The basics of clinical pharmacology
Conrad Harris, Jane Richards in Prescribing in General Practice, 2018
Most drugs are absorbed by passive diffusion, in that they pass through the lipid membrane of the mucosal cell walls passively. A small number use existing active absorption mechanisms, e.g. L-dopa. Most drugs are not completely absorbed – some are lost in the large bowel where they may have side effects, e.g. ampicillin causing diarrhoea. Once absorbed, the drug enters the portal venous system which carries it to the liver and then to the systemic circulation. Many drugs undergo some metabolism before entering the systemic circulation, either in the wall of the bowel or the liver. This is called first-pass metabolism, and its extent may vary from person to person. The term bioavailability describes the amount of the drug administered that reaches the systemic circulation (after absorption and first-pass metabolism) and is usually expressed as a percentage.
Drug Absorption and Bioavailability
Kate McCombe, Lara Wijayasiri, Paul Hatton, David Bogod in The Primary FRCA Structured Oral Examination Study Guide 2, 2017
Define bioavailability. Bioavailability describes the fraction of the drug administered that reaches the bloodstream.If a drug is given intravenously it is introduced straight into the bloodstream and is said to have a bioavailability of 1 or 100%.For drugs given orally, the bioavailability is calculated by comparing the plasma concentration of the drug when administered orally to the plasma concentration when it is administered intravenously. This is achieved by comparing the area under the curve (AUC) of the two conditions:
Bioavailability and Granule Properties
Dilip M. Parikh in Handbook of Pharmaceutical Granulation Technology, 2021
The subject of bioavailability began to receive growing attention as studies showed that the therapeutic effectiveness of a drug from the dosage form depends, to a large extent, on the physiological availability of their active ingredient(s) and is a function of the drug concentration in the patient's blood or plasma. The importance of bioavailability in drug therapy, therefore, stems from the fact that the rate and extent of absorption of a drug from a dosage form can affect the patient's response to a drug. In light of these facts, the determination of bioavailability has become one of the ways to assess the in vivo performance of a dosage form following its formulation development. It must, however, be remembered that bioavailability studies, very often, are conducted in normal, fasted, and a small number of subjects, and therefore, the results of these studies may not always reflect the true efficacy relationship in patients under treatment conditions. For many years, it was assumed that if a dosage form contained the labeled amount of a drug, its performance could be taken for granted. However, it is now evident for some time that many factors acting individually or in concert may produce therapeutic failure.
Buprenorphine implants: a model for expedited development and approval of new drugs
Published in Current Medical Research and Opinion, 2021
Michael Guarnieri, Jayanidhi Kedda, Betty Tyler
Generic drugs are defined as chemical products having the same molecular formula with similar manufacturing processes and inactive ingredients as the original product. These drugs have an expedited regulatory approval pathway1. Sponsors of the new product must demonstrate that the applicant drug has the same safety profile and affords the same bioavailability, that is, blood concentrations equivalent to the therapeutic concentrations of the referenced drug. Bioavailability thus refers to the extent and rate at which the drug enters systemic circulation, thereby accessing the site of action. Complex efficacy tests are not required for approval. Rather, efficacy can be inferred by demonstrating comparable bioavailability between the new and referenced product. This pathway allows medicines to reach the patient without going through time consuming clinical trials for effectiveness if the new product demonstrates safety and functional equivalence to the drug that already has been through these tests.
Preparation, characterization, and pharmacokinetics study of a novel genistein-loaded mixed micelles system
Published in Drug Development and Industrial Pharmacy, 2018
Hongxue Shen, Dandan He, Shuxia Wang, Pinggang Ding, Jianan Wang, Jianming Ju
Bioavailability is an important indicator used to evaluate the effectiveness of drugs. A low bioavailability indicates that the drug cannot be absorbed into the blood, resulting in poor curative effect. As described in Biopharmaceutical Classification System (BCS), the two key parameters that govern the overall process of oral drug absorption are drug solubility in the aqueous gastrointestinal tract (GIT) and drug permeability through the intestinal membrane [42,43]. GEN has a low solubility in both water and gastrointestinal pH (only about 10 µg/mL); therefore, it must be solubilized during oral administration to ensure that the dissolution of GEN does not constitute a rate-limiting factor for absorption. GEN has high membrane permeability, but efflux phenomenon is one of the reasons influencing its absorption in the GIT. In vivo bioavailability testing further confirmed that GEN-M increased the plasma concentration of GEN and improved its bioavailability, possibly because of the following reasons: GEN-M increased the solubility of GEN and surfactants increased the intestinal epithelial permeability by disturbing the cell membrane and inhibiting the efflux phenomenon.
Mathematical modelling of drug-diffusion from multi-layered capsules/tablets and other drug delivery devices
Published in Computer Methods in Biomechanics and Biomedical Engineering, 2022
Drugs are chemical or biological compounds that affect the human body and its functioning. The drug delivery to the biological tissues through diffusion and absorption occurs when it enters the circulatory system. The level of absorption can affect the speed and amount of the drug and its side of action. This is called bioavailability. If a tablet/capsule or some other drug delivery device (DDD) releases the drug quickly, blood levels may become too high whereas slow release may result in low levels of absorption. Addition of factors affecting bioavailability and absorption of the drugs, include properties of the drug and the physiology of the person, such as pH levels in the stomach and its speed of emptying. Therefore, specific formulations are used to release the drug at a desired speed. Common formulations include capsules, tablets, transdermal patches, solutions and other DDDs (Borchardt et al. 1996). To this end, mathematical modeling of diffusional and release processes provides detailed insights to simulate the biological systems and biomedical phenomena with the aid of computational power (Sidig 2015). To depict the desired release of the drug (from a capsule/tablet or other DDDs), to the targeted biological tissue, mathematical models in drug delivery have played a vital role to design and shape the drug delivery systems (Peppas and Narasimhan 2014).
Related Knowledge Centers
- Absorption
- First Pass Effect
- Circulatory System
- Pharmacology
- Medication
- Intravenous Therapy
- Route of Administration
- Area Under The Curve
- Standard Deviation
- Therapeutic Index