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Review

Falls: The Adverse Drug Reaction of the Elderly and the Impact of Pharmacogenetics

, , , &
Pages 1281-1297 | Received 27 Jan 2017, Accepted 14 Jun 2017, Published online: 04 Aug 2017

References

  • Huang AR , MalletL , RochefortCM , EgualeT , BuckeridgeDL , TamblynR . Medication-related falls in the elderly . Drugs Aging29 ( 5 ), 359 – 376 ( 2012 ).
  • Scuffham P , ChaplinS , LegoodR . Incidence and costs of unintentional falls in older people in the United Kingdom . J. Epidemiol. Commun. Health57 ( 9 ), 740 – 744 ( 2003 ).
  • Tinetti ME , WilliamsCS . Falls, injuries due to falls, and the risk of admission to a nursing home . N. Engl. J. Med.337 ( 18 ), 1279 – 1284 ( 1997 ).
  • Bergen G , StevensMR , BurnsER . Falls and fall injuries among adults aged >/=65 years – United States, 2014 . MMWR Morb. Mortal. Wkly Rep.65 ( 37 ), 993 – 998 ( 2016 ).
  • Gill TM , MurphyTE , GahbauerEA , AlloreHG . Association of injurious falls with disability outcomes and nursing home admissions in community-living older persons . Am. J. Epidemiol.178 ( 3 ), 418 – 425 ( 2013 ).
  • Hedna K , HakkarainenKM , GyllenstenH , JonssonAK , PetzoldM , HaggS . Potentially inappropriate prescribing and adverse drug reactions in the elderly: a population-based study . Eur. J. Clin. Pharmacol.71 ( 12 ), 1525 – 1533 ( 2015 ).
  • Hajjar ER , CafieroAC , HanlonJT . Polypharmacy in elderly patients . Am. J. Geriatr. Pharmacother.5 ( 4 ), 345 – 351 ( 2007 ).
  • Gurwitz JH , FieldTS , HarroldLRet al. Incidence and preventability of adverse drug events among older persons in the ambulatory setting . JAMA289 ( 9 ), 1107 – 1116 ( 2003 ).
  • Pirmohamed M , JamesS , MeakinSet al. Adverse drug reactions as cause of admission to hospital: prospective analysis of 18 820 patients . BMJ329 ( 7456 ), 15 – 19 ( 2004 ).
  • Hartikainen S , LönnroosE , LouhivuoriK . Medication as a risk factor for falls: critical systematic review . J. Gerontol. A Biol. Sci. Med. Sci.62 ( 10 ), 1172 – 1181 ( 2007 ).
  • Leipzig RM , CummingRG , TinettiME . Drugs and falls in older people: a systematic review and meta-analysis: II. Cardiac and analgesic drugs . J. Am. Geriatr. Soc.47 ( 1 ), 40 – 50 ( 1999 ).
  • Leipzig RM , CummingRG , TinettiME . Drugs and falls in older people: a systematic review and meta-analysis: I. Psychotropic drugs . J. Am. Geriatr. Soc.47 ( 1 ), 30 – 39 ( 1999 ).
  • Woolcott JC , RichardsonKJ , WiensMOet al. Meta-analysis of the impact of 9 medication classes on falls in elderly persons . Arch. Intern. Med.169 ( 21 ), 1952 – 1960 ( 2009 ).
  • Bloch F , ThibaudM , DugueB , BrequeC , RigaudAS , KemounG . Psychotropic drugs and falls in the elderly people: updated literature review and meta-analysis . J. Aging Health23 ( 2 ), 329 – 346 ( 2011 ).
  • Boyé ND , Van Der VeldeN , De VriesOJet al. Effectiveness of medication withdrawal in older fallers: results from the Improving Medication Prescribing to reduce Risk Of FALLs (IMPROveFALL) trial . Age Ageing46 ( 1 ), 142 – 146 ( 2016 ).
  • Polinder S , BoyéND , Mattace-RasoFUet al. Cost-utility of medication withdrawal in older fallers: results from the improving medication prescribing to reduce risk of FALLs (IMPROveFALL) trial . BMC Geriatr.16 ( 1 ), 179 ( 2016 ).
