TABLE 2.

Descriptions of population pharmacokinetic and noncompartmental studies^a

Country	Study description (authors [reference(s)])	Treatment (protocol)	Study population	Formulation	Manufacturer	No. of patients	Sampling schedule (protocol)	Sample collection	Sample storage and assay	No. of samples per patientb	LLOQ of AQ/DEAQ concn (ng/ml)
Thailandc	Effect of pregnancy on PK and PD of amodiaquine and desethylamodiaquine (Tarning and colleagues [21, 24])	AQ (10 mg/kg) daily for 3 days, 200 mg amodiaquine hydrochloride (153 mg amodiaquine base)	Pregnant women (ages, 16 to 39 yr) in their 2nd and 3rd trimester (with follow-up after delivery)	AQ alone	Sanofi-Aventis, France	26 (7)d	0, 4, 24, 28, 48, 48.5, 49, 50, 51, 52, 54, 56, 58, and 72 h; 4, 5, 7, 14, 21, 28, 35, and 42 days	A sample was drawn from a catheter during the first 3 days and thereafter by venous puncture and placed into lithium heparin tubes	Samples were stored at −20°C and analyzed by LC-MS/MS	14/22 (14/22)	1/2
Kenyac	Efficacy of fixed vs nonfixed dose of ASAQ (Jullien et al. [23])	Two tablets of AS-AQ at a fixed dose (100/270 mg) or 4 tablets of AS (50 mg) + 4 tablets of AQ (153 mg) daily for 3 days, 353/200 mg amodiaquine hydrochloride (153/270 mg amodiaquine base)	Adults (ages, 18 to 60 yr)	AS + AQ at a fixed dose and as a loose formulation	Sanofi-Aventis, France	53	Before 1st dose, 15 min to 4 h after 1st dose, 15 min to 4 h after 2nd dose, just before 3rd dose, 15 min to 4 h after 3rd dose, days 7, 14, 21, and 28		Samples were analyzed by HPLC	4/8	1/1
Ugandae	Determine PK parameters for AS and AQ in children (Mwesigwa et al. [25])	AS (50-mg tablets at 4 mg/kg twice a day for 3 days) + AQ (200-mg tablets at 10 mg/kg once a day on the first 2 days and 5 mg/kg on the third day), 200 mg amodiaquine hydrochloride (153 mg amodiaquine base)	Children (ages, 5 to 13 yr)	AS + AQ, loose formulation	Sanofi-Aventis, France	20	Just prior to 3rd dose and at 2, 4, 8, 24, and 120 h after 3rd dose	A venous sample was drawn into potassium oxalate-sodium fluoride tubes	Samples were stored at −80°C and analyzed by LC-MS/MS	2/6	5/5
Burkina Fasoc	Compare bioavailability of fixed doses of AS and AQ vs AS and AQ separately (Stepniewska et al. [22])	AS-AQ at a fixed dose (one dose of 25/67.5 mg/kg for children <12 mo of age or two doses for children ages 12 to 60 mo) or AS (50-mg tablet, a half tablet for children <12 mo of age and one tablet for children ages 12 to 60 mo) + AQ (153 mg, a half tablet for children <12 mo of age and one tablet for children ages 12 to 60 mo) daily for 3 days, 200 mg amodiaquine hydrochloride (153 mg amodiaquine base)	Children (ages, 1 to 5 yr)	AS + AQ at a fixed dose and as a loose formulation	Sanofi-Aventis, France	61	Before the 1st dose, 4 h after the 3rd dose, and then at days 7 and 14 and days 21 and 28	A venous sample was collected in lithium heparin tubes	Samples were stored at −20°C and analyzed by LC-MS/MS	2/3	1/1
Ghanac	Compare the effect of AS on AQ (comparison between AQ and loose formulations of AS and AQ) (Adjei et al. [20])	AQ (10-mg/kg single dose) or AS (4-mg/kg single dose) + AQ (10-mg/kg single dose) daily for 3 days, 200 mg amodiaquine hydrochloride (153 mg amodiaquine base)	Children (ages, 1 to 14 yr)	AS + AQ, loose formulation	Pfizer, Dakar, Senegal	101	Before the dose on days 3 and 7	A venous sample was collected into heparinized polypropylene tubes	Samples were stored at −20°C and analyzed by HPLC	1/2	10/10

^aAll samples were venous plasma. AS, artesunate; AQ, amodiaquine; LLOQ, lower limit of quantification; DEAQ, desethylamodiaquine; LC-MS/MS, liquid chromatography-tandem mass spectrometry; HPLC, reverse-phase high-performance liquid chromatography.

^bMedian number of amodiaquine/desethylamodiaquine samples per subject; values in parentheses are for the same women at 3 months postdelivery.

^cPopulation PK study.

^dThe same women were sampled again at 3 months postdelivery during another malaria episode.

^eNoncompartmental pharmacokinetic analysis.