Chan K, Tse J, Jennings F, Orme M L
Methods Find Exp Clin Pharmacol. 1985 May;7(5):245-51.
The kinetics of intravenous pethidine (150 micrograms kg-1) were determined in 10 healthy Caucasian subjects under uncontrolled and controlled (acidic and alkaline) urinary pH. Although large variations in the 48 hr urinary recovery of pethidine and norpethidine (26.9 +/- 5.9% & 23.4 +/- 4.6%, 0.6 +/- 0.3% & 3.6 +/- 1.6%, 6.9 +/- 3.2% & 17.4 +/- 6.6%, respectively, under acidic, alkaline and uncontrolled urinary pH were induced by change in urinary pH, the terminal t1/2 (7-8 hr), the AUC and the plasma concentration-time profiles were not affected. Under all these conditions, the disappearance of pethidine from the plasma was described by a triexponential function. A 3-compartment open model with input into the central compartment and elimination from both the central and the fast accessible (metabolising) compartment was proposed to interpret pethidine distribution in the body. This model explains the complimentary elimination of pethidine by renal excretion and metabolism. Under alkaline urinary pH, the hydrolytic route predominates as recovery of pethidine and norpethidine in the urine is significantly lower under this condition. Acidification of the urine may increase body clearance of the unchanged drug due mainly to greater renal clearance, and this may be useful clinically to treat acute pethidine poisoning and when the complimentary hepatic metabolism is impaired.
在10名健康的白种人受试者中，测定了静脉注射哌替啶（150微克/千克）在尿液pH值未控制以及控制（酸性和碱性）情况下的动力学。尽管尿液pH值的变化导致哌替啶和去甲哌替啶在48小时尿液回收率上有很大差异（酸性、碱性和未控制尿液pH值情况下，回收率分别为26.9±5.9%和23.4±4.6%、0.6±0.3%和3.6±1.6%、6.9±3.2%和17.4±6.6%），但终末半衰期（7 - 8小时）、曲线下面积（AUC）以及血浆浓度 - 时间曲线并未受到影响。在所有这些条件下，血浆中哌替啶的消除可用三指数函数描述。提出了一个三室开放模型，药物输入中央室，从中央室和快速可及（代谢）室消除，以解释哌替啶在体内的分布。该模型解释了哌替啶通过肾排泄和代谢的互补消除。在碱性尿液pH值条件下，水解途径占主导，因为在此条件下尿液中哌替啶和去甲哌替啶的回收率显著降低。尿液酸化可能主要由于更大的肾清除率而增加未变化药物的体内清除率，这在临床上治疗急性哌替啶中毒以及肝脏互补代谢受损时可能有用。
