Biopharmaceutics. Группа авторов. Читать онлайн. Newlib. NEWLIB.NET

Автор: Группа авторов
Издательство: John Wiley & Sons Limited
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Жанр произведения: Медицина
Год издания: 0
isbn: 9781119678373
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This office is responsible for the generation, implementation and review of biopharmaceutics‐related guidance, policies and practices. There are several biopharmaceutics specific FDA regulatory guidance papers issues that are critical to the approval of new drugs. Similar to the USA there are many global regulatory bodies where biopharmaceutics guidance has been issued including the EMA (European Medicines Agency) and the Japanese Food and Drug Administration. Recently the ICH M9 guidance has sought to align these where possible for the BCS classification.

      Biopharmaceutics is an important scientific discipline, particularly for those developing new drugs. An understanding of biopharmaceutics aids in the design of appropriate drug candidates (Chapter 7) as well as optimised drug products (Chapter 8) to ensure that the drug is well absorbed from the site of administration. Clinical testing of drugs, from phase 1 to phase 4 clinical trials is expensive and time‐consuming. Biopharmaceutics tests and knowledge are critical to de‐risk changes in the clinical performance as a result of minor changes in the product and process used to manufacture the drug product used within these clinical trials. There is a strong relationship between biopharmaceutics and regulatory science during the development of drug products.

Schematic illustration of an overview of biopharmaceutics input in the drug development pathway.

      Biopharmaceutics is a relatively new science that brings together knowledge on anatomy and physiology to understand the biological environment where drugs are absorbed with materials science to appreciate the drug and excipient related effects on these processes. This book brings together the knowledge required to better understand biopharmaceutics and to apply this knowledge in the development of drug products.

      1 [1] Levy, G. and Nelson, E. (1961). Pharmaceutical formulation and therapeutic efficacy. JAMA 177 (10): 689–691.

      2 [2] Zathurecký, L. (1977). Progress in developing a standard terminology in biopharmaceutics and pharmacokinetics. Drug. Intell. Clin. Pharm. 11 (5): 281–296.

      3 [3] Wagner, J.G. (1961). Biopharmaceutics: absorption aspects. J. Pharm. Sci. 50: 359–387.

      4 [4] Sedo, T.K. (2020). 2019 Global drug delivery & formulation report part 1 a review of 2019 product approvals. Drug Develop. Deliv. 20 (2): 18–23.

      5 [5] Amidon, G.L., Lennernäs, H., Shah, V.P., and Crison, J.R. (1995). A theoretical basis for a biopharmaceutic drug classification: the correlation of in vitro drug product dissolution and in vivo bioavailability. Pharm. Res. 12 (3): 413–420.

      6 [6] Butler, J.M. and Dressman, J.B. (2010). The developability classification system: application of biopharmaceutics concepts to formulation development. J. Pharm. Sci. 99 (12): 4940–4954.

       Hamid A. Merchant

       Department of Pharmacy, School of Applied Sciences, University of Huddersfield, Huddersfield, United Kingdom

      This chapter aims to introduce basic pharmacokinetic terminologies and principles underpinning a drug's life cycle in the body, from administration to elimination. The chapter will help readers to understand a typical pharmacokinetic profile following drug administration via absorptive versus non‐absorptive routes.

      The understanding of the critical role of absorption processes in pharmacokinetics will help in understanding how biopharmaceutics principles and strategies can modulate the pharmacokinetic profile of a drug and in turn affect the therapeutics.

      The term pharmacokinetics refers to the principles underpinning the absorption, distribution, metabolism and elimination of a drug following its administration into the body. The drug can be administered via a range of routes; many require absorption of the drug from the site of administration to get into the blood circulation, whereas drug can also be administered directly into the blood circulation (intravenously) bypassing the absorption process.

Schematic illustration of a typical life cycle of a drug in the body.

      When a drug is administered into the body, it is absorbed from the tissues where it was administered (e.g., muscles, gastrointestinal tract under the skin, etc.) to get into blood circulation. It is then distributed across the body once it is in the systemic circulation where a fraction of the drug arrives at the target sites, binds the receptors and produces a therapeutic effect. The drug is also metabolised by various tissues (mainly liver and gut) into other forms (mainly inactive) during its voyage into the body and then it is excreted out of the body, mainly via urine. The ‘pharmacokinetics’ is the study of the processes governing the ‘absorption’, ‘distribution’, ‘metabolism’ and ‘excretion’ of a drug, often referred to as ADME.

      When the drug is administered into the tissues, for example, muscles (intramuscular injection) or taken orally (tablets, capsules, etc.), it has to go through a complex absorption process before it appears in the blood. Hence, there is a significant lag time to see the therapeutic effect of the drug compared to intravenous administration. This is one reason when the intravenous route