Ebook Translational admet for drug therapy - Principles, methods, and pharmaceutical applications: Part 2
➤ Gửi thông báo lỗi ⚠️ Báo cáo tài liệu vi phạmNội dung chi tiết: Ebook Translational admet for drug therapy - Principles, methods, and pharmaceutical applications: Part 2
Ebook Translational admet for drug therapy - Principles, methods, and pharmaceutical applications: Part 2
5DRUG-DRUG INTERACTION: FROMBENCH TO DRUG LABEL5.1INTRODUCTION: THE IMPACT OF DRUG-DRUG INTERACTION ON DRUG DISPOSITION AND DRUG SAFETYDrug-drug inter Ebook Translational admet for drug therapy - Principles, methods, and pharmaceutical applications: Part 2raction (DDI) is one of the major obstacles for the pharmaceutical drug development process: uncovering its potential on any adverse clinical outcomes becomes increasingly important in drug discovery and development. Both in vitro and in vivo precl inical investigations to assess the any clinical ou Ebook Translational admet for drug therapy - Principles, methods, and pharmaceutical applications: Part 2tcomes prior to drug launch are taken into account to reveal the potential of DD1 and its mechanism of any drug under development. Evaluation of the pEbook Translational admet for drug therapy - Principles, methods, and pharmaceutical applications: Part 2
ossible interactions of a drug candidate with other drugs as soon as possible—not only as an inhibitor or inducer (perpetrator) but also as a substrat5DRUG-DRUG INTERACTION: FROMBENCH TO DRUG LABEL5.1INTRODUCTION: THE IMPACT OF DRUG-DRUG INTERACTION ON DRUG DISPOSITION AND DRUG SAFETYDrug-drug inter Ebook Translational admet for drug therapy - Principles, methods, and pharmaceutical applications: Part 2ently their evaluation is critical to studies within all the drug development stages, drug discovery, and regulation of new drug candidates to avoid any serious toxicity that leads to drug withdrawal postmarket. Finally, the ultimate goal of non-clinical and clinical DD1 studies is to permit integra Ebook Translational admet for drug therapy - Principles, methods, and pharmaceutical applications: Part 2tion of DDI knowledge acquired in the development phase into prescribing guidance in a manner that enables optimal postmarketing risk management folloEbook Translational admet for drug therapy - Principles, methods, and pharmaceutical applications: Part 2
wing marketing authorization.Not all the preclinically determined DDls can be considered as clinically significant (poor correlation between in vitro 5DRUG-DRUG INTERACTION: FROMBENCH TO DRUG LABEL5.1INTRODUCTION: THE IMPACT OF DRUG-DRUG INTERACTION ON DRUG DISPOSITION AND DRUG SAFETYDrug-drug inter Ebook Translational admet for drug therapy - Principles, methods, and pharmaceutical applications: Part 2n B. Yanni.Ỡ 2015 John Wiley & Sons. Inc. Published 2015 by John Wiley & Sons. Inc.140DRUG-DRUG INTERACTION: FROM BENCH TO DRUG LABELFigure 5.1 Effect of DDI on the disposition of victim target drug.concentrations of victim/object drug and its perpetrator play a major role in causing effective inter Ebook Translational admet for drug therapy - Principles, methods, and pharmaceutical applications: Part 2action, and alteration of drug concentrations will lead to diminishing the DDI potential. On the other hand. DD1 can result in altering the therapeutiEbook Translational admet for drug therapy - Principles, methods, and pharmaceutical applications: Part 2
c effect, or sometimes altering the toxic effects of a medication by administration with another drug. As shown in Figure 5.1. inhibition or induction5DRUG-DRUG INTERACTION: FROMBENCH TO DRUG LABEL5.1INTRODUCTION: THE IMPACT OF DRUG-DRUG INTERACTION ON DRUG DISPOSITION AND DRUG SAFETYDrug-drug inter Ebook Translational admet for drug therapy - Principles, methods, and pharmaceutical applications: Part 2s and potential effects on efficacy and/or safely of the victim drug. Such DDIs are classified as pharmacokinetics (PK) interactions. There are other types of interactions, such as pharmacodynamics (PD) interactions that occur when one drug alters the pharmacologic effect (efficacy and/or safely) of Ebook Translational admet for drug therapy - Principles, methods, and pharmaceutical applications: Part 2 another coadministered drug without affecting its PK.Historically, the impact of DD1 on drug disposition and safety was reported in several drug therEbook Translational admet for drug therapy - Principles, methods, and pharmaceutical applications: Part 2
