Drug Research Unit, Department of Clinical Pharmacy, University of California, San Francisco, CA, United States of America.
Department of Pharmacology and Therapeutics, Makerere University College of Health Sciences, Kampala, Uganda.
PLoS One. 2018 Aug 16;13(8):e0202082. doi: 10.1371/journal.pone.0202082. eCollection 2018.
Lumefantrine is a long-acting antimalarial drug with an elimination half-life of over 3 days and protein binding of 99 percent. Correlation of lumefantrine concentrations from capillary plasma via fingerprick (Cc) versus venous plasma (Cv) remains to be defined.
Venous and capillary plasma samples were collected simultaneously from children, pregnant women, and non-pregnant adults at 2, 24, 120hr post last dose of a standard 3-day artemether-lumefantrine regimen they received for uncomplicated malaria. Some of the enrolled children and pregnant women were also HIV-infected. Samples were analyzed via liquid chromatography tandem mass spectrometry. Linear regression analysis was performed using the program Stata® SE12.1.
In children, the linear regression equations for Cc vs Cv at 2, 24, and 120hr (day 7) post dose are [Cc] = 1.05*[Cv]+95.0 (n = 142, R2 = 0.977), [Cc] = 0.995*[Cv]+56.7 (n = 147, R2 = 0.990) and [Cc] = 0.958*[Cv]+18.6 (n = 139, R2 = 0.994), respectively. For pregnant women, the equations are [Cc] = 1.04*[Cv]+68.1 (n = 43, R2 = 0.990), [Cc] = 0.997*[Cv]+37.3 (n = 43, R2 = 0.993) and [Cc] = 0.941*[Cv]+11.1 (n = 41, R2 = 0.941), respectively. For non-pregnant adults, the equations are [Cc] = 1.05*[Cv]-117 (n = 32, R2 = 0.958), [Cc] = 0.962*[Cv]+9.21 (n = 32, R2 = 0.964) and [Cc] = 1.04*[Cv]-40.1 (n = 32, R2 = 0.988), respectively. In summary, a linear relationship with a slope of ~1 was found for capillary and venous lumefantrine levels in children, pregnant women and non-pregnant adults at 2hr, 24hr and 120hr post last dose, representing absorption, distribution, and elimination phases.
Capillary and venous plasma concentration of lumefantrine can be used interchangeably at 1:1 ratio. Capillary sampling method via finger prick is a suitable alternative for sample collection in clinical studies.
盐酸阿莫地喹是一种长效抗疟药，消除半衰期超过 3 天，蛋白结合率为 99%。通过指尖（Cc）与静脉血（Cv）检测的青蒿琥酯-盐酸阿莫地喹浓度之间的相关性仍有待确定。
在接受标准的 3 天青蒿琥酯-盐酸阿莫地喹治疗方案治疗无并发症疟疾的儿童、孕妇和非孕妇成年人中，在末次剂量后 2、24 和 120 小时同时采集静脉和毛细血管血浆样本。一些入组的儿童和孕妇也感染了 HIV。通过液相色谱串联质谱法进行分析。使用 Stata® SE12.1 程序进行线性回归分析。
在儿童中，2、24 和 120 小时（第 7 天）后 Cc 与 Cv 的线性回归方程为[Cc]=1.05*[Cv]+95.0（n=142，R2=0.977），[Cc]=0.995*[Cv]+56.7（n=147，R2=0.990）和[Cc]=0.958*[Cv]+18.6（n=139，R2=0.994）。对于孕妇，方程分别为[Cc]=1.04*[Cv]+68.1（n=43，R2=0.990），[Cc]=0.997*[Cv]+37.3（n=43，R2=0.993）和[Cc]=0.941*[Cv]+11.1（n=41，R2=0.941）。对于非孕妇成年人，方程分别为[Cc]=1.05*[Cv]-117（n=32，R2=0.958），[Cc]=0.962*[Cv]+9.21（n=32，R2=0.964）和[Cc]=1.04*[Cv]-40.1（n=32，R2=0.988）。总之，在儿童、孕妇和非孕妇成年人末次剂量后 2 小时、24 小时和 120 小时，毛细血管和静脉血中的青蒿琥酯-盐酸阿莫地喹水平呈线性关系，斜率约为 1，代表吸收、分布和消除阶段。
毛细血管和静脉血中的青蒿琥酯-盐酸阿莫地喹浓度可以以 1:1 的比例互换。通过指尖刺血进行毛细血管采样是临床研究中采集样本的合适替代方法。
