Table 1 The main pharmacokinetic parameters of artemisinin (QHS) and its phase I/II metabolites (deoxy-QHS, monohydroxylated deoxy-QHS, monohydroxylated QHS, dihydroxylated QHS, the glucuronide of monohydroxylated deoxy-QHS, and the glucuronide of monohydroxylated QHS) after one-day and two-day oral administrations of QHS-PQ (1.8 mg/kg of QHS plus 10.6 mg/kg piperaquine) to 14 healthy Chinese subjects (mean ± sd)

1-day

QHS

0.14 ± 0.08**

304.3 ± 191.7

1.8 (0.75, 3.0)

3.2 ± 0.9

9.81 ± 8.25**

N.A.

DeoxyQHS

0.09 ± 0.05**

71.0 ± 46.1*

2.2 (1.25, 4.0)

7.1 ± 0.6

14.71 ± 8.41**

0.67 ± 0.25

M1

3.72 ± 1.59**

1527.4 ± 721.7

7.0 (3.0, 12.0)

11.6 ± 0.7**

0.36 ± 0.27**

28.80 ± 11.31**

M2

1.66 ± 0.83**

2378.5 ± 1135.6**

2.1 (1.25, 3.0)

4.0 ± 0.6

0.80 ± 0.52**

12.61 ± 4.56

M3

0.49 ± 0.30*

451.6 ± 299.2

3.3 (1.25, 6.0)

5.7 ± 1.2

7.55 ± 15.62*

3.80 ± 2.90

M4

0.02 ± 0.01**

22.8 ± 17.1**

1.9 (0.75, 3.0)

4.4 ± 2.0

135.13 ± 141.70**

0.007 ± 0.01**†

M5

0.02 ± 0.01**

58.7 ± 37.7**

1.7 (0.75, 3.0)

2.4 ± 0.8

82.54 ± 66.47**

0.02 ± 0.02**‡

2-day

QHS

0.09 ± 0.05**

221.4 ± 117.9

1.4 (0.75, 1.75)

2.9 ± 0.9

16.60 ± 14.79**

N.A.

DeoxyQHS

0.06 ± 0.04**

55.6 ± 33.3*

2.3 (1.25. 5.0)

6.2 ± 1.5

24.71 ± 20.75**

0.79 ± 0.47

M1

3.15 ± 1.42**

1382.3 ± 680.6

3.5 (1.25, 8.0)

9.8 ± 0.7**

0.43 ± 0.30**

43.08 ± 27.12**

M2

1.25 ± 0.62**

1973.9 ± 1084.4**

2.0 (1.25, 5.0)

3.9 ± 0.6

1.15 ± 0.92**

16.91 ± 10.18

M3

0.39 ± 0.26*

366.3 ± 250.0

3.0 (1.25, 5.0)

5.6 ± 1.3

4.43 ± 5.00*

5.82 ± 6.28

M4

0.03 ± 0.02**

35.4 ± 15.7**

1.9 (0.75, 4.0)

4.7 ± 1.5

51.54 ± 31.52**

0.01 ± 0.01**†

M5

0.04 ± 0.01**

99.9 ± 51.7**

1.5 (0.75, 4.0)

2.7 ± 0.5

29.85 ± 11.98**

0.05 ± 0.05**‡

Geometric mean ratios (90% CI)

QHS

0.64 (0.56, 0.73)**

0.73 (0.56, 0.94)

N.A.

0.92 (0.78, 1.09)

1.69 (1.48, 1.94)**

N.A.

DeoxyQHS

0.68 (0.58, 0.79)**

0.78 (0.69, 0.89)*

N.A.

0.89 (0.79, 0.99)

1.68 (1.45, 1.95)**

1.18 (0.97, 1.43)

M1

0.85 (0.79, 0.91)**

0.90 (0.80, 1.03)

N.A.

0.84 (0.81, 0.88)**

1.18 (1.10, 1.26)**

1.50 (1.31, 1.71)**

M2

0.75 (0.68, 0.83)**

0.83 (0.73, 0.95)**

N.A.

0.98 (0.89, 1.07)

1.43 (1.30, 1.58)**

1.34 (1.18, 1.53)

M3

0.79 (0.44, 1.40)*

0.82 (0.70, 0.96)

N.A.

0.96 (0.89, 1.04)

0.59 (0.33, 1.05)*

1.53 (1.13, 2.07)

M4

1.66 (1.30, 2.12)**

1.55 (1.26, 1.91)**

N.A.

1.07 (0.91, 1.26)

0.38 (0.30, 0.49)**

1.45 (1.13, 1.88)**†

M5

1.98 (1.62, 2.41)**

1.70 (1.41, 2.05)**

N.A.

1.12 (0.98, 1.29)

0.36 (0.30, 0.44)**

2.95 (2.43, 3.58)**‡