apy programs during the last decade where [inadequate ĐĐI evaluation of drug candidates resulted in postmarketing withdrawal after drug approval [ I J5DRUG-DRUG INTERACTION: FROMBENCH TO DRUG LABEL5.1INTRODUCTION: THE IMPACT OF DRUG-DRUG INTERACTION ON DRUG DISPOSITION AND DRUG SAFETYDrug-drug inter Ebook Translational admet for drug therapy - Principles, methods, and pharmaceutical applications: Part 2 fatal interactions with sensitive substrates of P450 3A (CYP3A), such as the calcium channel blocker felodipine due to its absorption, distribution, metabolism, and excretion (ADME) profile as a strong mechanism-based inactivator of CYP3A and an inhibitor of the efflux transporter p-gly coprote in Ebook Translational admet for drug therapy - Principles, methods, and pharmaceutical applications: Part 2(p-gp). Mibefradil was voluntarily withdrawn in June 1998 within a year following approval, after United Slates Prescribing Information (ƯSPI) recommeEbook Translational admet for drug therapy - Principles, methods, and pharmaceutical applications: Part 2
nded the need to administer the drug in concomitant use of 26 drugs. The overall benefit/risk ratio for mibefradil was unfavorable, as other therapeut5DRUG-DRUG INTERACTION: FROMBENCH TO DRUG LABEL5.1INTRODUCTION: THE IMPACT OF DRUG-DRUG INTERACTION ON DRUG DISPOSITION AND DRUG SAFETYDrug-drug inter Ebook Translational admet for drug therapy - Principles, methods, and pharmaceutical applications: Part 2stigation toDDLS IMPLICATED WITH DRUG-METABOLIZING ENZYMES (DMES)141produce DDIs with coadministered agents via effects on their PK (e.g., via metabolic inhibilion/induction by other drugs).Similarly, there are a few examples worth mentioning, such as the prokinetic agent cisapride, which was used f Ebook Translational admet for drug therapy - Principles, methods, and pharmaceutical applications: Part 2or the management of gastroesophageal retlux disease, and the antihistamine drugs terfenadine and astemizole, which are inhibitors of the ion channelEbook Translational admet for drug therapy - Principles, methods, and pharmaceutical applications: Part 2
hERG and play a critical role in cardiac repolarization. These three drugs were cleared almost exclusively via metabolism by CYP3A. With coadministrat5DRUG-DRUG INTERACTION: FROMBENCH TO DRUG LABEL5.1INTRODUCTION: THE IMPACT OF DRUG-DRUG INTERACTION ON DRUG DISPOSITION AND DRUG SAFETYDrug-drug inter Ebook Translational admet for drug therapy - Principles, methods, and pharmaceutical applications: Part 2ia torsades de pointes of these drugs clinically if they arc coadministered with many common therapeutic agents, including antibiotics such as erythromycin and consumer products such as grapefruit juice.This set of examples illustrates the importance of an adequate level of premarketing characteriza Ebook Translational admet for drug therapy - Principles, methods, and pharmaceutical applications: Part 2tion of DD1 risk, thus identifying the safety profile relative to the therapeutic index [2].5.2DDIS IMPLICATED WITH DRUG-METABOLIZING ENZYMES (DMES) AEbook Translational admet for drug therapy - Principles, methods, and pharmaceutical applications: Part 2
ND DRUG METABOLISM5.2.1 DDI Mediated by P450 InhibitionAs mentioned earlier, the PK DDI can occur when one drug alters the metabolism, by inhibition o5DRUG-DRUG INTERACTION: FROMBENCH TO DRUG LABEL5.1INTRODUCTION: THE IMPACT OF DRUG-DRUG INTERACTION ON DRUG DISPOSITION AND DRUG SAFETYDrug-drug inter Ebook Translational admet for drug therapy - Principles, methods, and pharmaceutical applications: Part 2 the P450 enzymes. by inhibition with concomitant drug treatment leading to serious clinical DDI such as those cases briefly described above. Although P450 inhibitions are implicated in the majority of clinically relevant DDIs [3.4]. there have been a few incidents of DD1 with conjugated enzymes, as Ebook Translational admet for drug therapy - Principles, methods, and pharmaceutical applications: Part 2 will be briefly mentioned below.In a clinic setting, DDI mediated by P450 inhibition was observed by the increase of plasma concentrations of victimEbook Translational admet for drug therapy - Principles, methods, and pharmaceutical applications: Part 2
