School of Pharmacy, University of Otago, Dunedin, New Zealand.
Clin Toxicol (Phila). 2011 Aug;49(7):643-7. doi: 10.3109/15563650.2011.604034. Epub 2011 Aug 19.
Current treatment of paracetamol (acetaminophen) poisoning involves initiating a 3-phase N-acetylcysteine (NAC) infusion after comparing a plasma concentration, taken ≥ 4 h post-overdose, to a nomogram. This may result in dosing errors, a delay in treatment, or possibly more adverse effects - due to the use of a high dose rate for the first infusion when treatment is initiated.
Our aim was to investigate a novel dosing regimen for the immediate administration of NAC on admission at a lower infusion rate.
We used a published population pharmacokinetic model of NAC to simulate a scenario where a patient presents to the hospital 2 h post-overdose. The conventional regimen is commenced 6 h post-overdose when the 4-h plasma paracetamol concentration is available. We investigated an NAC infusion using a lower dosing rate initiated immediately on presentation. We determined a dosing rate that gave an area under the curve (AUC) of the concentration-time curve that was the same or greater than that from the conventional regimen on 90% of occasions.
Lower dosing rates of NAC initiated immediately resulted in a similar exposure to NAC. An infusion of 110 mg/kg over the first 5 h (22 mg/kg/h) followed by the last two phases of the conventional regimen, or 200 mg/kg over 9 h (22.6 mg/kg/h) followed by the last phase of the conventional regimen could be used.
The novel dosing regimen allowed immediate treatment of a patient using a lower dosing rate. This greatly simplifies the current dosing regimen and may reduce NAC adverse effects while ensuring the same amount of NAC is delivered.
目前，对乙酰氨基酚（扑热息痛）中毒的治疗方法是在比较中毒后 4 小时以上的血浆浓度与诺模图后，开始进行 3 期 N-乙酰半胱氨酸（NAC）输注。这可能导致给药错误、治疗延迟，或者可能出现更多不良反应 - 因为在开始治疗时，第一输注期使用高剂量率。
我们的目的是研究一种新的给药方案，即在较低输注率的情况下入院时立即给予 NAC。
我们使用已发表的 NAC 群体药代动力学模型来模拟患者在中毒后 2 小时就诊的情况。当获得 4 小时的血浆对乙酰氨基酚浓度时，开始进行常规方案。我们研究了一种在入院时立即开始使用较低剂量率的 NAC 输注。我们确定了一种给药率，使浓度时间曲线下面积（AUC）与常规方案相同或更大，在 90%的情况下。
立即开始的较低 NAC 剂量率导致 NAC 暴露相似。在前 5 小时内输注 110 mg/kg（22 mg/kg/h），然后输注常规方案的最后两个阶段，或者在 9 小时内输注 200 mg/kg（22.6 mg/kg/h），然后输注常规方案的最后一个阶段。
新的给药方案允许使用较低的剂量率立即治疗患者。这大大简化了当前的给药方案，并可能减少 NAC 的不良反应，同时确保给予相同量的 NAC。
