Table 1.

Population mean pharmacokinetic parameters for antimalarial drugs in human clinical trials

Antimalarial	Gender	Pregnant	Malaria	Model	ka	tlag	CL/F	V1/F	Q/F	V2/F	Q2/F	V3/F	Reference.
	(M/F)	(Y/N)	(falci/viv)		(1 h−1)	(h)	(l h−1)	(l)	(l h−1)	(l)	(l h−1)	(l)
Pharmacokinetics in adults
Dihydroartemisinin	M/F	N	falci	1-comp.	0.820	0.210	47.5	32.1	–	–	–	–	[66]
	F	Y	falci	1-comp.	1.19	0.420	88.5*	232*	–	–	–	–	[67]
	F	Y	falci	1-comp.	4.59	0.627	91.6	91.4	–	–	–	–	[68]
	F	N	falci	1-comp.	4.59	0.627	64.0	91.4	–	–	–	–	[68]
	F	Y	falci	1-comp.	8.15†	–	78.0	129	–	–	–	–	[71]
	F	N	falci	1-comp.	8.15†	–	78.0	129	–	–	–	–	[71]
Mefloquine	M/F	N	falci	1-comp.	0.290	–	1.40*	453*	–	–	–	–	[72]
(RS enantiomer)	M/F	N	falci	2-comp.	0.198	–	3.51	559	2.54	395	–	–	[77]
(SR enantiomer)	M/F	N	falci	2-comp.	0.255	–	0.602	261	0.942	287	–	–	[77]
	F	N	falci	1-comp.	–	–	1.87*	440*	–	–	–	–	[106]
	F	Y	falci	1-comp.	–	–	2.38*	549*	–	–	–	–	[106]
Lumefantrine	M/F	N	falci	2-comp.	0.170	–	7.04	103	4.08	272	–	–	[76]
	F	Y	falci	2-comp.	0.0588	1.67	6.11	20.2	1.82	160	–	–	[78]
Piperaquine	F	N	falci	3-comp.	2.88†	–	60.2	3070	427	4440	160	31400	[71]
	F	Y	falci	3-comp.	2.88†	–	87.3	3070	427	4440	160	31400	[71]
	M/F	N	falci/viv	2-comp.	0.083	0.490	42.3*	682*	129*	23122*	–	–	[79]
	M/F	N	falci	2-comp.	0.717	–	66.0	8660	131	24000	–	–	[80]
	F	Y/N	falci	3-comp.	2.35†	–	44.6	1820	47.7	15900	352	7520	[81]
Pyrimethamine	F	Y	falci	2-comp.	1.87	–	1.04	174	0.439	184	–	–	[84]
	F	N	falci	2-comp.	1.69	–	0.707	108	0.402	67.4	–	–	[84]
Sulphadoxine	F	Y	falci	2-comp.	0.475	–	0.0690	12.3	0.0041	0.860	–	–	[84]
	F	N	falci	2-comp.	0.754	–	0.0470	10.6	0.0039	0.810	–	–	[84]
Amodiaquine†	F	Y	viv	2-comp.	0.515	0.395	2530	4850	2750	29000	–	–	[87]
Desethylamodiaquine†	F	Y	viv	3-comp.	–	–	34.3	197	161	2670	26.0	5700	[87]
Pharmacokinetics in children
Dihydroartemisinin	M/F	N	falci	1-comp.	4.27	–	8.27*	29.7*	–	–	–	–	[69]
Lumefantrine	M/F	N	falci	1-comp.	0.820	1.92	1.08*	125*	–	–	–	–	[73]
Mefloquine	M/F	N	falci	1-comp.	0.290	–	1.28*	375*	–	–	–	–	[74]
Mefloquine (split dose)	M/F	N	falci	1-comp.	0.290	–	1.03*	350*	–	–	–	–	[74]
Piperaquine	M/F	N	falci/viv	2-comp.	0.075	–	29.6*	315*	104*	10507*	–	–	[79]
	M/F	N	falci	3-comp.	1.4†	–	7.50	247	13.1	254	10.8	3340	[82]
Pyrimethamine	M/F	N	falci	1-comp.	1.48	–	0.258	46.0	–	–	–	–	[83]
Sulphadoxine	M/F	N	falci	1-comp.	0.630	–	0.0151	3.09	–	–	–	–	[83]
Amodiaquine‡	M/F	N	falci	2-comp.	0.13	–	224*	187*	272*	4976*	–	–	[85]
Desethylamodiaquine‡	M/F	N	falci	2-comp.	–	–	10.5*	205*	20.8*	998*	–	–	[85]

Falci is uncomplicated falciparum malaria, viv is uncomplicated vivax malaria, comp. compartment; k_a is the rate constant for first order absorption, t_lag is the lag time in oral absorption, CL/F is the apparent central compartment clearance, V₁/F is the apparent central volume of distribution, Q/F is the apparent inter-compartmental clearance from the shallow peripheral compartment, V₂/F is the apparent shallow peripheral volume of distribution, Q₂/F is the apparent inter-compartmental clearance from the deep peripheral compartment, V₃/F is the apparent deep peripheral volume of distribution.

^*Calculated for mean or median bodyweight of patient population in the study.

^†Models in which the kinetics of drug absorption are described by a series of transit compartments. The number of transit compartments was seven for dihydroartemisinin and five for piperaquine ([71]), three for piperaquine ([81]) and two for piperaquine ([82]).

^‡Describes parent (amodiaquine) and metabolite (desethylamodiaquine) models.