drugs when coadministrated with a potent inhibitor (perpetrator), as indicated in Figure 5.1. When ketoconazole, a potent CYP3A4 inhibitor, was admini5DRUG-DRUG INTERACTION: FROMBENCH TO DRUG LABEL5.1INTRODUCTION: THE IMPACT OF DRUG-DRUG INTERACTION ON DRUG DISPOSITION AND DRUG SAFETYDrug-drug inter Ebook Translational admet for drug therapy - Principles, methods, and pharmaceutical applications: Part 2se adjustment, serious drug monitoring, or sometimes drug development termination of investigational drugs, especially when they involve a drug that has a narrow therapeutic range, such as warfarin, resulting in an increase in plasma concentration. Inadequate DDI investigations during late discovery Ebook Translational admet for drug therapy - Principles, methods, and pharmaceutical applications: Part 2 or early drug development may result in overdrug exposure, and hence unwanted toxicity in some patients when the metabolism-mediated drug eliminationEbook Translational admet for drug therapy - Principles, methods, and pharmaceutical applications: Part 2
is diminished by coadministrated inhibitor. A classic example of a drug interaction is with the antihistamine Seldane. (terfenadine) and the common a5DRUG-DRUG INTERACTION: FROMBENCH TO DRUG LABEL5.1INTRODUCTION: THE IMPACT OF DRUG-DRUG INTERACTION ON DRUG DISPOSITION AND DRUG SAFETYDrug-drug inter Ebook Translational admet for drug therapy - Principles, methods, and pharmaceutical applications: Part 2lerfenadine was accumulated to extensive toxic blood levels and to a potentially fatal arrhythmia. The case resulted142DRUG-DRUG INTERACTION: FROM BENCH TO DRUG LABELin a recall of Scldanc..by the Food and Drug Administration (FDA) and recommendation that DDI investigations be assessed relatively ea Ebook Translational admet for drug therapy - Principles, methods, and pharmaceutical applications: Part 2rly in drug development. Similarly, as mentioned earlier, mibcfradil caused serious DDI with simvastatin and with |3-blockers [7.81. Subsequently, mibEbook Translational admet for drug therapy - Principles, methods, and pharmaceutical applications: Part 2
efradil was found to be a potent inhibitor of CYP3A4. CYP2D6. and P-gp and a potent time-dependent inhibitor (TDI) for CYP3A4/3A5 [9-111- These seriou5DRUG-DRUG INTERACTION: FROMBENCH TO DRUG LABEL5.1INTRODUCTION: THE IMPACT OF DRUG-DRUG INTERACTION ON DRUG DISPOSITION AND DRUG SAFETYDrug-drug inter Ebook Translational admet for drug therapy - Principles, methods, and pharmaceutical applications: Part 2adil was withdrawn from the market a year after launch. Although CYP3A4-mediated DDI was responsible for several clinically relevant DDI and drug withdrawal, other P450 enzymes were also responsible for serious DDIs. One example is the recent withdrawal of rofecoxib. a cyclooxygenase-2-seleclive non Ebook Translational admet for drug therapy - Principles, methods, and pharmaceutical applications: Part 2steroidal anti-inflammatory drug (NSA1D), in 2006. It caused moderate increased plasma concentrations of theophylline [121 and R-warfarin [ 131. the eEbook Translational admet for drug therapy - Principles, methods, and pharmaceutical applications: Part 2
ffect implicated in some cardiovascular events in treated patients. Similarly, rofecoxib increased the plasma concentration of tizanidine more than 105DRUG-DRUG INTERACTION: FROMBENCH TO DRUG LABEL5.1INTRODUCTION: THE IMPACT OF DRUG-DRUG INTERACTION ON DRUG DISPOSITION AND DRUG SAFETYDrug-drug inter Ebook Translational admet for drug therapy - Principles, methods, and pharmaceutical applications: Part 2bition of a drug candidate can be assessed in two steps: (I) by using in vitro models and methodologies to estimate the potency of inhibition, and (2) by translating the in vitro information to clinical pharmacology investigation and determining the correlation and magnitude of interaction.5.2.1. Ỉ Ebook Translational admet for drug therapy - Principles, methods, and pharmaceutical applications: Part 2hl Vitro P450 inhibition Models and Methodologies The in vitro models, methodologies, strategies, and data interpretation to assess the potential inhiEbook Translational admet for drug therapy - Principles, methods, and pharmaceutical applications: Part 2
bition of P450 activity by investigational drug candidate have been well established now to permit their routine integration into preclinical to cliniGọi ngay
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