title: Drug-development concepts as guides for optimizing clinical trials of supplemental zinc for populations at risk of deficiency or diarrhea.
abstract: 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.
authors.affiliation: School of Medicine, Washington University, St Louis, Missouri, USA.
authors.forename: David H
authors.initials: DH
authors.lastname: Alpers
authors.affiliation: School of Medicine, Flinders University of South Australia, Adelaide, South Australia, Australia.
authors.forename: Graeme P
authors.initials: GP
authors.lastname: Young
authors.affiliation: CSIRO Health and Biosecurity, Adelaide, South Australia, Australia.|School of Medicine, Faculty of Health Sciences, The University of Adelaide, South Australia, Australia.
authors.forename: Cuong D
authors.initials: CD
authors.lastname: Tran
authors.affiliation: School of Medicine, Flinders University of South Australia, Adelaide, South Australia, Australia.
authors.forename: Elissa K
authors.initials: EK
authors.lastname: Mortimer
authors.affiliation: School of Medicine, Flinders University of South Australia, Adelaide, South Australia, Australia.|CSIRO Health and Biosecurity, Adelaide, South Australia, Australia.
authors.forename: Geetha L
authors.initials: GL
authors.lastname: Gopalsamy
authors.affiliation: Section of Nutrition, Department of Pediatrics, University of Colorado School of Medicine, Denver, Colorado, USA.
authors.forename: Nancy F
authors.initials: NF
authors.lastname: Krebs
authors.affiliation: School of Medicine, Washington University, St Louis, Missouri, USA.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Manary
authors.affiliation: School of Medicine, SRM University, Kancheepuram, Tamil Nadu, India.
authors.forename: Balakrishnan S
authors.initials: BS
authors.lastname: Ramakrishna
authors.affiliation: School of Medicine, Yale University, New Haven, Connecticut, USA.
authors.forename: Henry J
authors.initials: HJ
authors.lastname: Binder
authors.affiliation: School of Medicine, Flinders University of South Australia, Adelaide, South Australia, Australia.
authors.forename: Ian L
authors.initials: IL
authors.lastname: Brown
authors.affiliation: Section of Nutrition, Department of Pediatrics, University of Colorado School of Medicine, Denver, Colorado, USA.
authors.forename: Leland V
authors.initials: LV
authors.lastname: Miller
mesh_terms: D002986:Clinical Trials as Topic; D003967:Diarrhea / Q000188:drug therapy*; D019587:Dietary Supplements; D004347:Drug Interactions; D018565:Food-Drug Interactions; D006801:Humans; D018673:Nutrition Policy; D012307:Risk Factors; D015032:Zinc / Q000008:administration & dosage* / Q000172:deficiency* / Q000493:pharmacokinetics
chemical_list: D015032:Zinc
keywords: drug-development framework; pharmacodynamics; pharmacokinetics; zinc; zinc deficiency; zinc supplementation