T Gordi1, T N Hai, N M Hoai, M Thyberg, M Ashton. 1. Division of Biopharmaceutics and Pharmacokinetics, Uppsala University, Box 580, S-75123 Uppsala, Sweden.
Abstract
OBJECTIVES: Artemisinin concentrations in venous plasma, capillary plasma and saliva were compared. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.
OBJECTIVES:Artemisinin concentrations in venous plasma, capillary plasma and saliva were compared. METHODS: 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). RESULTS: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. CONCLUSIONS: 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.
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