TABLE 4.

Antimalarial drug clearance from clinical studies in children compared to interpolated CL from simple allometry and MLP correction

Drug	Allometric exponenta		Interpolated CL (liters/h/kg)a		Clinical studyb
	Simple allometry	MLP correction	Simple allometry	MLP correction	CL (liters/h/kg)	Wt (kg)	Reference
Dihydroartemisinin	0.85	1.31	2.21	0.48	2.16	13	149
Artemether	0.66	1.18	1.52	0.35	1.5	9.5	150
Piperaquine	0.96	1.46	1.40	0.50	1.85c	16	56
Piperaquine	0.96	1.46	1.39	0.57	0.85c	19.1	57
Mefloquine	0.52	1.0	0.068	0.023	0.046d	9.5e	151
Mefloquine	0.52	1.0	0.068	0.023	0.048d	9.5e	152
Mefloquine	0.52	1.0	0.045	0.024	0.026d	23	153
Quininef	0.40	0.93	0.37	0.13	0.24	15.4	118

^aAllometry was conducted in healthy controls; CL/F was determined for piperaquine and mefloquine.

^bData from studies in malaria-infected children; CL/F was determined for piperaquine and mefloquine.

^cPiperaquine CL/F was determined from studies of piperaquine-dihydroartemisinin in malaria-infected children. There is no significant difference in piperaquine clearance when piperaquine is administered alone or in combination with dihydroartemisinin (148). One recent study reported a CL/F of 0.57 liter/h/kg; however, the data were pooled from a previous study of piperaquine-dihydroartemisinin (57) and an investigation of piperaquine-artemisinin (12). A report of a piperaquine CL/F of 0.42 liter/h/kg from capillary blood samples could not be compared directly to investigations using venous plasma samples for determination of piperaquine pharmacokinetic parameters (13).

^dMefloquine CL/F was determined from studies of mefloquine-sulfadoxine-pyrimethamine in malaria-infected children. Mefloquine clearance may be lower when mefloquine is administered in combination with sulfadoxine and pyrimethamine (101).

^eMalaria-infected children were all <2 years of age in these studies; the mean age was 1.6 years.

^fAll quinine data are from studies in healthy controls.