Clinical and Experimental Toxicology Unit, Department of Emergency Medicine, Prince of Wales Hospital, Barker Street, Randwick, New South Wales 2031, Australia.
Emerg Med Australas. 2010 Dec;22(6):548-55. doi: 10.1111/j.1742-6723.2010.01354.x.
Panadol Extend (PEx) is an over-the-counter, modified-release formulation of paracetamol. Each 665 mg tablet contains 69% slow-release and 31% immediate-release paracetamol. In simulated human overdose, PEx exhibits lower and later peak serum concentrations and a lower area-under-the-curve (AUC) than comparable doses of immediate-release paracetamol (APAP-IR). The lower AUC might result from incomplete absorption of paracetamol or simultaneous metabolism with absorption.
Do differences in pharmacokinetics (PK) between PEx and APAP-IR result from incomplete absorption or simultaneous absorption and metabolism of paracetamol?
Cross-over study of 80 mg/kg of PEx or APAP-IR in nine volunteers. Serial plasma paracetamol, glucuronide, sulphate and cysteine metabolite estimates performed over 24 h. Peak plasma concentration (Cmax), AUC((0-∞),) time to peak concentration (Tmax) and elimination half-life (t(1/2) ) were compared.
PEx exhibited significantly lower paracetamol Cmax (252.33 µmol/L vs 565.56 µmol/L, P= 0.0421), AUC((0-∞)) (2133 µmol/h/L vs 2637 µmol/h/L, P= 0.0004) and delayed Tmax (2.889 h vs 1.389 h, P= 0.0189) than APAP-IR. Sulphate metabolite PK parameters for both preparations, PEx vs APAP-IR, showed similar AUC((0-∞)) (1369 µmol/h/L vs 1089 µmol/h/L), Tmax (3.889 h vs 4.444 h), Cmax (95.889 µmol/L vs 95.889 µmol/L) and t(1/2) (3.895 h vs 3.810 h). Glucuronide metabolite concentrations revealed that PEx produced a lower Cmax (257.44 µmol/L vs 335.22 µmol/L, P= 0.0239) than APAP-IR. All other pharmacokinetic parameters were similar. Cysteine metabolite was not detected.
There were minor differences between the PK parameters of the two major paracetamol metabolites of these two preparations in simulated overdose. The variability in paracetamol AUC seen between the two preparations in moderate overdose might be explained by concurrent metabolism of paracetamol during slower absorption with PEx.
扑热息痛延长释放片（PEx）是一种非处方的，控释制剂的对乙酰氨基酚。每片 665 毫克含有 69%的缓释和 31%的速释对乙酰氨基酚。在模拟人体过量的情况下，PEx 表现出较低和较晚的血清浓度峰值和较低的曲线下面积（AUC）比等效剂量的速释对乙酰氨基酚（APAP-IR）。较低的 AUC 可能是由于对乙酰氨基酚吸收不完全或同时与吸收的代谢有关。
PEx 和 APAP-IR 之间的药代动力学（PK）差异是否是由于对乙酰氨基酚吸收不完全或同时吸收和代谢所致？
对 9 名志愿者进行了 80 毫克/千克 PEx 或 APAP-IR 的交叉研究。在 24 小时内连续检测血浆对乙酰氨基酚、葡萄糖醛酸、硫酸盐和半胱氨酸代谢物的浓度。比较了峰值血浆浓度（Cmax）、AUC（0-∞）、达峰时间（Tmax）和半衰期（t1/2）。
与 APAP-IR 相比，PEx 表现出明显较低的对乙酰氨基酚 Cmax（252.33 µmol/L 比 565.56 µmol/L，P=0.0421）、AUC（0-∞）（2133 µmol/h/L 比 2637 µmol/h/L，P=0.0004）和 Tmax 延迟（2.889 小时比 1.389 小时，P=0.0189）。两种制剂的硫酸盐代谢物 PK 参数，PEx 与 APAP-IR 相比，AUC（0-∞）（1369 µmol/h/L 比 1089 µmol/h/L）、Tmax（3.889 小时比 4.444 小时）、Cmax（95.889 µmol/L 比 95.889 µmol/L）和 t1/2（3.895 小时比 3.810 小时）相似。葡萄糖醛酸代谢物浓度表明，PEx 产生的 Cmax（257.44 µmol/L 比 335.22 µmol/L，P=0.0239）低于 APAP-IR。所有其他药代动力学参数均相似。未检测到半胱氨酸代谢物。
在模拟过量的情况下，两种制剂中两种主要对乙酰氨基酚代谢物的 PK 参数之间存在微小差异。在中度过量中，两种制剂之间对乙酰氨基酚 AUC 的差异可能是由于 PEx 吸收较慢时同时代谢对乙酰氨基酚所致。