  • Kirchheiner J , FuhrU , BrockmöllerJ . Pharmacogenetics-based therapeutic recommendations – ready for clinical practice?Nat. Rev. Drug Discov.4 ( 8 ), 639 – 647 ( 2005 ).
  • PharmGkb dosing guidelines . www.pharmgkb.org/view/dosing-guidelines.do?source=# .
  • Ray WA , GriffinMR , SchaffnerW , BaughDK , Melton IiiLJ . Psychotropic drug use and the risk of hip fracture . N. Engl. J. Med.316 ( 7 ), 363 – 369 ( 1987 ).
  • Sterke CS , ZiereG , Van BeeckEF , LoomanCW , Van Der CammenTJ . Dose–response relationship between selective serotonin re-uptake inhibitors and injurious falls: a study in nursing home residents with dementia . Br. J. Clin. Pharmacol.73 ( 5 ), 812 – 820 ( 2012 ).
  • Hartholt KA , BeckerML , Van Der CammenTJ . Drug-induced falls in older persons: is there a role for therapeutic drug monitoring?Ther. Adv. Drug Saf.7 ( 2 ), 39 – 42 ( 2016 ).
  • E Caudle K , E KleinT , M HoffmanJet al. Incorporation of pharmacogenomics into routine clinical practice: the Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline development process . Curr. Drug Metab.15 ( 2 ), 209 – 217 ( 2014 ).
  • Kirchheiner J , NickchenK , BauerMet al. Pharmacogenetics of antidepressants and antipsychotics: the contribution of allelic variations to the phenotype of drug response . Mol. Psychiatry9 ( 5 ), 442 – 473 ( 2004 ).
  • Kirchheiner J , BrosenK , DahlMLet al. CYP2D6 and CYP2C19 genotype-based dose recommendations for antidepressants: a first step towards subpopulation-specific dosages . Acta Psychiatr. Scand.104 ( 3 ), 173 – 192 ( 2001 ).
  • Swen J , NijenhuisM , BoerADet al. Pharmacogenetics: from bench to byte – an update of guidelines . Clin. Pharmacol. Ther.89 ( 5 ), 662 – 673 ( 2011 ).
  • Cox CA , Van JaarsveldHJ , HoutermanSet al. Psychotropic drug prescription and the risk of falls in nursing home residents . J. Am. Med. Dir. Assoc.17 ( 12 ), 1089 – 1093 ( 2016 ).
  • Stingl J , BrockmöllerJ , VivianiR . Genetic variability of drug-metabolizing enzymes: the dual impact on psychiatric therapy and regulation of brain function . Mol. Psychiatry18 ( 3 ), 273 – 287 ( 2013 ).
  • Mulder H , HeerdinkER , Van IerselEE , WilminkFW , EgbertsAC . Prevalence of patients using drugs metabolized by cytochrome P450 2D6 in different populations: a cross-sectional study . Ann. Pharmacother.41 ( 3 ), 408 – 413 ( 2007 ).
  • Ensrud KE , BlackwellTL , MangioneCMet al. Central nervous system active medications and risk for falls in older women . J. Am. Geriatr. Soc.50 ( 10 ), 1629 – 1637 ( 2002 ).
  • Coupland C , DhimanP , MorrissR , ArthurA , BartonG , Hippisley-CoxJ . Antidepressant use and risk of adverse outcomes in older people: population based cohort study . BMJ343 , d4551 ( 2011 ).
  • Naples JG , KotlarczykMP , PereraS , GreenspanSL , HanlonJT . Non-tricyclic and non-selective serotonin reuptake inhibitor antidepressants and recurrent falls in frail older women . Am. J. Geriatr. Psychiatry24 ( 12 ), 1221 – 1227 ( 2016 ).
  • Waade RB , MoldenE , MartinsenMI , HermannM , RanhoffAH . Psychotropics and weak opioid analgesics in plasma samples of older hip fracture patients - detection frequencies and consistency with drug records . Br. J. Clin. Pharmacol.83 ( 7 ), 1397 – 1404 ( 2017 ).
  • Quach L , YangFM , BerrySDet al. Depression, antidepressants, and falls among community-dwelling elderly people: the MOBILIZE Boston study . J. Gerontol. A Biol. Sci. Med. Sci.68 ( 12 ), 1575 – 1581 ( 2013 ).
