Abstract
Over 1000 new molecular entities (NMEs) have been introduced into the marketplace since the end of World War II. These therapeutic innovations have contributed to an increase in life expectancy but have also increased the prevalence of polypharmacy and the risk for adverse drug-drug interactions. The economic burden associated with adverse drug events is estimated to exceed $100 billion in the United States alone. These adverse events are most often associated with chronic medications used to manage hypercholesterolemia, diabetes, asthma, and depression that are widely prescribed in more economically developed countries. Acute infections most often lead to the short-term prescription of antimicrobials that can increase the risk for adverse events and or therapeutic failure when co-prescribed with these agents. Likewise combination antimicrobial therapies used to manage chronic or deep-seated infections carry a high potential for drug-drug interactions. The large number of NMEs and continued influx of new agents limits the design of a comprehensive resource that can accurately predict the extent and clinical implications of pharmacokinetic and pharmacodynamic interactions. This chapter provides a broad overview of clinical pharmacology from the perspective of systems that influence absorption, distribution, metabolism, and excretion of drugs that can lead to pharmacokinetic drug interactions.
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References
Roe S, Long R, King K (2016) Pharmacies miss half of dangerous drug combinations. Chicago Tribune, Chicago. Available from http://www.chicagotribune.com/news/watchdog/druginteractions/ct-drug-interactions-pharmacy-met-20161214-story.html. Accessed 15 Oct 2017
Long R, Roe S (2017) Illinois’ new pharmacy rules to improve consumer safety may start today. Chicago Tribune, Chicago. Available from http://www.chicagotribune.com/news/watchdog/druginteractions/ct-drug-interactions-rauner-rules-met-20170818-story.html. Accessed 15 Oct 2017
Wang Y, Eldridge N, Metersky ML, Verzier NR, Meehan TP, Pandolfi MM et al (2014) National trends in patient safety for four common conditions, 2005-2011. N Engl J Med 370(4):341–351
Qato DM, Wilder J, Schumm LP, Gillet V, Alexander GC (2016) Changes in prescription and over-the-counter medication and dietary supplement use among older adults in the United States, 2005 vs 2011. JAMA Intern Med 176:473–482
U.S. Department of Health and Human Services, Office of Disease Prevention and Health Promotion (2014) National action plan for adverse drug event prevention. Author, Washington, DC
Plank-Kiegele B, Burkle T, Muller F, Patapovas A, Sonst A, Pfistermeister B et al (2017) Data requirements for the correct identification of medication errors and adverse drug events in patients presenting at an emergency department. Methods Inf Med 56(4):276–282
Johnson JA, Bootman JL (1995) Drug-related morbidity and mortality. A cost-of-illness model. Arch Intern Med 155(18):1949–1956
Chen F, Hu ZY, Jia WW, Lu JT, Zhao YS (2014) Quantitative evaluation of drug-drug interaction potentials by in vivo information- guided prediction approach. Curr Drug Metab 15(8):761–766
Varma MV, Pang KS, Isoherranen N, Zhao P (2015) Dealing with the complex drug-drug interactions: towards mechanistic models. Biopharm Drug Dispos 36(2):71–92
Rinner C, Grossmann W, Sauter SK, Wolzt M, Gall W (2015) Effects of shared electronic health record systems on drug-drug interaction and duplication warning detection. Biomed Res Int 2015:380497
Kinch MS, Haynesworth A, Kinch SL, Hoyer D (2014) An overview of FDA-approved new molecular entities: 1827-2013. Drug Discov Today 19(8):1033–1039
