Direct assessment of peripheral pharmacokinetics in humans:: comparison between cantharides blister fluid sampling, in vivo microdialysis and saliva sampling
Direct assessment of peripheral pharmacokinetics in humans:: comparison between cantharides blister fluid sampling, in vivo microdialysis and saliva sampling
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DOI：
10.1046/j.1365-2125.1998.00805.x
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发表时间：
1998-11-01
影响因子：
3.4
通讯作者：
Müller, M
中科院分区：
文献类型：
--
作者：
Brunner, M;Schmiedberger, A;Müller, M
目的皮肤水疱液采样、体内微透析和唾液采样通常用作测量外周隔室中药物浓度的替代物。虽然预期会显示出可比的结果，但从这些技术中获得的数据从未进行过直接比较。因此，本研究的目的是评估这些techniques.Methods的可比性，扑热息痛，低蛋白结合的模型药物，给7名健康志愿者口服剂量为2000 mg。随后，在阿糖胞苷诱导的皮肤水疱、皮下和骨骼肌组织和唾液的微透析液中同时测量组织动力学，并与血清浓度进行比较。（AUC（泡罩）/AUC（血清））为0.88（95% CI，0.50-1.26），平均比值（AUC（肌肉）/AUC（血清））为1.08（0.67-1.49），平均比值（AUC（皮下）/AUC（血清））为0.96（0.41-1.51），平均比值（AUC（唾液）/AUC（血清））为1.83（1.39-2.27）。在本研究中，三种方法单次经口给药后的浓度曲线不同。浓度（外周）（隔室）/浓度（血清）比的时间过程表明，依地奈德泡罩和微透析液浓度与血清水平密切相关。对于泡罩测量，必须考虑小于2 h的平衡期。相反，唾液浓度显着高于相应的血清concentration.Conclusions皮肤水疱采样和微透析密切反映相应的血清浓度，因此，被证明是合适的技术，用于评估外周室药代动力学。相反，唾液数据高估了相应的血清浓度。
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.