China
Africa
Explore chapters and articles related to this topic
Tubular Function
Published in Peter Kam, Ian Power, Michael J. Cousins, Philip J. Siddal, Principles of Physiology for the Anaesthetist, 2020
Peter Kam, Ian Power, Michael J. Cousins, Philip J. Siddal
Inulin is freely filtered by the glomerulus and is not reabsorbed, secreted, metabolized or synthesized by the renal tubules. The amount of inulin filtered at the glomerulus is the same as the amount that appears in the urine. The renal clearance of inulin is therefore equal to the volume of fluid filtered from the glomerular capillaries into Bowman's capsule per unit time. Inulin clearance is used as a reliable estimation of GFR, which is 125 mL/min or 180 L/day (accurate measurement of the GFR requires the use of a continuous infusion technique to establish a constant plasma inulin concentration and a steady renal excretion rate).
Antiviral therapeutics for viral infections of the central nervous system
Published in Avindra Nath, Joseph R. Berger, Clinical Neurovirology, 2020
Renal excretion is the major route of elimination. After oral administration of famciclovir, penciclovir accounts for 82% of urinary drug-related material. The remainder includes metabolites, of which the largest is the 6-deoxy precursor of penciclovir. Renal clearance exceeds glomerular filtration, indicating renal tubular secretion [25].
Overview of the Biotransformation of Antiepileptic Drugs
Published in Carl L. Faingold, Gerhard H. Fromm, Drugs for Control of Epilepsy:, 2019
In the liver biotransformations are catalyzed by enzymes located primarily in the smooth endoplasmic reticulum (microsomes), although several important enzymes are found in liver cell cytosol and in mitochondria. The most important and most studied of the drug-metabolizing enzymes is cytochrome P-450. Cytochrome P-450 is a heme-containing enzyme that catalyzes many drug oxidations (see below). Cytochrome P-450 is the terminal oxidase of an electron transfer system that ultimately ends up with oxygen being added to the drug molecule. Some of the more important consequences of this addition of oxygen are drug hydroxylations, epoxidation and N-, O-, or S-dealkylations. The liver enzyme biotransformations are conveniently classified as phase I and phase II reactions. Phase I reactions usually involve the addition or uncovering of active sites on the drug molecule; phase II reactions conjugate the drug molecule with endogenous body constituents, such as glucuronic acid. Both phase I and phase II reactions produce drug molecules that are more water soluble than are the parent drugs. Thus, renal excretion is increased and the sojourn of the drug in the body is decreased. Some details of phase I and phase II drug modifications are summarized in Sections B and C below.
Machine learning models using non-linear techniques improve the prediction of resting energy expenditure in individuals receiving hemodialysis
Published in Annals of Medicine, 2023
Alainn Bailey, Mohamed Eltawil, Suril Gohel, Laura Byham-Gray
The original studies in the RNKD were convenience-sampled in the Northeast and Midwest regions of the USA and hence the population was not as diverse as the national average. Additionally, those studies imposed strict medical criteria which resulted in the omission of sicker individuals. Many key variables (anthropomorphic and IC) were gathered on a non-dialysis day. This could affect a post-dialysis weight and BMI, dependent on an individual’s fluid intake and residual renal excretion. Only conventional hemodialysis was undertaken in the original studies. This gives limited insight into the clinical feature differences that may be attributable to peritoneal dialysis or more advanced techniques (such as hemodiafiltration or expanded hemodialysis). Future research should undertake a more comprehensive review of dialysis procedures. For the purpose of this study, certain variables were omitted from the ML dataset to preserve the number of subjects available for training and validation. This includes key clinical markers such as CRP, hemoglobin A1c and serum creatinine which have been previously shown to correlate with mREE. Notwithstanding the omissions of variables, the validation set only comprised of 34 individuals, which represents a small sample size. Finally, the best model (SVR) gave substantially improved precision and a glimpse into the features that may contribute. However, the model does not generate an equation and is, therefore, less interpretable as to the direction of effect.
Lasmiditan: an additional therapeutic option for the acute treatment of migraine
Published in Expert Review of Neurotherapeutics, 2021
Daniele Martinelli, Vito Bitetto, Cristina Tassorelli
Lasmiditan is rapidly absorbed after oral administration [38,39] (average Tmax = 1.8 hours) also during the migraine attacks. Even though high-fat meals can modify some parameters (increase in Cmax and AUC by 22% and 19%, respectively), RCTs showed that the efficacy of the drug is not affected by food intake. At therapeutic concentrations, the drug is quite strongly bound by plasma proteins (55–60%) and is then eliminated with a geometric mean t½ value of approximately 5.7 hours; no accumulation was observed with daily dosing [39,40]. The primary elimination is through metabolism, mainly with ketone reduction, while renal excretion is a minor route of clearance. Lasmiditan undergoes hepatic and extrahepatic metabolism primarily by non-CYP enzymes. Significantly, many important enzymes are not involved in its metabolism: MAO-A, MAO-B, flavin monooxygenase 3, CYP450 reductase, xanthine oxidase, alcohol dehydrogenase, aldehyde dehydrogenase, aldo-keto reductases. On the other hand, lasmiditan inhibits P-glycoprotein (P-gp) and BCRP in vitro, therefore the concomitant use of lasmiditan and drugs that are substrates of P-gp or breast cancer resistance protein (BCRP) should be avoided.
Development, validation and application of physiologically based biopharmaceutics model to justify the change in dissolution specifications for DRL ABC extended release tablets
Published in Drug Development and Industrial Pharmacy, 2021
Swati Jaiswal, Tausif Ahmed, Sivacharan Kollipara, Mohit Bhargava, Siddharth Chachad
Clearance of API included contributions from both intestine and liver estimated by Michaelis-Menten kinetics for UGT1A4 (in vitro kinetic parameters, Km (550 µM) and Vmax (153 pmol/min/mg protein) obtained in human liver microsomes were converted to in vivo clearance using the Metabolism and Transporter Units Converter in Gastroplus [12]. Austin method was used for calculating in vitro fraction unbound. Additionally, clearance from renal excretion was fixed at 0.2 L/h based on the literature value [13]. The theoretical method for estimating passive renal filtration [Fup*GFR] was over predicting the renal excretion. The resulting CL was lower than the observed in vivo human CL, thus UGT1A4 Vmax was increased to 475 pmol/min/mg protein to match the i.v. human CL obtained using non-compartmental analysis.