjects (P = 0.46). Daptomycin at 4 mg/kg penetrated well into the soft tissue, reaching concentrations approximately 70 to 90% of those of the free drug in plasma. Moreover, these free, bioactive concentrations in tissue exceeded the MICs for staphylococci and streptococci over the 24-h dosing interval.

scholarly journals Single- and Repeated-Dose Pharmacokinetics of Ceftaroline in Plasma and Soft Tissues of Healthy Volunteers for Two Different Dosing Regimens of Ceftaroline Fosamil

2016 ◽  
Vol 60 (6) ◽  
pp. 3617-3625 ◽  
Author(s):  
Peter Matzneller ◽  
Edith Lackner ◽  
Heimo Lagler ◽  
Beatrix Wulkersdorfer ◽  
Zoe Österreicher ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Healthy Volunteers ◽  
Soft Tissues ◽  
Free Drug ◽  
Phase Iii ◽  
Ceftaroline Fosamil ◽  
Dosing Interval ◽  
Drug Concentrations ◽  
Complicated Skin ◽  
Dosing Regimens

Ceftaroline fosamil (CPT-F) is currently approved for use for the treatment of complicated skin and soft tissue infections and community-acquired pneumonia at 600 mg twice daily (q12h), but other dosing regimens are under evaluation. To date, very limited data on the soft tissue pharmacokinetics (PK) of the active compound, ceftaroline (CPT), are available. CPT concentrations in the plasma, muscle, and subcutis of 12 male healthy volunteers were measured by microdialysis after single and repeated intravenous administration of 600 mg CPT-F q12h or three times daily (q8h) in two groups of 6 subjects each. Relevant PK and PK/pharmacodynamic (PD) parameters were calculated and compared between groups. In plasma, the area under the concentration-time curve (AUC) from 0 to 24 h for total CPT and the cumulative percentage of the dosing interval during which the free drug concentrations exceeded the MIC (fTMIC) for unbound CPT for the currently established threshold of 1 mg/liter were significantly higher in the group receiving CPT-F q8h. Exposure to free drug in soft tissues was higher in the group receiving CPT-F q8h, but high interindividual variability in relevant PK parameters was observed. The mean ratios of the AUC from time zero to the end of the dosing interval (AUC0-τ) for free CPT in soft tissues and the AUC0-τfor the calculated free fraction in plasma at steady state ranged from 0.66 to 0.75. Administration of CPT-F q8h led to higher levels of drug exposure in all investigated compartments. When MIC values above 1 mg/liter were assumed, the calculatedfTMICafter dosing q12h was markedly lower than that after dosing q8h. The clinical implications of these differences are discussed in light of recently completed clinical phase III and PK/PD studies.

scholarly journals Single-dose pharmacokinetics of temocillin in plasma and soft tissues of healthy volunteers after intravenous and subcutaneous administration: a randomized crossover microdialysis trial

2020 ◽  
Vol 75 (9) ◽  
pp. 2650-2656 ◽  
Author(s):  
Peter Matzneller ◽  
Perrin Ngougni Pokem ◽  
Arnaud Capron ◽  
Edith Lackner ◽  
Beatrix Wulkersdorfer ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Protein Binding ◽  
Healthy Volunteers ◽  
Plasma Protein Binding ◽  
Plasma Protein ◽  
Soft Tissues ◽  
Therapeutic Option ◽  
Subcutaneous Administration ◽  
Intravenous Route ◽  
Drug Concentrations