  • American Geriatrics Society Beers Criteria Update Expert P . American Geriatrics Society 2015 updated beers criteria for potentially inappropriate medication use in older adults . J. Am. Geriatr. Soc.63 ( 11 ), 2227 – 2246 ( 2015 ).
  • Reis M , AamoT , SpigsetO , AhlnerJ . Serum concentrations of antidepressant drugs in a naturalistic setting: compilation based on a large therapeutic drug monitoring database . Ther. Drug Monit.31 ( 1 ), 42 – 56 ( 2009 ).
  • Janus SIM , ReindersGH , Van ManenJG , ZuidemaSU , MjIJ . Psychotropic drug-related fall incidents in nursing home residents living in the eastern part of the Netherlands . Drugs R&D17 ( 2 ), 321 – 328 ( 2017 ).
  • Passaro A , VolpatoS , RomagnoniF , ManzoliN , ZulianiG , FellinR . Benzodiazepines with different half-life and falling in a hospitalized population: the GIFA study . J. Clin. Epidemiol.53 ( 12 ), 1222 – 1229 ( 2000 ).
  • Marcum ZA , WirtzHS , PettingerMet al. Anticholinergic medication use and falls in postmenopausal women: findings from the women’s health initiative cohort study . BMC Geriatr.16 ( 1 ), 1 ( 2016 ).
  • Kelly KD , PickettW , YiannakouliasNet al. Medication use and falls in community-dwelling older persons . Age Ageing32 ( 5 ), 503 – 509 ( 2003 ).
  • Leavy B , MichaëlssonK , ÅbergAC , MelhusH , BybergL . The impact of disease and drugs on hip fracture risk . Calcif. Tissue Int.100 ( 1 ), 1 – 12 ( 2017 ).
  • Gill SS , AndersonGM , FischerHDet al. Syncope and its consequences in patients with dementia receiving cholinesterase inhibitors: a population-based cohort study . Arch. Intern. Med.169 ( 9 ), 867 – 873 ( 2009 ).
  • Takkouche B , Montes-MartínezA , GillSS , EtminanM . Psychotropic medications and the risk of fracture . Drug Saf.30 ( 2 ), 171 – 184 ( 2012 ).
  • Kosk K , LuukinenH , LaippalaP , KiveläS-L . Physiological factors and medications as predictors of injurious falls by elderly people: a prospective population-based study . Age Ageing25 ( 1 ), 29 – 38 ( 1996 ).
  • Welk B , McarthurE , FraserLAet al. The risk of fall and fracture with the initiation of a prostate-selective alpha antagonist: a population based cohort study . BMJ351 , h5398 ( 2015 ).
  • Rau T , WohllebenG , WuttkeHet al. CYP2D6 genotype: impact on adverse effects and nonresponse during treatment with antidepressants – a pilot study . Clin. Pharmacol. Ther.75 ( 5 ), 386 – 393 ( 2004 ).
  • Hicks JK , SangkuhlK , SwenJJet al. Clinical pharmacogenetics implementation consortium guideline (CPIC) for CYP2D6 and CYP2C19 genotypes and dosing of tricyclic antidepressants: 2016 update . Clin. Pharmacol. Ther. doi:10.1002/cpt.597 ( 2016 ) ( Epub ahead of print ).
  • Hicks JK , BishopJR , SangkuhlKet al. Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for CYP2D6 and CYP2C19 genotypes and dosing of selective serotonin reuptake inhibitors . Clin. Pharmacol. Ther.98 ( 2 ), 127 – 134 ( 2015 ).
  • Pitychoutis PM , KokrasN , SanoudouD , DallaC , Papadopoulou-DaifotiZ . Pharmacogenetic considerations for late life depression therapy . Expert Opin. Drug Metab. Toxicol.9 ( 8 ), 989 – 999 ( 2013 ).
  • Miller AH , MaleticV , RaisonCL . Inflammation and its discontents: the role of cytokines in the pathophysiology of major depression . Biol. Psychiatry65 ( 9 ), 732 – 741 ( 2009 ).
  • De Martinis M , FranceschiC , MontiD , GinaldiL . Inflammation markers predicting frailty and mortality in the elderly . Exp. Mol. Pathol.80 ( 3 ), 219 – 227 ( 2006 ).
