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Pharmacokinetic-Pharmacodynamic Correlations of Anesthetic Agents
Published in Hartmut Derendorf, Günther Hochhaus, Handbook of Pharmacokinetic/Pharmacodynamic Correlation, 2019
Virginia D. Schmith, Keith T. Muir
Classical and population PK/PD modeling approaches have been utilized to define the effect of age on the dosing requirements of thiopental.22,89 Originally, Homer and Stanski23 reported a smaller initial volume of distribution in elderly patients than in young patients, with no differences in the arterial plasma thiopental concentration-spectral edge relationship. Thus, these authors concluded that the dose required to produce induction of anesthesia should be reduced in elderly patients. Subsequently, Stanski and Maitre89 re-examined the effect of age on thiopental pharmacokinetics and pharmacodynamics. These investigators reported that intravenous (IV) bolus administration of thiopental did not allow accurate characterization of the distribution of the drug. Rapid IV infusions permitted a more accurate determination of the initial distribution characteristics of thiopental. In this study, initial volume of distribution was not related to age as previously reported. Instead, the intercompartmental clearance of thiopental was lower in elderly patients than in young adult patients. As reported earlier, there were no differences in IC50, Eo, Emax, or s between elderly patients and young adult patients.89 Therefore, thiopental pharmacokinetics are altered in elderly patients but brain sensitivity remains unchanged.
The Role of Kinetic Analysis and Mathematical Modeling in the Study of Bilirubin Metabolism in Vivo
Published in Karel P. M. Heirwegh, Stanley B. Brown, Bilirubin, 1982
E. Anthony Jones, Ewart R. Carson, Paul D. Berk
Clinically useful and physiologically meaningful results can be obtained from analyses of radioactivity-time curves which are independent of any specific compartmental model of the system being investigated. Two important model independent parameters are the initial volume of distribution or initial mixing compartment of an injected labeled substance and the fractional turnover rate of the unlabeled endogenous substance in that compartment. The initial volume of distribution (V) is given by the following equation:
Disposition of oral delta-9 tetrahydrocannabinol (THC) in children receiving cannabis extracts for epilepsy
Published in Clinical Toxicology, 2020
George Sam Wang, David W A Bourne, Jost Klawitter, Cristina Sempio, Kevin Chapman, Kelly Knupp, Michael F. Wempe, Laura Borgelt, Uwe Christians, Kennon Heard, Lalit Bajaj
There are various products derived from Delta-9 Tetrahydrocannabinol (THC) available in pediatrics for chemotherapy-induced nausea and vomiting, including dronabinol and nabilone [1]. These products have been given Schedule III and II classifications by the Drug Enforcement Administration. Despite plant-derived marijuana products and extracts being given a Schedule I designation, there is wide use of these products for several medical indications, including pain, muscle spasm, nausea, and cachexia. More than half of US states have legalized marijuana for medical indications, which includes use in the pediatric population (http://www.ncsl.org/research/health/state-medical-marijuana-laws.aspx). In July 2018, there were 312 patients less than 18 years of age listed in the Colorado Medical Marijuana Registry, almost half (142, 46%) using marijuana for severe pain (https://www.colorado.gov/pacific/sites/default/files/CHED_MMR_Monthly_Report-July-2018.pdf). The dose taken by children varies, and known THC pharmacokinetic data is based on adult research. In adults, oral bioavailability is estimated to range from 4–12%, with peak concentrations mostly within 1–2 hours, but as late as 4–6 hours. Most (90%) of THC is distributed in the plasma, 10% in red blood cells, with an initial volume of distribution (Vd) of 2.5–3 L. Metabolism mainly occurs by liver hydroxylation and oxidation by cytochrome p450 enzymes, main metabolites are THC-COOH and THC-COOH glucuronide (Figure 1). Terminal half-life of elimination for THC ranges from 25 to 36 hours and is longer for metabolites [2–4].