Abstract Background The antibiotic temocillin has recently been rediscovered as a promising therapeutic option against MDR Gram-negative bacteria. However, some aspects of the pharmacokinetic (PK) profile of the drug are still to be elucidated: subcutaneous administration of temocillin might be of interest as an alternative to the intravenous route in selected patients. Similarly, information on the penetration of temocillin into human soft tissues is lacking. Objectives To investigate the feasibility and plasma PK of subcutaneous dosing as well as soft tissue PK of temocillin after intravenous administration to healthy volunteers. Methods Eight healthy volunteers received 2 g of temocillin both as intravenous and subcutaneous infusion in a randomized two-period crossover study. Concentration–time profiles of total temocillin in plasma (after both routes) and of unbound temocillin in plasma, muscle and subcutis (only after intravenous dosing) were determined up to 12 h post-dose. Results Subcutaneous dosing caused some infusion site discomfort but resulted in sustained drug concentrations over time with only slightly decreased overall exposure compared with intravenous dosing. Plasma protein binding of temocillin showed concentration-dependent behaviour and was higher than previously reported. Still, unbound drug concentrations in muscle and subcutis determined by microdialysis markedly exceeded those in plasma, suggesting good tissue penetration of temocillin. Conclusions The subcutaneous administration of temocillin is a valid and feasible alternative to intravenous dosing. With the description of plasma protein binding and soft tissue PK of temocillin in healthy volunteers, this study provides important information that adds to the ongoing characterization of the PK profile of temocillin and might serve as input for PK/PD considerations.

scholarly journals Penetration of Linezolid into Soft Tissues of Healthy Volunteers after Single and Multiple Doses

2005 ◽  
Vol 49 (6) ◽  
pp. 2367-2371 ◽  
Author(s):  
Pejman Dehghanyar ◽  
Cornelia Bürger ◽  
Markus Zeitlinger ◽  
Florian Islinger ◽  
Florian Kovar ◽  
...  
Keyword(s):  
Healthy Volunteers ◽  
Soft Tissues ◽  
In Vivo Microdialysis ◽  
Time Curve ◽  
Concentration Time ◽  
Multiple Doses ◽  
Muscle Tissues ◽  
Subcutaneous Adipose ◽  
Free Plasma

ABSTRACT The present study tested the ability of linezolid to penetrate soft tissues in healthy volunteers. Ten healthy volunteers were subjected to linezolid drug intake at a dose of 600 mg twice a day for 3 to 5 days. The first dose was administered intravenously. All following doses were self-administered orally. The tissue penetration of linezolid was assessed by use of in vivo microdialysis. In the single-dose experiments the ratios of the area under the concentration-time curve from 0 to 8 h (AUC0-8) for tissue to the AUC0-8 for free plasma were 1.4 ± 0.3 (mean ± standard deviation) and 1.3 ± 0.4 for subcutaneous adipose and muscle tissue, respectively. After multiple doses, the corresponding mean ratios were 0.9 ± 0.2 and 1.0 ± 0.5, respectively. The ratios of the AUC from 0 to 24 h (AUC0-24) for free linezolid in tissues to the MIC were between 50 and 100 for target pathogens with MICs between 2 and 4 mg/liter. In conclusion, the present study showed that linezolid penetrates rapidly into the interstitial space fluid of subcutaneous adipose and skeletal muscle tissues in healthy volunteers. On the basis of pharmacokinetic-pharmacodynamic calculations, we suggest that linezolid concentrations in soft tissues can be considered sufficient to inhibit the growth of many clinically relevant bacteria.

scholarly journals Concentrations of Gemifloxacin at the Target Site in Healthy Volunteers after a Single Oral Dose

2004 ◽  
Vol 48 (11) ◽  
pp. 4246-4249 ◽  
Author(s):  
Florian Islinger ◽  
Rene Bouw ◽  
Mathias Stahl ◽  
Edith Lackner ◽  
Petra Zeleny ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Soft Tissue ◽  
Oral Dose ◽  
Healthy Volunteers ◽  
Single Oral Dose ◽  
Soft Tissues ◽  
Therapeutic Option ◽  
The Mean

