TY - JOUR
T1 - Drug-development concepts as guides for optimizing clinical trials of supplemental zinc for populations at risk of deficiency or diarrhea
AU - Alpers, David
AU - Young, Graeme
AU - Tran, Cuong
AU - Mortimer, Elissa
AU - Gopalsamy, Geetha
AU - Krebs, Nancy
AU - Manary, Mark
AU - Ramakrishna, Balakrishnan
AU - Binder, Henry
AU - Brown, Ian
AU - Miller, Leland
PY - 2017/3
Y1 - 2017/3
N2 - Studies on the efficacy of zinc supplementation for treatment or prevention of diarrhea have shown an inconsistent effect in populations at risk for zinc deficiency. Unlike drugs, which have no preexisting presence in the body, endogenous zinc must be assessed pharmacokinetically by isotope tracer studies. Although such methods have produced much data, very few studies have estimated the dose and the timing of dosing of zinc supplementation. This review examines drug kinetics used to establish the best dose, the timing of such doses, and the mechanism of action through pharmacodynamic markers and applies them, where possible, to zinc supplements. The findings reveal that little is known, especially in children at highest risk of zinc deficiency. Key data missing to inform proper dosing, whether for treatment of disease or for preventive nutrient supplementation, are noted. Addressing these uncertainties could improve study design, leading to future studies of zinc supplements that might be of greater benefit.
AB - Studies on the efficacy of zinc supplementation for treatment or prevention of diarrhea have shown an inconsistent effect in populations at risk for zinc deficiency. Unlike drugs, which have no preexisting presence in the body, endogenous zinc must be assessed pharmacokinetically by isotope tracer studies. Although such methods have produced much data, very few studies have estimated the dose and the timing of dosing of zinc supplementation. This review examines drug kinetics used to establish the best dose, the timing of such doses, and the mechanism of action through pharmacodynamic markers and applies them, where possible, to zinc supplements. The findings reveal that little is known, especially in children at highest risk of zinc deficiency. Key data missing to inform proper dosing, whether for treatment of disease or for preventive nutrient supplementation, are noted. Addressing these uncertainties could improve study design, leading to future studies of zinc supplements that might be of greater benefit.
KW - Drug-development framework
KW - Pharmacodynamics
KW - Pharmacokinetics
KW - Zinc
KW - Zinc deficiency
KW - Zinc supplementation
UR - http://www.scopus.com/inward/record.url?scp=85033462504&partnerID=8YFLogxK
U2 - 10.1093/nutrit/nuw065
DO - 10.1093/nutrit/nuw065
M3 - Article
VL - 75
SP - 147
EP - 162
JO - Nutrition Reviews
JF - Nutrition Reviews
SN - 0029-6643
IS - 3
ER -