China
Africa
Explore chapters and articles related to this topic
Influence of medication on typical exercise response
Published in R. C. Richard Davison, Paul M. Smith, James Hopker, Michael J. Price, Florentina Hettinga, Garry Tew, Lindsay Bottoms, Sport and Exercise Physiology Testing Guidelines: Volume II – Exercise and Clinical Testing, 2022
The rate at which a drug is metabolised and excreted from the body is termed its half-life. The half-life of a drug is the time taken for the plasma concentration of a drug to reduce to half its original value. Conventionally, in pharmacology, half-lives follow the principle of first-order kinetics in which the rate of elimination is constant, irrespective of the concentration of the substance (Ritter et al., 2019), as illustrated in Figure 1.5.1. Following a lapse of time equivalent to five half-lives, less than 97% of the starting concentration remains: at this time, in biological terms, we deem a substance to be eliminated. For example, if a medication has a half-life of 5 hours, one would consider someone drug-free after a 25-hour washout period.
Therapeutic Potential of Anthocyanin Against Diabetes
Published in Hafiz Ansar Rasul Suleria, Megh R. Goyal, Health Benefits of Secondary Phytocompounds from Plant and Marine Sources, 2021
Tawheed Amin, H. R. Naik, Bazila Naseer, Syed Zameer Hussain
Bioavailability defines the kinetics and the degree to which a bioactive agent is assimilated from any ingested food and its availability at the target site-of-action [35]. The therapeutic effects of the natural colorant (anthocyanin) are dependent on sufficient bioavailability possibly due to their complex biochemistry [82].
High-Performance Liquid Chromatography
Published in Adorjan Aszalos, Modern Analysis of Antibiotics, 2020
Joel J. Kirschbaum, Adorjan Aszalos
Cephaloglycin and its metabolite desacetylcephaloglycin were determined in urine using an octadecylsilane analytical column and guard column with a mobile phase of water-methanol (4:1) containing 0.01 M aqueous ammonium dihydrogen phosphate and 0.004 M sodium n-heptylsulfonate. The flow rate was 1 ml/min into a 254 nm detector [203]. Kinetics and pharmacology were discussed.
Non-human primates in the PKPD evaluation of biologics: Needs and options to reduce, refine, and replace. A BioSafe White Paper
Published in mAbs, 2022
Karelle Ménochet, Hongbin Yu, Bonnie Wang, Jay Tibbitts, Cheng-Pang Hsu, Amrita V. Kamath, Wolfgang F. Richter, Andreas Baumann
Lenercept is an Fc-fusion protein consisting of the extracellular domain of two human p55 tumor necrosis factor receptors fused to the Fc portion of human IgG1.75 The PK of lenercept was characterized in several animal species, including cynomolgus monkeys, to support planning of toxicity and pharmacology studies, as well as for predicting the PK in humans by allometric scaling. Lenercept was found to be immunogenic in all animal species tested. In monkeys, the immune response was evident from an accelerated clearance of lenercept starting at 10 days post-dose in all four animals tested and was confirmed by appearance of ADA in plasma samples collected 19 days after dosing. In the PK non-compartmental analysis (NCA), the period of accelerated clearance was disregarded, as the ADA-mediated accelerated clearance does not reflect the disposition kinetics of the drug itself. This meant that the PK could be followed only over 10 days, which results in an uncertainty in the PK parameters assessed by NCA. This uncertainty is considered acceptable, as the PK could be characterized over about two half-lives. Despite these shortcomings, the obtained PK parameters in cynomolgus monkey are predictive for humans. Using state-of-the-art scaling procedures from monkeys to humans with an allometric exponent of 0.85 for clearance, the lenercept clearance of 12 mL/day/kg in monkey results in a projected human clearance of 7.6 mL/day/kg, calculated for a 70 kg subject.29 This value is in excellent agreement with the observed value of 6.8 mL/day/kg.76
Evolution of the drug-target residence time model
Published in Expert Opinion on Drug Discovery, 2021
If we now consider the fate of an enterally administered drug, we come to realize that a number of macroscopic processes (e.g. gastrointestinal absorption and tissue distribution from systemic circulation, both of which occur at much slower rates than that of typical bimolecular association) impede the rate at which a drug molecule reaches its intended, tissue-localized target. Additionally, drug metabolism and elimination processes continuously diminish the concentration of total drug within the body over time. Hence, in vivo, equilibrium conditions do not apply to drug-target interactions; instead, the concentration of drug impinging on its target is in constant flux. Under these conditions, it is the kinetic rates of binding and dissociation, rather than the equilibrium constant, that determine the duration of target occupancy in the tissue – i.e. the duration of drug residence on its target.
Metallic nanoparticles as drug delivery system for the treatment of cancer
Published in Expert Opinion on Drug Delivery, 2021
Munira Momin, Tabassum Khan, Sankalp Gharat, Raghumani Singh Ningthoujam, Abdelwahab Omri
The pharmacokinetics and toxicity profile is considered to be a crucial point during the design, synthesis and development of metallic NPs [20]. It is important to study pharmacokinetic parameters, viz. maximum concentration (Cmax), time to attain maximum concentration (Tmax), the volume of distribution (Vd), clearance (Cl), half-life (T1/2), an area under the curve (AUC), and bioavailability (F) for determining the rate of absorption, distribution, metabolism, and excretion profile of the metallic NPs [32,196]. The pharmacokinetic variables can be determined by various kinetic and mathematical models [32]. If higher circulation time of NP is the objective, then increased AUC, T1/2, and reduced Cl rate is desired [197]. On the contrary, if low circulation time of a drug or NP is the aim, then lower AUC, T1/2 and higher Cl rate are desired [198–200]. Therefore, pharmacokinetic data impart perception into calculating the dose regime in order to maintain a suitable plasma concentration for optimistic therapeutic effect [20,197,201]. Additionally, the retention of the drug or the metallic NP at the tumor cell is highly preferable for prolonged and optimal therapeutic effect and contrarily the higher distribution of the drug or a metallic NP to the non-target organs may cause severe toxicity or unwanted side effects. Hence, pharmacokinetics and biodistribution studies are pivotal for efficacious and safe drug delivery at the target site [202,203].