PROTEIN-BINDING AND DISPOSITION OF LIGNOCAINE IN THE ELDERLY
PROTEIN-BINDING AND DISPOSITION OF LIGNOCAINE IN THE ELDERLY
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DOI：
10.1007/bf00544089
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发表时间：
1985-01-01
影响因子：
2.9
通讯作者：
KELLY, JG
中科院分区：
文献类型：
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作者：
CUSACK, B;OMALLEY, K;KELLY, JG
在6名年轻和6名老年非吸烟者中进行了单剂量研究，使用木质素作为具有高内在清除率的模型药物。受试者以随机顺序接受250 mg口服和50 mg静脉注射，并在给药后8小时内测量血液和血浆中的药物浓度。蛋白质结合估计为37 ℃。C平衡透析法。还计算了静脉注射0.15 mg/kg后各个体的吲哚菁绿色动力学。老年人对木质素的生物利用度较高，但吸收率无明显差异。老年人内源性清除率较低。老年人的消除半衰期较长，但在表观分布容积或全身清除率方面无显著差异。吲哚菁绿色的血浆清除率与全身木质素清除率无相关性，老年受试者的血浆清除率较低。两组的血液/血浆木质素比值均小于1。木质素与血浆蛋白的结合表现出浓度依赖性，并且在老年组中更高。最大结合能力的木质素是更大的老年人，但结合亲和力并没有显着变化，随着年龄的增长。更大的口服生物利用度的药物，如木质素可能会产生更高的血浆浓度在老年人。与碘菁绿色不同，在这组非吸烟者中，木质素的全身清除率不受年龄的影响。与许多其他碱性药物一样，木质素的蛋白结合在老年受试者中增加。
Single dose studies were performed in six young and six elderly nonsmokers using lignocaine as a model drug with high intrinsic clearance. Subjects received lignocaine 250 mg orally and 50 mg intravenously in random order and drug concentrations in blood and plasma were measured for up to 8 h after dose. Protein binding was estimated at 37.degree. C by equilibrium dialysis. Indocyanine green kinetics were also calculated in each individual following 0.15 mg/kg intravenously. Bioavailability of lignocaine was greater in the elderly but there was no apparent differnce in the rate of absorption. Intrinsic clearance of lignocaine was lower in the aged. Elimination half-life was longer in the elderly but there was no signifciant difference in apparent volume of distribution or systemic clearance of lignocaine. Plasma clearance of indocyanine green showed no correlation with systemic lignocaine clearance and was lower in the aged subjects. Blood/plasma lignocaine ratio was less than unity in both groups. Binding of lignocaine to plasma proteins showed concentration-dependence and was higher in the geriatric group. Maximum binding capacity of lignocaine was greater in the elderly but the binding affinity did not significantly change with age. Greater oral bioavailability of drugs like lignocaine may produce higher plasma concentrations in the elderly. Unlike idocyanine green, the systemic clearance of lignocaine was unaltered by age in this group of non-smokers. The protein-binding of lignocaine, like many other basic drugs, is increased in elderly subjects.