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Aims Skin blister fluid sampling, in vivo microdialysis and saliva sampling are commonly employed as surrogates for the measurement of drug concentrations in peripheral compartments. Although expected to exhibit comparable results, data derived from these techniques have never been directly compared. Thus, the aim of the present study was to evaluate the comparability of these techniques. Methods Paracetamol, a model drug with low protein binding, was administered to seven healthy volunteers at an oral dose of 2000 mg. Subsequently, tissue kinetics were measured simultaneously in cantharides induced skin blisters, microdialysates of subcutaneous-and skeletal muscle-tissue and saliva and compared to serum concentrations. Results Mean ratio (AUC blister /AUC serum ) was 0.88 (95% CI, 0.50-1.26), mean ratio (AUC muscle /AUC serum ) was 1.08 (0.67-1.49), mean ratio (AUC subcutaneous /AUC serum ) was 0.96 (0.41-1.51) and mean ratio (AUC saliva /AUC serum ) was 1.83 (1.39-2.27). In this study the concentration profiles after single oral administration differed among the three methods. The time course of the concentration peripheral compartment /concentration serum -ratios showed that cantharides blister and microdialysate concentrations closely paralleled serum levels. An equilibration period of less than 2 h had to be taken into account for blister measurements. In contrast, saliva concentrations were significantly higher than corresponding serum concentrations. Conclusions Skin blister sampling and microdialysis closely mirrored corresponding serum concentrations and, thus, proved to be suitable techniques for the assessment of peripheral compartment pharmacokinetics. In contrast, saliva data overestimated the corresponding serum concentrations.

These results confirm that the Edwards Duromedics valve shows excellent performance concerning thromboembolism, hemolysis, and functional improvement and will serve as a reference for the last version, the Edwards Tekna valve, where comparable long-term data are currently not available.