Improving knowledge and safety: pharmacological principles
Sherri Ogston-Tuck in Introducing Medicines Management, 2013
Renal excretion is a complex process that involves glomerular filtration and active tubular secretion (see Figure 5.1). Within these processes drugs may have properties that allow for active secretion and reabsorption, such as the degree of alkalinity, acidity or lipid solubility. In addition, a drug’s half-life may be affected. Glomerular filtration rate (GFR) describes the flow rate of filtered fluid through the kidney and it is the measurement taken. Creatinine clearance rate, which identifies the volume of blood plasma that is cleared of creatinine per unit time, is a useful measure for approximating the GFR. The results of these tests are important in assessing the excretory function of the kidneys. For example, grading of chronic renal insufficiency and dosage of drugs that are primarily excreted via urine are based on GFR (or creatinine clearance).
Introduction
Francis L. S. Tse, James M. Jaffe in Preclinical Drug Disposition, 2017
Compounds are eliminated from the body as the unchanged molecule or as metabolite(s). As stated previously, in most excretory organs except the lungs, water soluble (polar) substances are excreted more efficiently than those that are relatively lipoidal. Although excretion can take place through numerous pathways such as the bile, feces, milk, saliva, perspiration, tears, and lungs, the most significant organ for elimination is the kidney. Renal excretion involves three processes: Passive glomerular filtrationActive tubular secretionPassive tubular reabsorption
Gastrointestinal Tract as a Major Route of Pharmaceutical Administration
Shayne C. Gad in Toxicology of the Gastrointestinal Tract, 2018
Renal clearance is the total amount of a substance excreted over a specific time period. It depends upon all sources of renal excretion. There are three processes involved in renal clearance: Tubular secretion (Suchy-Dicey et al., 2016)Glomerular filtration (Jin et al., 2008)Tubule reabsorption (Haraldsson, 2010)
Drug metabolic stability in early drug discovery to develop potential lead compounds
Published in Drug Metabolism Reviews, 2021
Siva Nageswara Rao Gajula, Nimisha Nadimpalli, Rajesh Sonti
Predicting in vivo pharmacokinetic data from the in vitro drug metabolism data is of great interest in preclinical studies. Data acquired from the in vitro metabolism helps in selecting potent leads for further development. Knowledge of drug clearance provides information about the dose required to maintain steady-state plasma concentration and drug disposition description (Chiou 1982; Bardal et al. 2011). Clearance is the volume of plasma from which the drug is removed per unit of time (Chiou 1982; Bardal et al. 2011). Plasma clearance (or total systemic clearance) can be characterized by all the metabolizing and eliminating organs involved in the drug clearance (Wilkinson and Shand 1975; Dowd 2017). These organs primarily include the liver (hepatic clearance) and kidney (renal clearance). Hepatic clearance is the liver's ability to remove the drug from the blood and is related to two variables: hepatic blood flow rate and intrinsic hepatic clearance (Wilkinson and Shand 1975). On the other hand, renal clearance is the volume of blood or plasma completely cleared off the drug by the kidneys per unit time (Tucker 1981).
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.
Pharmacotherapy options and drug development in managing periprosthetic joint infections in the elderly
Published in Expert Opinion on Pharmacotherapy, 2019
Alicia Macias-Valcayo, Bernadette G Pfang, Alvaro Auñón, Jaime Esteban
Although drugs are eliminated from the body in a number of ways, the main organ involved in excretion is the kidney. With age, overall kidney function decreases [71]. Decreased renal blood flow and glomerular filtration reduce the clearance of kidney-eliminated drugs. Reduced renal clearance of antimicrobials is directly proportional to increases in half-life. Increased half-life requires a decrease in daily doses to prevent toxicity and prolongs the time necessary to achieve steady-state serum concentrations. However, administering loading doses of vancomycin is a secure approach, which does not increase the incidence of nephrotoxicity [72]. It is important to take this into account when using antibiotics with narrow therapeutic indices (the ratio of effective to toxic serum concentrations) that require serum concentration monitoring [73], and in some cases, drug dosing must be based on renal function [74].
Related Knowledge Centers
- Excretion
- Hemodialysis
- Nephron
- Peritubular Capillaries
- Physiology
- Pharmacokinetics
- Pharmacology
- Blood Plasma
- Glomerular Filtration Rate
- Kidney