Strong correlation of lumefantrine concentrations in capillary and venous plasma from malaria patients

Abstract

Background 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. Methods 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. Results 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. Conclusions 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.