Katayama K, Tsubota E, Endoh M, Kakemi M, Koizumi T
Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, Japan.
J Pharmacobiodyn. 1990 Mar;13(3):179-85. doi: 10.1248/bpb1978.13.179.
To predict quantitatively drug interaction kinetics from the single-drug clearance studies, we examined the effect of iodopyracet (IOD) on sulfamethizole (SMZ) excretion in rabbits. Even though the decline of systemic IOD plasma concentration was linear, the renal clearance of SMZ decreased significantly in the presence of IOD. The results could be described by a perfusion model incorporated with the competitive inhibition for tubular secretion. For IOD with a high extraction ratio, it was suggested that a heavy load of the drug was supplied to the sites of secretion and caused the saturation of transport systems, even though the renal excretion kinetics were apparently linear in respect to the systemic circulation. These facts indicated that a linear relationship between the concentrations in the systemic circulation and at the sites of tubular secretion can not always be presumed. Consequently, SMZ-IOD interaction study stressed the importance of the drug concentrations at the sites of interaction for quantitative elucidation of drug-drug interactions.
为了从单药清除率研究中定量预测药物相互作用动力学，我们研究了碘吡啦啥（IOD）对家兔磺胺甲噻二唑（SMZ）排泄的影响。尽管全身IOD血浆浓度呈线性下降，但在有IOD存在时，SMZ的肾清除率显著降低。结果可用结合肾小管分泌竞争性抑制的灌注模型来描述。对于具有高提取率的IOD，尽管肾排泄动力学相对于体循环明显呈线性，但提示大量药物被输送到分泌部位并导致转运系统饱和。这些事实表明，不能总是假定体循环和肾小管分泌部位的浓度之间存在线性关系。因此，SMZ - IOD相互作用研究强调了相互作用部位药物浓度对于定量阐明药物 - 药物相互作用的重要性。
