A pharmacokinetic model, with Michaelis-Menten elimination, has been developed for drugs and propranolol in particular. The theory is given and the relationship between the area under the theoretical plasma level curve and the absorption rate constant is discussed. This approach allows for an explanation of many of the observed pharmacokinetics of 'Inderal' and particularly 'Inderal' LA; a sustained release preparation of propranolol. In particular, the bioavailability, as measured by area under the curve, is found to be strongly dependent on the absorption half-life in agreement with experimentally observed data.
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http://dx.doi.org/10.1007/BF03189748 | DOI Listing |
Arch Toxicol
February 2025
Oregon State University, Corvallis, OR, USA.
The kinetically-derived maximal dose (KMD) is defined as the maximum external dose at which kinetics are unchanged relative to lower doses, e.g., doses at which kinetic processes are not saturated.
View Article and Find Full Text PDFBiochem Biophys Res Commun
December 2024
Department of Natural Science, Federal University of São João del-Rei, São João del-Rei, MG, 36301-160, Brazil. Electronic address:
Cancer Sci
December 2024
Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Republic of Korea.
ABL001/CTX-009 is a bispecific antibody targeting delta-like ligand-4 and vascular endothelial growth factor A. In this study, we developed a population pharmacokinetic (PK) model of ABL001/CTX-009 in patients with solid tumors. A total of 712 plasma concentrations from 30 patients with relapsed or refractory solid tumors were collected from a phase 1 study (NCT03292783).
View Article and Find Full Text PDFBiochemistry
October 2024
Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States.
As a traceless, bioreversible modification, the esterification of carboxyl groups in peptides and proteins has the potential to increase their clinical utility. An impediment is the lack of strategies to quantify esterase-catalyzed hydrolysis rates for esters in esterified biologics. We have developed a continuous Förster resonance energy transfer (FRET) assay for esterase activity based on a peptidic substrate and a protease, Glu-C, that cleaves a glutamyl peptide bond only if the glutamyl side chain is a free acid.
View Article and Find Full Text PDFChembiochem
November 2024
State Key Laboratory of Biobased Material and Green Papermaking (LBMP), Qilu University of Technology, Jinan, Shandong, China.
Cytochrome P450 (CYP450) enzymes, which are widely distributed and pivotal in various biochemical reactions, catalyze diverse processes such as hydroxylation, epoxidation, dehydrogenation, dealkylation, nitrification, and bond formation. These enzymes have been applied in drug metabolism, antibiotic production, bioremediation, and fine chemical synthesis. Recent research revealed that CYP450 catalytic kinetics deviated from the classic Michaelis-Menten model.
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