Fung KW, Kapusnik-Uner J, Cunningham J, Higby-Baker S, Bodenreider O (2017) Comparison of three commercial knowledge bases for detection of drug-drug interactions in clinical decision support. J Am Med Inform Assoc 24(4):806–812
De Clercq E, Li G (2016) Approved antiviral drugs over the past 50 years. Clin Microbiol Rev 29(3):695–747
Seiple IB, Zhang Z, Jakubec P, Langlois-Mercier A, Wright PM, Hog DT et al (2016) A platform for the discovery of new macrolide antibiotics. Nature 533(7603):338–345
Yan M, Baran PS (2016) Drug discovery: fighting evolution with chemical synthesis. Nature 533(7603):326–327
Pai MP, Bertino JS Jr (2014) Tables of antimicrobial agent pharmacology. In: Mandell GLBJ, Dolin RL, Blaser M (eds) Principles and practice of infectious diseases, 8th edn. Elsevier, Philadelphia, PA, USA
Silver LL (2011) Challenges of antibacterial discovery. Clin Microbiol Rev 24(1):71–109
Mudie DM, Amidon GL, Amidon GE (2010) Physiological parameters for oral delivery and in vitro testing. Mol Pharm 7(5):1388–1405
Al-Kassas R, Bansal M, Shaw J (2017) Nanosizing techniques for improving bioavailability of drugs. J Control Release 260:202–212
Tatro DS (1972) Tetracycline-antacid interactions. JAMA 220(4):586
Ogawa R, Echizen H (2011) Clinically significant drug interactions with antacids: an update. Drugs 71(14):1839–1864
Laksitorini M, Prasasty VD, Kiptoo PK, Siahaan TJ (2014) Pathways and progress in improving drug delivery through the intestinal mucosa and blood-brain barriers. Ther Deliv 5(10):1143–1163
Linnankoski J, Makela J, Palmgren J, Mauriala T, Vedin C, Ungell AL et al (2010) Paracellular porosity and pore size of the human intestinal epithelium in tissue and cell culture models. J Pharm Sci 99(4):2166–2175
Matsson P, Doak BC, Over B, Kihlberg J (2016) Cell permeability beyond the rule of 5. Adv Drug Deliv Rev 101:42–61
van Waterschoot RA, Schinkel AH (2011) A critical analysis of the interplay between cytochrome P450 3A and P-glycoprotein: recent insights from knockout and transgenic mice. Pharmacol Rev 63(2):390–410
Caldwell J, Gardner I, Swales N (1995) An introduction to drug disposition: the basic principles of absorption, distribution, metabolism, and excretion. Toxicol Pathol 23(2):102–114
Benet LZ, Izumi T, Zhang Y, Silverman JA, Wacher VJ (1999) Intestinal MDR transport proteins and P-450 enzymes as barriers to oral drug delivery. J Control Release 62(1–2):25–31
Yang B, Smith DE (2013) Significance of peptide transporter 1 in the intestinal permeability of valacyclovir in wild-type and PepT1 knockout mice. Drug Metab Dispos 41(3):608–614
Biegel A, Gebauer S, Hartrodt B, Brandsch M, Neubert K, Thondorf I (2005) Three-dimensional quantitative structure-activity relationship analyses of beta-lactam antibiotics and tripeptides as substrates of the mammalian H+/peptide cotransporter PEPT1. J Med Chem 48(13):4410–4419
Sarin H (2010) Physiologic upper limits of pore size of different blood capillary types and another perspective on the dual pore theory of microvascular permeability. J Angiogenes Res 2:14
Schafer M, Schneider TR, Sheldrick GM (1996) Crystal structure of vancomycin. Structure 4(12):1509–1515
Li MW, Mruk DD, Cheng CY (2012) Gap junctions and blood-tissue barriers. Adv Exp Med Biol 763:260–280
Smith DA, Di L, Kerns EH (2010) The effect of plasma protein binding on in vivo efficacy: misconceptions in drug discovery. Nat Rev Drug Discov 9(12):929–939
Fischman AJ, Alpert NM, Livni E, Ray S, Sinclair I, Callahan RJ et al (1993) Pharmacokinetics of 18F-labeled fluconazole in healthy human subjects by positron emission tomography. Antimicrob Agents Chemother 37(6):1270–1277