  • Powell TR , SchalkwykLC , HeffernanALet al. Tumor necrosis factor and its targets in the inflammatory cytokine pathway are identified as putative transcriptomic biomarkers for escitalopram response . Eur. Neuropsychopharmacol.23 ( 9 ), 1105 – 1114 ( 2013 ).
  • Ferrucci L , CavazziniC , CorsiAet al. Biomarkers of frailty in older persons . J. Endocrinol. Invest.25 ( 10 Suppl. ), 10 – 15 ( 2001 ).
  • Clegg A , YoungJ , IliffeS , RikkertMO , RockwoodK . Frailty in elderly people . Lancet381 ( 9868 ), 752 – 762 ( 2013 ).
  • Spina E , De LeonJ . Metabolic drug interactions with newer antipsychotics: a comparative review . Basic Clin. Pharmacol. Toxicol.100 ( 1 ), 4 – 22 ( 2007 ).
  • Otani K , AoshimaT . Pharmacogenetics of classical and new antipsychotic drugs . Ther. Drug Monit.22 ( 1 ), 118 – 121 ( 2000 ).
  • Livezey MR , BriggsED , BollesAK , NagyLD , FujiwaraR , FurgeLL . Metoclopramide is metabolized by CYP2D6 and is a reversible inhibitor, but not inactivator, of CYP2D6 . Xenobiotica44 ( 4 ), 309 – 319 ( 2014 ).
  • Herings RM , StrickerBHC , De BoerA , BakkerA , SturmansF . Benzodiazepines and the risk of falling leading to femur fractures: dosage more important than elimination half-life . Arch. Intern. Med.155 ( 16 ), 1801 – 1807 ( 1995 ).
  • Blachman NL , LeipzigRM , MazumdarM , PoeranJ . High-risk medications in hospitalized elderly adults: are we making it easy to do the wrong thing?J. Am. Geriatr. Soc.65 ( 3 ), 603 – 607 ( 2017 ).
  • Glass J , LanctôtKL , HerrmannN , SprouleBA , BustoUE . Sedative hypnotics in older people with insomnia: meta-analysis of risks and benefits . BMJ331 ( 7526 ), 1169 ( 2005 ).
  • Wang PS , BohnRL , GlynnRJ , MogunH , AvornJ . Zolpidem use and hip fractures in older people . J. Am. Geriatr. Soc.49 ( 12 ), 1685 – 1690 ( 2001 ).
  • Fukasawa T , SuzukiA , OtaniK . Effects of genetic polymorphism of cytochrome P450 enzymes on the pharmacokinetics of benzodiazepines . J. Clin. Phar. Ther.32 ( 4 ), 333 – 341 ( 2007 ).
  • Andersson T , MinersJ , VeroneseM , BirkettD . Diazepam metabolism by human liver microsomes is mediated by both S-mephenytoin hydroxylase and CYP3A isoforms . Br. J. Clin. Pharmacol.38 ( 2 ), 131 – 137 ( 1994 ).
  • Inomata S , NagashimaA , ItagakiFet al. CYP2C19 genotype affects diazepam pharmacokinetics and emergence from general anesthesia . Clin. Pharmacol. Ther.78 ( 6 ), 647 – 655 ( 2005 ).
  • Bertilsson L , HenthornTK , SanzE , TybringG , SäweJ , VillénT . Importance of genetic factors in the regulation of diazepam metabolism: relationship to S-mephenytoin, but not debrisoquin, hydroxylation phenotype . Clin. Pharmacol. Ther.45 ( 4 ), 348 – 355 ( 1989 ).
  • Stingl J , BartelsH , VivianiR , LehmannM , BrockmöllerJ . Relevance of UDP-glucuronosyltransferase polymorphisms for drug dosing: a quantitative systematic review . Pharmacol. Ther.141 ( 1 ), 92 – 116 ( 2014 ).
  • Ham AC , ZiereG , BroerLet al. CYP2C9 genotypes modify benzodiazepine-related fall risk: original results from three studies with meta-analysis . J. Am. Med. Dir. Assoc.18 ( 1 ), 88.e81 – 88.e15 ( 2017 ).