ABSTRACT Free gemifloxacin concentrations in the interstitial space fluid of skeletal muscle and subcutaneous adipose tissue were measured by means of in vivo microdialysis to characterize the ability of gemifloxacin to penetrate human soft tissues. Twelve healthy volunteers received a single oral dose of 320 mg of gemifloxacin. The mean areas under the concentration-time curves from 0 to 10 h (AUC0-10) were significantly higher for soft tissue than for unbound gemifloxacin in plasma (P < 0.05). The ratios of the mean AUC0-10 for tissue to the AUC0-10 for free gemifloxacin in plasma were 1.7 ± 0.7 (mean ± standard deviation) for skeletal muscle and 2.4 ± 1.0 for adipose tissue. The AUC0-24 ratios for free gemifloxacin in tissues to the MIC at which 90% of frequently isolated bacteria are inhibited were close to or higher than 100 h. Therefore, based on pharmacokinetic and pharmacodynamic calculations, we conclude that gemifloxacin might be a useful therapeutic option for the treatment of soft tissue infections.

scholarly journals Penetration of Piperacillin and Tazobactam into Inflamed Soft Tissue of Patients with Diabetic Foot Infection

2005 ◽  
Vol 49 (10) ◽  
pp. 4368-4371 ◽  
Author(s):  
F. J. Legat ◽  
R. Krause ◽  
P. Zenahlik ◽  
C. Hoffmann ◽  
S. Scholz ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Diabetic Foot ◽  
Extracellular Space ◽  
Soft Tissues ◽  
In Vivo Microdialysis ◽  
Diabetic Foot Infection

ABSTRACT We investigated the pharmacokinetics of piperacillin and tazobactam in the extracellular space fluid of inflamed soft tissues of six patients with diabetic foot infection using in vivo microdialysis and found similar penetration for piperacillin but not for tazobactam into inflamed and noninflamed soft tissue.

scholarly journals Soft-Tissue Penetration of Ceftobiprole in Healthy Volunteers Determined by In Vivo Microdialysis

2009 ◽  
Vol 53 (7) ◽  
pp. 2773-2776 ◽  
Author(s):  
April Barbour ◽  
Stephan Schmidt ◽  
Sreedharan Nair Sabarinath ◽  
Maria Grant ◽  
Christoph Seubert ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Soft Tissue ◽  
Healthy Volunteers ◽  
Free Drug ◽  
Resistant Bacteria ◽  
Gram Positive ◽  
Gram Negative ◽  
Skin Structure ◽  
Drug Concentrations

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.

scholarly journals In vivo soft tissue reinforcement with bacterial nanocellulose

2021 ◽  
Author(s):  
Irene Anton-Sales ◽  
Soledad Roig-Sanchez ◽  
Kamelia Anna Traeger ◽  
Christine Weis ◽  
Anna Laromaine ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Soft Tissues ◽  
Hernia Surgery ◽  
Bacterial Nanocellulose ◽  
Surgical Meshes

The use of surgical meshes to reinforce damaged internal soft tissues has been instrumental for successful hernia surgery; a highly prevalent condition affecting yearly more than 20 million patients worldwide....

Reliability Investigation of Tissue Resonator Indenter Device

2010 ◽  
Author(s):  
Ming Jia ◽  
Jean W. Zu ◽  
Alireza Hariri
Keyword(s):  
Mechanical Properties ◽  
Soft Tissue ◽  
Soft Tissues ◽  
Tissue Properties ◽  
University Of Toronto ◽  
In Vivo Measurements ◽  
Disease Diagnostics ◽  
Working Principle ◽  
The University

Knowledge of tissue mechanical properties is widely required by medical applications, such as disease diagnostics, surgery operation, simulation, planning, and training. A new portable device, called Tissue Resonator Indenter Device (TRID), has been developed for measurement of regional viscoelastic properties of soft tissues at the Bio-instrument and Biomechanics Lab of the University of Toronto. As a device for soft tissue properties in-vivo measurements, the reliability of TRID is crucial. This paper presents TRID’s working principle and the experimental study of TRID’s reliability with respect to inter-reliability, intra-reliability, and the indenter misalignment effect as well. The experimental results show that TRID is a reliable device for in-vivo measurements of soft tissue mechanical properties.

