Use of saliva and capillary blood samples as substitutes for venous blood sampling in pharmacokinetic investigations of artemisinin.

Abstract

Artemisinin concentrations in venous plasma, capillary plasma and saliva were compared. Eighteen Vietnamese adults with uncomplicated falciparum malaria were treated with artemisinin. Saliva, capillary and venous plasma were sampled and analysed for artemisinin using high-performance liquid chromatography with an ultraviolet detector (HPLC-UV). Artemisinin capillary plasma concentrations were highly correlated to its venous plasma levels (correlation coefficient r = 0.92). Capillary/venous concentration ratios were significantly higher than unity at 30 min and 60 min after drug intake, indicating an arterial-venous concentration difference. Artemisinin unbound fraction in plasma averaged 0.14 (SD = 0.03) and was independent of drug concentration (114-1001 ng/ml). Artemisinin concentrations in saliva were comparable to its unbound levels in plasma. Saliva levels were more highly correlated to unbound capillary plasma (r = 0.85) than to unbound venous plasma concentrations (r = 0.77). No statistically significant differences were found between the saliva, unbound venous and unbound capillary area under the curve (AUC) values. Capillary plasma or saliva may replace venous plasma in pharmacokinetic investigations of artemisinin. Due to the ease of collection and handling, saliva sampling can be a simple approach in field studies of artemisinin, although the lower saliva concentrations require more sensitive analytical methods.