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

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 (C(c)) versus venous plasma (C(v)) 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 C(c) vs C(v) at 2, 24, and 120hr (day 7) post dose are [C(c)] = 1.05*[C(v)]+95.0 (n = 142, R(2) = 0.977), [C(c)] = 0.995*[C(v)]+56.7 (n = 147, R(2) = 0.990) and [C(c)] = 0.958*[C(v)]+18.6 (n = 139, R(2) = 0.994), respectively. For pregnant women, the equations are [C(c)] = 1.04*[C(v)]+68.1 (n = 43, R(2) = 0.990), [C(c)] = 0.997*[C(v)]+37.3 (n = 43, R(2) = 0.993) and [C(c)] = 0.941*[C(v)]+11.1 (n = 41, R(2) = 0.941), respectively. For non-pregnant adults, the equations are [C(c)] = 1.05*[C(v)]-117 (n = 32, R(2) = 0.958), [C(c)] = 0.962*[C(v)]+9.21 (n = 32, R(2) = 0.964) and [C(c)] = 1.04*[C(v)]-40.1 (n = 32, R(2) = 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.