  • Thorn CF , Whirl-CarrilloM , LeederJS , KleinTE , AltmanRB . PharmGKB summary: phenytoin pathway . Pharmacogenet. Genomics22 ( 6 ), 466 – 470 ( 2012 ).
  • Caudle KE , RettieAE , Whirl-CarrilloMet al. Clinical pharmacogenetics implementation consortium guidelines for CYP2C9 and HLA-B genotypes and phenytoin dosing . Clin. Pharmacol. Ther.96 ( 5 ), 542 – 548 ( 2014 ).
  • Klotz U . The role of pharmacogenetics in the metabolism of antiepileptic drugs . Clin. Pharmacokinet.46 ( 4 ), 271 – 279 ( 2007 ).
  • Pickering RM , GrimbergenYA , RigneyUet al. A meta-analysis of six prospective studies of falling in Parkinson’s disease . Mov. Disord.22 ( 13 ), 1892 – 1900 ( 2007 ).
  • Ashburn A , StackE , PickeringRM , WardCD . A community-dwelling sample of people with Parkinson’s disease: characteristics of fallers and non-fallers . Age Ageing30 ( 1 ), 47 – 52 ( 2001 ).
  • Vestergaard P , RejnmarkL , MosekildeL . Fracture risk associated with parkinsonism and anti-Parkinson drugs . Calcif. Tissue Int.81 ( 3 ), 153 – 161 ( 2007 ).
  • Chan A , PirmohamedM , ComabellaM . Pharmacogenomics in neurology: current state and future steps . Ann. Neurol.70 ( 5 ), 684 – 697 ( 2011 ).
  • Arbouw ME , GuchelaarH-J , EgbertsTC . Novel insights in pharmacogenetics of drug response in Parkinson’s disease . Pharmacogenomics11 ( 2 ), 127 – 129 ( 2010 ).
  • Kalinderi K , FidaniL , KatsarouZ , BostantjopoulouS . Pharmacological treatment and the prospect of pharmacogenetics in Parkinson’s disease . Int. J. Clin. Pract.65 ( 12 ), 1289 – 1294 ( 2011 ).
  • Bloem BR , GrimbergenYA , CramerM , WillemsenM , ZwindermanAH . Prospective assessment of falls in Parkinson’s disease . J. Neurol.248 ( 11 ), 950 – 958 ( 2001 ).
  • Kim DH , BrownRT , DingEL , KielDP , BerrySD . Dementia medications and risk of falls, syncope, and related adverse events: meta-analysis of randomized controlled trials . J. Am. Geriatr. Soc.59 ( 6 ), 1019 – 1031 ( 2011 ).
  • Muir SW , GopaulK , Montero OdassoMM . The role of cognitive impairment in fall risk among older adults: a systematic review and meta-analysis . Age Ageing41 ( 3 ), 299 – 308 ( 2012 ).
  • Henderson EJ , LordSR , BrodieMAet al. Rivastigmine for gait stability in patients with Parkinson’s disease (ReSPonD): a randomised, double-blind, placebo-controlled, Phase II trial . Lancet Neurol.15 ( 3 ), 249 – 258 ( 2016 ).
  • Seripa D , BizzarroA , PilottoAet al. Role of cytochrome P4502D6 functional polymorphisms in the efficacy of donepezil in patients with Alzheimer’s disease . Pharmacogenet. Genomics21 ( 4 ), 225 – 230 ( 2011 ).
  • Bachus R , BickelU , ThomsenT , RootsI , KewitzH . The O-demethylation of the antidementia drug galanthamine is catalysed by cytochrome P450 2D6 . Pharmacogenetics9 ( 6 ), 661 – 668 ( 1999 ).
  • Noetzli M , EapCB . Pharmacodynamic, pharmacokinetic and pharmacogenetic aspects of drugs used in the treatment of Alzheimer’s disease . Clin. Pharmacokinet.52 ( 4 ), 225 – 241 ( 2013 ).
  • Stubbs B , SchofieldP , BinnekadeT , PatchayS , SepehryA , EggermontL . Pain is associated with recurrent falls in community-dwelling older adults: evidence from a systematic review and meta-analysis . Pain Med.15 ( 7 ), 1115 – 1128 ( 2014 ).