Debruyne D (1997) Clinical pharmacokinetics of fluconazole in superficial and systemic mycoses. Clin Pharmacokinet 33(1):52–77
McElnay JC, D’Arcy PF (1983) Protein binding displacement interactions and their clinical importance. Drugs 25(5):495–513
Toutain PL, Bousquet-Melou A (2004) Volumes of distribution. J Vet Pharmacol Ther 27(6):441–453
Hamilton JA (1989) Medium-chain fatty acid binding to albumin and transfer to phospholipid bilayers. Proc Natl Acad Sci U S A 86(8):2663–2667
Manallack DT, Prankerd RJ, Yuriev E, Oprea TI, Chalmers DK (2013) The significance of acid/base properties in drug discovery. Chem Soc Rev 42(2):485–496
Obach RS, Lombardo F, Waters NJ (2008) Trend analysis of a database of intravenous pharmacokinetic parameters in humans for 670 drug compounds. Drug Metab Dispos 36(7):1385–1405
Smith DA, Beaumont K, Maurer TS, Di L (2015) Volume of distribution in drug design. J Med Chem 58(15):5691–5698
Grover A, Benet LZ (2009) Effects of drug transporters on volume of distribution. AAPS J 11(2):250–261
Santucci R, Fothergill H, Laugel V, Perville A, De Saint Martin A, Gerout AC et al (2010) The onset of acute oxcarbazepine toxicity related to prescription of clarithromycin in a child with refractory epilepsy. Br J Clin Pharmacol 69(3):314–316
Ruggiero A, Villa CH, Bander E, Rey DA, Bergkvist M, Batt CA et al (2010) Paradoxical glomerular filtration of carbon nanotubes. Proc Natl Acad Sci U S A 107(27):12369–12374
Fagerholm U (2007) Prediction of human pharmacokinetics - renal metabolic and excretion clearance. J Pharm Pharmacol 59(11):1463–1471
Brodie BB, Axelrod J, Cooper JR, Gaudette L, La Du BN, Mitoma C et al (1955) Detoxication of drugs and other foreign compounds by liver microsomes. Science 121(3147):603–604
Charifson PS, Walters WP (2014) Acidic and basic drugs in medicinal chemistry: a perspective. J Med Chem 57(23):9701–9717
Zanger UM, Schwab M (2013) Cytochrome P450 enzymes in drug metabolism: regulation of gene expression, enzyme activities, and impact of genetic variation. Pharmacol Ther 138(1):103–141
Ohkura K, Kawaguchi Y, Watanabe Y, Masubuchi Y, Shinohara Y, Hori H (2009) Flexible structure of cytochrome P450: promiscuity of ligand binding in the CYP3A4 heme pocket. Anticancer Res 29(3):935–942
Coughtrie MW (2015) Ontogeny of human conjugating enzymes. Drug Metab Lett 9(2):99–108
Reith D, Medlicott NJ, Kumara De Silva R, Yang L, Hickling J, Zacharias M (2009) Simultaneous modelling of the Michaelis-Menten kinetics of paracetamol sulphation and glucuronidation. Clin Exp Pharmacol Physiol 36(1):35–42
Walker K, Ginsberg G, Hattis D, Johns DO, Guyton KZ, Sonawane B (2009) Genetic polymorphism in N-Acetyltransferase [NAT]: population distribution of NAT1 and NAT2 activity. J Toxicol Environ Health B Crit Rev 12(5–6):440–472
Nelson E (1964) Kinetics of the acetylation and excretion of sulfonamides and a comparison of two models. Antibiot Chemother 12:29–40
Stettner M, Steinberger D, Hartmann CJ, Pabst T, Konta L, Hartung HP et al (2015) Isoniazid-induced polyneuropathy in a tuberculosis patient - implication for individual risk stratification with genotyping? Brain Behav 5(8):e00326
Masereeuw R, Russel FG (2001) Mechanisms and clinical implications of renal drug excretion. Drug Metab Rev 33(3–4):299–351
Barger AC, Herd JA (1971) The renal circulation. N Engl J Med 284(9):482–490
Ivanyuk A, Livio F, Biollaz J, Buclin T (2017) Renal drug transporters and drug interactions. Clin Pharmacokinet 56(8):825–892
