Effect of co-administered fat on the tolerability, safety and pharmacokinetic properties of dihydroartemisinin-piperaquine in Papua New Guinean children with uncomplicated malaria.

Moore, BR; Benjamin, JM; Salman, S; Griffin, S; Ginny, E; Page-Sharp, M; Robinson, LJ; Siba, P; Batty, KT; Mueller, I; Davis, TM

Author(s): Moore, BR; Benjamin, JM; Salman, S; Griffin, S; Ginny, E; Page-Sharp, M; Robinson, LJ; Siba, P; Batty, KT; Mueller, I; Davis, TM;
Details: Publication Year 2014-07-21,Volume 58,Issue #10,Page 5784-5794
Journal Title: Antimicrobial agents and chemotherapy
Publication Type: JOURNAL ARTICLE
Abstract: Co-administration of dihydroartemisinin-piperaquine (DHA-PQ) with fat may improve bioavailability and antimalarial efficacy, but it might also increase toxicity. There have been no studies of these potential effects in the pediatric age-group. The tolerability, safety, efficacy and pharmacokinetics of DHA-PQ administered with or without 8.5 g fat were investigated in 30 Papua New Guinean children aged 5-10 years diagnosed with uncomplicated falciparum malaria. Three daily 2.5:11.5 mg base/kg doses were given with water (n=14, Group A) or milk (n=16, Group B), with regular clinical/laboratory assessment and blood sampling over 42 d. Plasma PQ was assayed by high performance liquid chromatography with ultraviolet detection and DHA using liquid chromatography-mass spectrometry. Compartmental pharmacokinetic models for PQ and DHA were developed using a population-based approach. DHA-PQ was generally well tolerated and initial fever and parasite clearance were prompt. There were no differences in the areas under the concentration-time curve (AUC0-∞) for PQ (medians 42,140 vs 37,241 μg.h/liter in Groups A and B, respectively, P=0.21) or DHA (4,047 vs 4,190 μg.h/liter, P=0.67). There were also no significant between-group differences in prolongation of the corrected electrocardiographic QT interval (QTc) initially during follow-up, but the QTc tended to be higher in Group B children at 24 h (mean±SD 15±10 vs 6±15 msec(0.5) in Group A, P=0.067) and 168 h (10±18 vs 1±23 msec(0.5), P=0.24) when plasma PQ concentrations were relatively low. A small amount of fat does not change the bioavailability of DHA-PQ in children but a delayed persistent effect on ventricular repolarization cannot be excluded.
Publisher: AMER SOC MICROBIOLOGY
Research Division(s): Infection And Immunity
Link To PubMed Central Version: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4187992/
Publisher's Version: https://doi.org/10.1128/AAC.03314-14
NHMRC Grants: NHMRC/1043345, NHMRC/1016443,
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2014-07-30 02:49:59

Last Modified: 2015-05-22 10:18:11