Early clinical development of artemether-lumefantrine dispersible tablet: palatability of three flavours and bioavailability in healthy subjects

Table 1 Relative bioavailability study - pharmacokinetic parameters of artemether, dihydroartemisinin and lumefantrine in healthy subjects (n = 48)

	Treatment A dispersible tablet	Treatment B crushed tablet	Treatment C intact tablet
Artemether
t_max (hours)	2.0 (0.5-6.0)	2.0 (0.5-6.0)	2.0 (0.8-6.0)
C_max (ng/ml)	58.4 ± 32.2	48.0 ± 22.2	83.8 ± 59.7
AUC_0-tlast (h.ng/ml)	208 ± 113	195 ± 93	259 ± 150
AUC_0-inf (h.ng/ml)	281 ± 120 (n = 24)*	261 ± 116 (n = 20)*	330 ± 158 (n = 33)*
t_1/2 (hours)	2.2 ± 1.5 (n = 29, 60%)*	2.7 ± 2.2 (n = 25, 52%)*	2.3 ± 1.9 (n = 36, 75%)*
Dihydroartemisinin
t_max (hours)	2.0 (0.8-6.0)	2.5 (1.0-8.0)	2.0 (0.8-6.0)
C_max (ng/ml)	57.3 ± 24.9	50.0 ± 18.9	90.4 ± 48.9
AUC_0-tlast (h.ng/ml)	206 ± 81	199 ± 84	285 ± 98
AUC_0-inf (h.ng/ml)	266 ± 80 (n = 26)*	261 ± 84 (n = 25)*	326 ± 103 (n = 38)*
t_1/2 (hours)	2.1 ± 0.9 (n = 28, 58%)*	2.2 ± 1.1 (n = 27, 56%)*	2.3 ± 1.5 (n = 39, 81%)*
Lumefantrine
t_max (hours)	8.0 (6.0-12.0)	8.0 (6.0-12.0)	8.0 (5.0-12.0)
C_max (μg/ml)	9.9 ± 3.0	10.8 ± 2.8	9.8 ± 4.2
AUC_0-tlast (h.μg/ml)	262 ± 107	291 ± 106	243 ± 117
AUC_0-inf (h.μg/ml)	279 ± 106 (n = 46)*	316 ± 119 (n = 47)*	281 ± 133 (n = 40)*
t_1/2 (hours)	118 ± 55 (n = 46, 96%)*	115 ± 32 (n = 47, 98%)*	119 ± 51 (n = 41, 85%)*

*Reduced sample size because log-linear regression analysis did not allow for a proper assessment of the terminal elimination rate constant (adjusted r² < 0.75) or extrapolated area contributed > 20% of the total AUC_0-inf.
Data are median (range) for t_max and mean ± SD for all other parameters. A single oral dose of 80 mg of artemether and 480 mg of lumefantrine was administered.

ISSN: 1475-2875