Werko L, Ek J, Varnauskas E, Bucht H, Thomasson B, Eliasch H (1955) The relationship between renal blood flow, glomerular filtration rate and sodium excretion, cardiac output and pulmonary and systemic blood pressures in various heart disorders. Am Heart J 49(6):823–837
Pai MP, Norenberg JP, Telepak RA, Sidney DS, Yang S (2005) Assessment of effective renal plasma flow, enzymuria, and cytokine release in healthy volunteers receiving a single dose of amphotericin B desoxycholate. Antimicrob Agents Chemother 49(9):3784–3788
Burnell JM, Kirby WM (1951) Effectiveness of a new compound, benemid, in elevating serum penicillin concentrations. J Clin Invest 30(7):697–700
Tanigawara Y (2000) Role of P-glycoprotein in drug disposition. Ther Drug Monit 22(1):137–140
Klaassen CD, Cui JY (2015) Review: aechanisms of how the intestinal microbiota alters the effects of drugs and bile acids. Drug Metab Dispos 43(10):1505–1521
Zhanel GG, Siemens S, Slayter K, Mandell L (1999) Antibiotic and oral contraceptive drug interactions: is there a need for concern? Can J Infect Dis 10(6):429–433
U.S. Department of Health and Human Services, U.S. Food and Drug Administration (2015) Drug interactions & labeling. Washington, DC. Available from https://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/DrugInteractionsLabeling/default.htm. Accessed 15 Oct 2017
Jankovic SM (2014) Comparison of EMA and FDA guidelines for drug interactions: an overview. Clin Res Regul Aff 31:29–34
Prucksaritanont T, Chu X, Gibson C, Cui D, Yee KL, Ballard J, Cabalu T, Hochman J (2013) Drug-drug interaction studies: regulatory guidance and an industry perspective. AAPS Journal 15:629–645
Nagai N (2010) Drug interaction studies on new drug applications: current situations and regulatory views in Japan. Drug Metab Pharmacokinet 25(1):3–15
Zhang L, Zhang YD, Zhao P, Huang SM (2009) Predicting drug-drug interactions: an FDA perspective. AAPS J 11(2):300–306
Fowler S, Zhang H (2008) In vitro evaluation of reversible and irreversible cytochrome P450 inhibition: current status on methodologies and their utility for predicting drug-drug interactions. AAPS J 10(2):410–424
Huang SM, Strong JM, Zhang L, Reynolds KS, Nallani S, Temple R et al (2008) New era in drug interaction evaluation: US food and drug administration update on CYP enzymes, transporters, and the guidance process. J Clin Pharmacol 48(6):662–670
de Andres F, LL A (2016) Simultaneous determination of cytochrome P450 oxidation capacity in humans: a review on the phenotyping cocktail approach. Curr Pharm Biotechnol 17(13):1159–1180
U.S. Department of Health and Human Services, U.S. Food and Drug Administration (2015) Drug interactions & labeling. Washington, DC. Available from https://www.accessdata.fda.gov/scripts/cder/daf/. Accessed 15 Oct 2017
Patel RI, Beckett RD (2016) Evaluation of resources for analyzing drug interactions. J Med Libr Assoc 104(4):290–295
Liu S, Tang B, Chen Q, Wang X (2016) Drug-drug interaction extraction via convolutional neural networks. Comput Math Methods Med 2016:6918381
Ayvaz S, Horn J, Hassanzadeh O, Zhu Q, Stan J, Tatonetti NP et al (2015) Toward a complete dataset of drug-drug interaction information from publicly available sources. J Biomed Inform 55:206–217
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Pai, M.P., Kiser, J.J., Gubbins, P.O., Rodvold, K.A. (2018). Introduction to Drug-Drug Interactions. In: Pai, M., Kiser, J., Gubbins, P., Rodvold, K. (eds) Drug Interactions in Infectious Diseases: Mechanisms and Models of Drug Interactions. Infectious Disease. Humana Press, Cham. https://doi.org/10.1007/978-3-319-72422-5_1
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