Thornhill D P
Int J Clin Pharmacol Ther Toxicol. 1986 May;24(5):257-61.
Ordinary and sustained-release lithium carbonate were administered at approximately equivalent daily dosage (1.5 and 1.8 g = 20.2 and 24.3 mmol ordinary and sustained-release respectively) in a crossover fashion to 5 manic patients. Actual and theoretical steady state serum levels of both preparations were determined. The sustained-release preparation gave observed serum levels that differed widely from predicted levels. Despite larger inter and intra-subject variations the serum levels at commencement and end of the sampling period were fairly constant. The results suggest that the wide individual variations in steady state profiles may be a consequence of the effect of normal physiological variables on drug absorption in the patient/sickness/diet combination of this study. Apparent erratic absorption in some patients, especially with the sustained-release preparation, indicates that great caution should be exercised in deciding when to monitor serum levels as a guide to adjusting dose. A justification is presented for morning sampling time as the most appropriate, regardless of the type of formulation used.
将普通碳酸锂和缓释碳酸锂以交叉方式给予5名躁狂患者,每日剂量大致相当(普通碳酸锂1.5克和1.8克,分别相当于20.2和24.3毫摩尔普通碳酸锂和缓释碳酸锂)。测定了两种制剂的实际和理论稳态血清水平。缓释制剂的观察到的血清水平与预测水平有很大差异。尽管个体间和个体内差异较大,但采样期开始和结束时的血清水平相当恒定。结果表明,稳态曲线的个体差异较大可能是本研究中患者/疾病/饮食组合中正常生理变量对药物吸收产生影响的结果。一些患者明显的不规则吸收,尤其是缓释制剂,表明在决定何时监测血清水平以指导调整剂量时应格外谨慎。提出了以早晨采样时间为最合适的理由,无论使用何种制剂类型。