Using MR Imaging and X-Ray Fluoroscopy to Quantify the Effects of Soft-Tissue Artifact on Measurement of Knee-Joint Kinematics

2009 ◽  
Author(s):  
Massoud Akbarshahi ◽  
Justin W. Fernandez ◽  
Anthony Schache ◽  
Richard Baker ◽  
Marcus G. Pandy
Keyword(s):  
Soft Tissue ◽  
Knee Joint ◽  
Soft Tissues ◽  
Surgical Techniques ◽  
Joint Kinematics ◽  
Segmental Motion ◽  
Coordinate Systems ◽  
Knee Joint Kinematics ◽  
Soft Tissue Artifact

The ability to accurately measure joint kinematics in vivo is of critical importance to researchers in the field of biomechanics [1]. Applications range from the quantitative evaluation of different surgical techniques, treatment methods and/or implant designs, to the development of computer-based models capable of simulating normal and pathological musculoskeletal conditions [1,2]. Currently, non-invasive marker-based three dimensional (3D) motion analysis is the most commonly used method for quantitative assessment of normal and pathological locomotion. The accuracy of this technique is influenced by movement of the soft tissues relative to the underlying bones, which causes inaccuracies in the determination of segmental anatomical coordinate systems and tracking of segmental motion. The purpose of this study was to quantify the errors in the measurement of knee-joint kinematics due solely to soft-tissue artifact (STA) in healthy subjects. To facilitate valid inter-subject comparisons of the kinematic data, relevant anatomical coordinate systems were defined using 3D bone models generated from magnetic resonance imaging (MRI).

scholarly journals In Vivo Comparison of the Pharmacodynamic Targets for Echinocandin Drugs against Candida Species

2010 ◽  
Vol 54 (6) ◽  
pp. 2497-2506 ◽  
Author(s):  
D. Andes ◽  
D. J. Diekema ◽  
M. A. Pfaller ◽  
J. Bohrmuller ◽  
K. Marchillo ◽  
...  
Keyword(s):  
Candida Glabrata ◽  
Candida Parapsilosis ◽  
Free Drug ◽  
Response Relationship ◽  
Time Curve ◽  
Exposure Response ◽  
Concentration Time ◽  
Drug Concentrations ◽  
Good Descriptor

ABSTRACT Previous pharmacodynamic studies using in vivo candidiasis models have demonstrated that the 24-h area under the concentration-time curve (AUC)/MIC is a good descriptor of the echinocandin exposure-response relationship. Further studies investigating the 24-h AUC/MIC target for a stasis endpoint identified free-drug 24-h AUC/MIC against Candida albicans and were similar for two echinocandins, anidulafungin and micafungin. The current studies expand investigation of a third echinocandin (caspofungin) and compare the pharmacodynamic target among C. albicans, Candida glabrata, and Candida parapsilosis. Treatment studies were conducted with six C. albicans, nine C. glabrata, and 15 C. parapsilosis strains with various MICs (anidulafungin, 0.015 to 4.0 μg/ml; caspofungin, 0.03 to 4.0 μg/ml; and micafungin, 0.008 to 1.0 μg/ml). Efficacy was closely tied to MIC and the 24-h AUC/MIC. Therapy against C. parapsilosis required more of each echinocandin on a mg/kg basis. Caspofungin required less drug on a mg/kg basis for efficacy against all of the organisms than did the other two drugs. However, the 24-h AUC/MIC targets were similar among the echinocandins when free drug concentrations were considered, suggesting the relevance of protein binding. The targets for C. parapsilosis (mean, 7) and C. glabrata (mean, 7) were significantly lower than those for C. albicans (mean, 20) for each echinocandin. The results suggest that current susceptibility breakpoints and the consideration of organism species in these determinations should be reexplored.

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