Application of microdialysis to clinical pharmacokinetics in humans.

OBJECTIVE: Measurement of drug concentrations in tissues would be useful for clinical pharmacokinetic studies, but appropriate experimental methods are not available at present. The aim of this study was to assess the scope and limitations of the microdialysis technique for human tissue pharmacokinetic studies.
METHODS: Microdialysis probes were inserted into the medial vastus muscle or the periumbilical subcutaneous adipose layer of 13 healthy volunteers. Thereafter, volunteers received either acetaminophen (paracetamol, 1000 mg orally) or gentamicin (160 mg, intravenous bolus). Drug concentrations were monitored in plasma, muscle, and subcutaneous tissue. Calibration of the microdialysis probes was carried out in vitro and in vivo with use of the retrodialysis method.
RESULTS: For both model compounds, complete concentration versus time profiles in muscle and subcutaneous tissue could be obtained. Major pharmacokinetic parameters (absorption half-life, elimination half-life, maximum concentration, time to reach maximum concentration, area under the curve, and area under the inhibitory curve) were calculated for tissues; tissue/plasma concentration ratios could be derived. Reproducibility of tissue drug concentration measurements was high.
CONCLUSIONS: We have shown that microdialysis sampling is a suitable tool for measuring drug concentrations in human muscle and subcutaneous tissues. Microdialysis is readily applicable, relatively noninvasive, and reproducible. This technique may become a valuable addition for pharmacokinetic characterization of selected drugs.