• 作者： 何善台; 胡幼圃; 鮑力恒; 何維柏; 李世俊
• 作者服務機構： 國防醫學院麻醉學科; 國防醫學院藥學系; 亞東醫院麻醉科; 國防醫學院外科學科
• 中文摘要： Thiopentone 在老年手術病人劑量降低之原因，已經證實不是由於藥效學方面的改變。本研究即針對此一現象以藥動學之原理加以探討其可能之機轉。在13個手術病人（6個21～33歲，7個67～82歲），均給予靜注 Thiopentone 3mg 之劑量。給藥後定時抽取動脈血，以HPLC測定Thiopentone在動脈血漿及血球中之濃度，血漿蛋白結合率等。Thiopentone 動脈血漿濃度可以二室式表示；在老年人之分佈速率常數(α)顯著較年輕人為小（P<0.001），且分佈半衰期也較長（P<0.05），微量分佈速率常數之差，也顯著的減小（P<0.001），另外Thiopentone 血漿蛋白結合率在老年人也顯著的降低了（P<0.05），但是分佈體積在老年人卻未減少。同時，在給予相同劑量下，最初有藥效的1，1.5及2分鐘時，老年人動脈血漿濃度較年輕人顯著為高。綜合上述，我們認為Thiopentone在老年人體內之緩慢分佈，低血漿蛋白結合率以致造成較高的血中濃度是手術時需較低劑量的主要原因。
• 英文摘要： The dose of thiopentone required to induce anesthesia in adults decreasing with age is not due topharmacodynamic change. The change of pharmacokinetic properties of thiopentone with age in under-going surgery patient's arterial blood was investigated in seven elderly (67-82 yr) and six young (21-33 yr)patients of both sexes. Thiopentone (3 mg ) was administered intravenously and arterial blood sampleswere obtained immediately after the injection to measure plasma and red blood cell thiopentone concen-trations by an HPLC method. Plasma protein binding was studied using ultracentrifuge method. The dis-appearance of thiopentone from the arterial blood was described by a two-compartment open model.The distribution rate constant (α) was significantly larger in the young patients (p ＜ 0.001). The dis-tribution half-life was longer in the elderly (p ＜ 0.05). Both the input microscopic rate constant, and the exit microscopic rate constant, with the central compartment were significantly larger in theyoung patients. (p ＜ 0.02 and p ＜ 0.001, respectively). The difference between the exit and input micro-scopic rate constant, was much larger in the young patients (p ＜ 0.001). The plasma proteinbinding was signifcantly reduced in the elderly (p ＜ 0.05). The apparent overall volume of distribution,Vd was not significantly different between young and elder patients. However, the volume of distributionof the central compartment was smaller in the young patients (p ＜ 0.05). This was probably due to thedifficulty of estimation of initial thiopentone plasma concentration post-equilibrium in the central com-partment after administration of thopentone. Also, the initial thiopentone plasma concentrations at 1 min,1.5 min and 2 min were significantly higher in the elderly after the same dose, 3 mg , was given. Fromthe slower distribution, the lower extent of plasma protein binding and the higher arterial plasma levels inthe elderly after a given dose of thiopentone, it is suggested that the slower distribution and lower plasmaprotein binding are predominant in determining the lower dose requirement in the elderly patients.
• 中文關鍵字： Age factor; Thiopentone; Anesthetics; Pharmacokinetics
• 英文關鍵字： --