title: Special populations and pharmacogenetic issues in tuberculosis drug development and clinical research.
abstract: Special populations, including children and pregnant women, have been neglected in tuberculosis drug development. Patients in developing countries are inadequately represented in pharmacology research, and postmarketing pharmacovigilance activities tend to be rudimentary in these settings. There is an ethical imperative to generate evidence at an early stage to support optimal treatment in these populations and in populations with common comorbid conditions, such as diabetes and human immunodeficiency virus (HIV) infection. This article highlights the research needed to support equitable access to new antituberculosis regimens. Efficient and opportunistic pharmacokinetic study designs, typically using sparse sampling and population analysis methods, can facilitate optimal dose selection for children and pregnant women. Formulations suitable for children should be developed early and used in pharmacokinetic studies to guide dose selection. Drug-drug interactions between commonly coprescribed medications also need to be evaluated, and when these are significant, alternative approaches should be sought. A potent rifamycin-sparing regimen could revolutionize the treatment of adults and children requiring a protease inhibitor as part of antiretroviral treatment regimens for HIV infection. A sufficiently wide formulary of drugs should be developed for those with contraindications to the standard approaches. Because genetic variations may influence an individual's response to tuberculosis treatment, depending on the population being treated, it is important that samples be collected and stored for pharmacogenetic study in future clinical trials.
authors.affiliation: Division of Clinical Pharmacology.
authors.forename: Helen
authors.initials: H
authors.lastname: McIlleron
authors.affiliation: Division of Clinical Pharmacology, Children's Mercy Hospital Department of Pediatrics, School of Medicine, University of Missouri-Kansas City, Missouri.
authors.forename: Susan
authors.initials: S
authors.lastname: Abdel-Rahman
authors.affiliation: Division of Diabetic Medicine and Endocrinology, Department of Medicine, Faculty of Health Sciences, University of Cape Town and Groote Schuur Hospital, South Africa.
authors.forename: Joel Alex
authors.initials: JA
authors.lastname: Dave
authors.affiliation: Division of Clinical Pharmacology.
authors.forename: Marc
authors.initials: M
authors.lastname: Blockman
authors.affiliation: Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, United Kingdom.
authors.forename: Andrew
authors.initials: A
authors.lastname: Owen
mesh_terms: D000995:Antitubercular Agents / Q000627:therapeutic use*; D035843:Biomedical Research; D002648:Child; D004347:Drug Interactions / Q000502:physiology; D005260:Female; D006801:Humans; D010597:Pharmacogenetics / Q000379:methods; D011247:Pregnancy; D014376:Tuberculosis / Q000188:drug therapy*
chemical_list: D000995:Antitubercular Agents
keywords: HIV; children; diabetes; efficacy; pharmacogenetic; pharmacokinetic; pregnant women; safety; special population; tuberculosis