Comparison of three different experimental methods for the assessment of peripheral compartment pharmacokinetics in humans

Müller, Markus; Brunner, Martin; Schmid, Rainer; Putz, Eva Maria; Schmiedberger, Arno; Wallner, Inge; Eichler, Hans Georg

doi:10.1016/s0024-3205(98)00071-x

Cited by 38 publications

(33 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…As shown previously (17), tissue homogenization may lead to relative dilution of the compartment of interest, i.e., the fluid of the interstitial space, and therefore to underestimation of the concentrations in interstitial fluid. Our present findings, however, which demonstrated the strong ability of fosfomycin to penetrate tissues, are in accordance with data obtained previously with animal models with implanted tissue cages (13) and skin blister data (12), although these were shown to poorly reflect the pharmacokinetics in the fluid of the interstitial spaces of target tissues (19).…”

Section: Discussionsupporting

confidence: 93%

Distribution and Antimicrobial Activity of Fosfomycin in the Interstitial Fluid of Human Soft Tissues

Frossard

Joukhadar

Erovic

et al. 2000

Antimicrob Agents Chemother

View full text Add to dashboard Cite

Fosfomycin is a broad-spectrum antibiotic which is established as therapy for uncomplicated lower urinary tract infections. In addition, preliminary data indicate that fosfomycin has a potential role in the treatment of soft tissue infections. However, the use of fosfomycin has not been established for this condition, and it is unclear whether the level of fosfomycin penetration into human soft tissues is high enough to eradicate relevant pathogens. To better characterize the antibiotic potential of fosfomycin, we applied a combined in vivo pharmacokinetic-in vitro pharmacodynamic model to human volunteers. In corresponding in vitro simulation experiments with selected isolates of Staphylococcus aureus, Enterobacter cloacae, and Serratia marcescens for which MICs were 16 g/ml, organisms were undetectable after a single dosing interval. Fosfomycin exhibits a strong ability to penetrate into the fluid of the interstitial space of soft tissues and reaches levels sufficient to substantially inhibit the growth of relevant bacteria at the target site. We therefore conclude that fosfomycin might qualify as an alternative candidate for the therapy of soft tissue infections.

show abstract

Section: Discussionsupporting

confidence: 93%

Distribution and Antimicrobial Activity of Fosfomycin in the Interstitial Fluid of Human Soft Tissues

Frossard

Joukhadar

Erovic

et al. 2000

Antimicrob Agents Chemother

View full text Add to dashboard Cite

show abstract

“…Therefore, there are many available data on the penetration of various antibiotics into cantharis-or suction-induced skin blister fluid (9,17,19,23,30,60,71,111,137,138,146 ). These studies were justified by the notion that "skin blister fluid levels are closer to the biophase than blood" (138).…”

Section: Methods For Studies Of Target Site Drug Distribution In Antimentioning

confidence: 99%

“…The primary focus of SPECT was not the field of anti-infective drug evaluation but cancer research, and it is also used for staging, for diagnostic purposes (such as fever of unknown origin or otitis externa), and for local blood flow measurements (26,182). In vivo SPECT studies enabled quantitative measurements of the tissue PK of 57 Co-or 111 In-labeled bleomycin and 195m Pt-cisplatin in humans (61,77) and indicated that there is marked variability in drug delivery to given tissues. In the field of antibiotic evaluation, SPECT was used to evaluate the penetration of 99m Tc-labeled ciprofloxacin into inflammatory lesions (156).…”

Section: Methods For Studies Of Target Site Drug Distribution In Antimentioning

confidence: 99%

Issues in Pharmacokinetics and Pharmacodynamics of Anti-Infective Agents: Distribution in Tissue

Müller

Peña

Derendorf

2004

Antimicrob Agents Chemother

240

201

View full text Add to dashboard Cite

“…Cantharis-induced skin blisters are caused by a toxic reaction that leads to the formation of a subepidermally located blister. Cantharis-impregnated plasters were used to induce skin blisters as described previously (13). An ointment containing 0.25% cantharidin was prepared by mixing pure cantharidin with ointment base.…”

Section: Methodsmentioning

confidence: 99%

Target Site Concentrations of Ciprofloxacin after Single Intravenous and Oral Doses

Brunner¹,

Staβ

Möller

et al. 2002

Antimicrob Agents Chemother

Self Cite

View full text Add to dashboard Cite

To characterize the potential of ciprofloxacin penetration into human soft tissues following intravenous (i.v.) and oral (p.o.) administration, we measured the free ciprofloxacin concentrations in interstitial space fluid of skeletal muscle and subcutaneous adipose tissue by microdialysis. In addition, ciprofloxacin concentrations were measured in cantharis-induced skin blisters, saliva, and capillary plasma and were compared to the total concentrations in venous plasma. The concentrations in saliva and capillary blood were similar to the corresponding total levels in plasma. In vitro both in vivo ciprofloxacin concentration-time profiles were equally effective against select bacterial strains. In conclusion, single-dose administration of two bioequivalent dosage forms of ciprofloxacin might lead to differences in target site pharmacokinetics. These differences, however, are not related to a difference in target site pharmacodynamics.

show abstract

Comparison of three different experimental methods for the assessment of peripheral compartment pharmacokinetics in humans

Cited by 38 publications

References 15 publications

Distribution and Antimicrobial Activity of Fosfomycin in the Interstitial Fluid of Human Soft Tissues

Distribution and Antimicrobial Activity of Fosfomycin in the Interstitial Fluid of Human Soft Tissues

Issues in Pharmacokinetics and Pharmacodynamics of Anti-Infective Agents: Distribution in Tissue

Target Site Concentrations of Ciprofloxacin after Single Intravenous and Oral Doses

Contact Info

Product

Resources

About