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

Abstract

BackgroundLumefantrine 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.MethodsVenous 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.ResultsIn 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.ConclusionsCapillary 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.

The Impact of Extended Treatment With Artemether-lumefantrine on Antimalarial Exposure and Reinfection Risks in Ugandan Children With Uncomplicated Malaria: A Randomized Controlled Trial

“…Capillary and venous measurements of both artemether and DHA were found to have a 1:1 linear relationship, and for lumefantrine, a 1:1 correlation was previously found [ 32 ]. PK parameters for 3- and 5-day episodes (n = 50 each) with complete intensive PK sampling are summarized in Table 2 and Figure 2 A and B .…”

The effect of sickle cell genotype on the pharmacokinetic properties of artemether-lumefantrine in Tanzanian children

“…Overall exposure (AUC) for LUM, which is correlated with treatment outcome, was within the range previously reported across a range of studies as summarised in Table 4 . While the use of DBS sampling versus plasma concentrations in the other studies might bias the present AUC estimate, the inclusion of plasma samples in the present pharmacokinetic modelling along with reports that mixed capillary and venous LUM concentrations correlate with a 1:1 ratio ( Huang et al, 2018 ) suggest that this was not significant. The non-significant trend to a higher AUC from AA to AS and SS genotypes might become significant with a larger sample size but, if present, would tend to reduce the risk of treatment failure in children with SCT or SCD.…”

Comparison of lumefantrine, mefloquine, and piperaquine concentrations between capillary plasma and venous plasma samples in pregnant women with uncomplicated falciparum and vivax malaria

“…This can also be assessed using capillary blood samples. There have been a few studies directly comparing venous and capillary blood antimalarial drug concentrations ( 3 – 9 ) and only one cohort included pregnant women ( 3 , 7 ). We assessed how precisely and reliably venous plasma drug concentrations of three major antimalarials, namely lumefantrine, mefloquine, and piperaquine, could be predicted by using capillary plasma drug concentrations in pregnant women.…”