Application of microdialysis to clinical pharmacokinetics in humans*

Müller, Markus; Schmid, Rainer; Georgopoulos, Apostolos P.; Buxbaum, Astrid; Wasicek, Carola; Eichler, Hans‐Georg

doi:10.1016/0009-9236(95)90205-8

Cited by 133 publications

(118 citation statements)

References 20 publications

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“…Microdialysis is a promising in vivo technique for accurately measuring the free, unbound concentrations of various molecules (22,25,37), ensuring continuous determination of concentrations in interstitial space fluid in a defined target tissue (31). This property allows relevant data on both pharmacokinetic profiles and pharmacologically active concentrations of substances to be obtained.…”

Section: Discussionmentioning

confidence: 99%

Penetration of Meropenem into Pneumonic Human Lung Tissue as Measured by In Vivo Microdialysis

Tomaselli

Maier

Matzi

et al. 2004

Antimicrob Agents Chemother

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Until recently, information on antibiotic pharmacokinetic properties in infected human lung tissue was limited. We therefore studied a microdialysis-based approach for measurement of the penetration of meropenem into the extracellular space fluid of human pneumonic lung parenchyma. The lung penetration of meropenem was determined for seven patients with pneumonia and metapneumonic pleural empyema treated by decortication. Intraoperatively, two microdialysis probes were inserted into pneumonic lung tissue and one was inserted into healthy skeletal muscle for reference values.

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Section: Discussionmentioning

confidence: 99%

Penetration of Meropenem into Pneumonic Human Lung Tissue as Measured by In Vivo Microdialysis

Tomaselli

Maier

Matzi

et al. 2004

Antimicrob Agents Chemother

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“…The principles of microdialysis (MD) have been described previously in detail (Muller et al, 1995;Muller, 2002). In brief, MD is based on sampling of analytes from the extracellular space of tissues by means of a semipermeable membrane at the tip of a MD probe.…”

Section: Microdialysismentioning

confidence: 99%

Effects of Olanzapine and Ziprasidone on Glucose Tolerance in Healthy Volunteers

Sacher

Mossaheb

Spindelegger

et al. 2007

Neuropsychopharmacol

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Atypical antipsychotics have been linked to a higher risk for glucose intolerance, and consequentially the development of type 2 diabetes mellitus (DM2). We have therefore set out to investigate the acute effects of oral administration of olanzapine and ziprasidone on whole body insulin sensitivity in healthy subjects. Using the standardized hyperinsulinemic euglycemic clamp technique we compared whole body insulin sensitivity of 29 healthy male volunteers after oral intake of either olanzapine 10 mg/day (n ¼ 14) or ziprasidone 80 mg/day (n ¼ 15) for 10 days. A significant decrease (po0.001) in whole body insulin sensitivity from 5.7 ml/h/kg ( ¼ mean, SM ¼ 0.4 ml/h/kg) at baseline to 4.7 ml/h/kg ( ¼ mean, SM ¼ 0.3 ml/h/kg) after oral intake of olanzapine (10 mg/day) for 10 days was observed. The ziprasidone (80 mg/day) group did not show any significant difference (5.2 ± 0.3 ml/h/kg baseline vs 5.1 ± 0.3 ml/h/kg) after 10 days of oral intake. Our main finding demonstrates that oral administration of olanzapine but not ziprasidone leads to a decrease in whole body insulin sensitivity in response to a hyperinsulinemic euglycemic challenge. Our finding is suggestive that not all atypical antipsychotics cause acute direct effects on glucose disposal and that accurate determination of side effect profile should be performed when choosing an atypical antipsychotic.

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“…One dialysis probe was inserted intratumorally into a suitable cutaneous melanoma metastasis and a second probe was inserted into healthy subcutaneous connective tissue within a 10-15 cm distance to the first microdialysis probe. After the insertion of both microdialysis probes there was a 30 min equilibration period (Muller et al, 1995a); subsequently one 15 min microdialysis sample was taken (baseline level). Thereafter, carboplatin (400 mg m-2) was infused intravenously through a second cannula over a time period of 20 min.…”

Section: Study Protocolmentioning

confidence: 99%

“…Recently, the microdialysis technique, based on diffusion of analytes from the interstitial compartment through a semipermeable membrane, has been described for in vivo measurement of drug concentrations in the extracellular fluid (ECF) space in human tissues (Lonnroth et al, 1991;Stahle et al, 1991;Scheyer et al, 1994;Muller et al, 1995a). The aim of this study was to obtain concentration-time profiles in the ECF of solid tumours of a model anti-cancer drug, carboplatin, and thereby to assess the scope of microdialysis for tumour pharmacokinetic studies in man.…”

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confidence: 99%

Measurement of extracellular fluid carboplatin kinetics in melanoma metastases with microdialysis

Blöchl-Daum

Müller²,

Meisinger³

et al. 1996

Br J Cancer

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Summary Clinical anti-tumour efficacy of anti-cancer drugs is a function of dose intensity, i.e. the concentration -time profile in tumour tissue. Hence, information on drug concentration profiles in tumours is of critical importance but appropriate methods for measurement are lacking. The aim of the present study was to obtain, by microdialysis sampling, concentration -time profiles in a solid tumour (melanoma) of a model anti-cancer drug, carboplatin, and thereby to assess the scope of microdialysis for tumour pharmacokinetic studies in man. Six patients with cutaneous melanoma metastases at the extremities or body trunk, scheduled to receive carboplatin (400 mg m 2 i.v.) were studied. Carboplatin concentrations were monitored in serum, intratumoral and subcutaneous tissue. Calibration of the microdialysis probes was carried out in vitro and in vivo with use of the retrodialysis method. Complete carboplatin concentration vs time profiles in tumour and subcutaneous tissue were obtained. Major pharmacokinetic parameters (maximum concentration, time to maximum concentration, area under the curve, elimination half-life) were calculated for tissues and tumour/ serum concentration ratios for carboplatin were derived. Mean free concentrations of carboplatin in cutaneous melanoma metastases reached only about 50-60% of total serum levels; maximal intratumoral concentrations were 7.6 (±2.0; s.e.m.) Mg ml-', mean concentrations in subcutaneous tissue were similar to those in tumour.The present study demonstrates that microdialysis is a novel tool for measuring drug concentrations in solid tumours in humans in vivo and appears to be a valuable addition for pharmacokinetic/pharmacodynamic studies in oncology.

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Application of microdialysis to clinical pharmacokinetics in humans*

Cited by 133 publications

References 20 publications

Penetration of Meropenem into Pneumonic Human Lung Tissue as Measured by In Vivo Microdialysis

Penetration of Meropenem into Pneumonic Human Lung Tissue as Measured by In Vivo Microdialysis

Effects of Olanzapine and Ziprasidone on Glucose Tolerance in Healthy Volunteers

Measurement of extracellular fluid carboplatin kinetics in melanoma metastases with microdialysis

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