  • Eggermont LH , LeveilleSG , ShiLet al. Pain characteristics associated with the onset of disability in older adults: the maintenance of balance, independent living, intellect, and zest in the Elderly Boston Study . J. Am. Geriatr. Soc.62 ( 6 ), 1007 – 1016 ( 2014 ).
  • Patel KV , PhelanEA , LeveilleSGet al. High prevalence of falls, fear of falling, and impaired balance in older adults with pain in the United States: findings from the 2011 National Health and Aging Trends Study . J. Am. Geriatr. Soc.62 ( 10 ), 1844 – 1852 ( 2014 ).
  • Rolita L , SpegmanA , TangX , CronsteinBN . Greater number of narcotic analgesic prescriptions for osteoarthritis is associated with falls and fractures in elderly adults . J. Am. Geriatr. Soc.61 ( 3 ), 335 – 340 ( 2013 ).
  • Buckeridge D , HuangA , HanleyJet al. Risk of injury associated with opioid use in older adults . J. Am. Geriatr. Soc.58 ( 9 ), 1664 – 1670 ( 2010 ).
  • Madadi P , AmstutzU , RiederMet al. Clinical practice guideline: CYP2D6 genotyping for safe and efficacious codeine therapy . J. Popul. Ther. Clin. Pharmacol.20 ( 3 ), e369 – e396 ( 2013 ).
  • Crews KR , GaedigkA , DunnenbergerHMet al. Clinical Pharmacogenetics Implementation Consortium guidelines for cytochrome P450 2D6 genotype and codeine therapy: 2014 update . Clin. Pharmacol. Ther.95 ( 4 ), 376 – 382 ( 2014 ).
  • Hegeman J , Van Den BemtBJ , DuysensJ , Van LimbeekJ . NSAIDs and the risk of accidental falls in the elderly . Drug Saf.32 ( 6 ), 489 – 498 ( 2009 ).
  • Kirchheiner J , BrockmöllerJ . Clinical consequences of cytochrome P450 2C9 polymorphisms . Clin. Pharmacol. Ther.77 ( 1 ), 1 – 16 ( 2005 ).
  • Schmitz G , AslanidisC , LacknerKJ . Pharmacogenomics: implications for laboratory medicine . Clin. Chim. Acta308 ( 1 ), 43 – 53 ( 2001 ).
  • Toornvliet R , Van BerckelBN , LuurtsemaGet al. Effect of age on functional P-glycoprotein in the blood-brain barrier measured by use of (R)-[(11)C]verapamil and positron emission tomography . Clin. Pharmacol. Ther.79 ( 6 ), 540 – 548 ( 2006 ).
  • Hoffmeyer S , BurkO , Von RichterOet al. Functional polymorphisms of the human multidrug-resistance gene: multiple sequence variations and correlation of one allele with P-glycoprotein expression and activity in vivo . Proc. Natl Acad. Sci. USA97 ( 7 ), 3473 – 3478 ( 2000 ).
  • Group TSR . A randomized trial of intensive versus standard blood-pressure control . N. Engl. J. Med.373 ( 22 ), 2103 – 2116 ( 2015 ).
  • Tinetti ME , HanL , LeeDSet al. Antihypertensive medications and serious fall injuries in a nationally representative sample of older adults . JAMA Intern. Med.174 ( 4 ), 588 – 595 ( 2014 ).
  • Gangavati A , HajjarI , QuachLet al. Hypertension, orthostatic hypotension, and the risk of falls in a community-dwelling elderly population: the maintenance of balance, independent living, intellect, and zest in the Elderly of Boston Study . J. Am. Geriatr. Soc.59 ( 3 ), 383 – 389 ( 2011 ).
  • Blake CM , KharaschE , SchwabM , NageleP . Meta-analysis of CYP2D6 metabolizer phenotype and metoprolol pharmacokinetics . Clin. Pharmacol. Ther.94 ( 3 ), 394 – 399 ( 2013 ).
  • Sehrt D , MeinekeI , TzvetkovM , GultepeS , BrockmollerJ . Carvedilol pharmacokinetics and pharmacodynamics in relation to CYP2D6 and ADRB pharmacogenetics . Pharmacogenomics12 ( 6 ), 783 – 795 ( 2011 ).
  • Chiba Y , KimbaraY , KoderaRet al. Risk factors associated with falls in elderly patients with Type 2 diabetes . J. Diabetes Complications29 ( 7 ), 898 – 902 ( 2015 ).
  • Nelson JM , DufrauxK , CookPF . The relationship between glycemic control and falls in older adults . J. Am. Geriatr. Soc.55 ( 12 ), 2041 – 2044 ( 2007 ).
  • Becker M , VisserL , TrienekensP , HofmanA , SchaikR , StrickerB . Cytochrome P450 2C9 *2 and *3 polymorphisms and the dose and effect of sulfonylurea in Type II diabetes mellitus . Clin. Pharmacol. Ther.83 ( 2 ), 288 – 292 ( 2008 ).
  • Kirchheiner J , RootsI , GoldammerM , RosenkranzB , BrockmöllerJ . Effect of genetic polymorphisms in cytochrome P450 (CYP) 2C9 and CYP2C8 on the pharmacokinetics of oral antidiabetic drugs . Clin. Pharmacokinet.44 ( 12 ), 1209 – 1225 ( 2012 ).
  • Holstein A , PlaschkeA , PtakMet al. Association between CYP2C9 slow metabolizer genotypes and severe hypoglycaemia on medication with sulphonylurea hypoglycaemic agents . Br. J. Clin. Pharmacol.60 ( 1 ), 103 – 106 ( 2005 ).
  • Bodmer M , MeierC , KrähenbühlS , JickSS , MeierCR . Metformin, sulfonylureas, or other antidiabetes drugs and the risk of lactic acidosis or hypoglycemia A nested case–control analysis . Diabetes Care31 ( 11 ), 2086 – 2091 ( 2008 ).
  • Gude D . Red carpeting the newer antidiabetics . J. Pharmacol. Pharmacother.3 ( 2 ), 127 – 131 ( 2012 ).
  • Wang Z , XiangQ , CuiY , ZhaoX , ZhouY . The influence of UGT2B7, UGT1A8, MDR1, ALDH, ADH, CYP3A4 and CYP3A5 genetic polymorphisms on the pharmacokinetics of silodosin in healthy Chinese volunteers . Drug Metab. Pharmacokinet.28 ( 3 ), 239 – 243 ( 2013 ).
  • Paulzen M , FinkelmeyerA , GrozingerM . Augmentative effects of fluvoxamine on duloxetine plasma levels in depressed patients . Pharmacopsychiatry44 ( 7 ), 317 – 323 ( 2011 ).
  • Gardiner SJ , BeggEJ . Pharmacogenetics, drug-metabolizing enzymes, and clinical practice . Pharmacol. Rev.58 ( 3 ), 521 – 590 ( 2006 ).
  • Klieber M , OberacherH , HofstaetterSet al. CYP2C19 phenoconversion by routinely prescribed proton pump inhibitors Omeprazole and Esomeprazole: clinical implications for personalized medicine . J. Pharmacol. Exp. Ther.354 ( 3 ), 426 – 430 ( 2015 ).
  • Preskorn SH , KaneCP , LobelloKet al. Cytochrome P450 2D6 phenoconversion is common in patients being treated for depression: implications for personalized medicine . J. Clin. Psychiatry74 ( 6 ), 614 – 621 ( 2013 ).
  • Shah RR , SmithRL . Addressing phenoconversion: the Achilles’ heel of personalized medicine . Br. J. Clin. Pharmacol.79 ( 2 ), 222 – 240 ( 2015 ).
  • Richardson K , BennettK , KennyRA . Polypharmacy including falls risk-increasing medications and subsequent falls in community-dwelling middle-aged and older adults . Age Ageing44 ( 1 ), 90 – 96 ( 2015 ).
  • Stingl Kirchheiner JC , BrockmollerJ . Why, when, and how should pharmacogenetics be applied in clinical studies? current and future approaches to study designs . Clin. Pharmacol. Ther.89 ( 2 ), 198 – 209 ( 2011 ).
  • Ishizawa Y , Yasui-FurukoriN , TakahataT , SasakiM , TateishiT . The effect of aging on the relationship between the cytochrome P450 2C19 genotype and omeprazole pharmacokinetics . Clin. Pharmacokinet.44 ( 11 ), 1179 – 1189 ( 2005 ).

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