Clearance

Abstract

This tutorial deals with basic concepts of clearance, the most important parameter in pharmacokinetics but often challenging for students in clinical pharmacology. Its relationships with dose, concentration and elimination rate are discussed using a physical model and examples of commonly used drugs, as well as its physiological aspects pertaining to the blood flow to differing organs. Finally, application of clearance to the calculation of maintenance dose rate and half-life is used to show how it is essential in pharmacotherapy and clinical pharmacology. Clinical PharmacologyWhat does pharmacology mean? Pharmacology is derived from a Greek word (pharmakon). The ancient Greeks used this word to mean a medicine, a poison or a magic spell. These 3 meanings apply today when we refer to a drug which is used for therapeutic benefit (medicine) which will always have associated adverse effects (poison) and sometimes may produce quite unexpected results (magic). The most obvious expression of magic is the placebo response.Clinical pharmacology describes the effects of drugs in humans. One way to think about the scope of clinical pharmacology is to understand the factors linking dose to effect. Drug concentration is not as easily observable as doses and effects. However, it is believed to be the key factor that explains the time course of effects after a drug dose. The science linking dose and concentration is pharmacokinetics. The two main pharmacokinetic properties of a drug are clearance (CL) and volume of distribution (V). The science linking concentration and effect is pharmacodynamics. The two main pharmacodynamic properties of a drug are the maximum effect (Emax) and the concentration producing 50% of the maximum effect (C50).The rational use of clinical pharmacology is to first decide on the desired target effect then use pharmacodynamic properties to predict the target concentration. With the target concentration it is then simple to calculate an appropriate loading dose (using V) and maintenance dose rate (using CL) to achieve and maintain the target.

Is a Lower Dose of Rivaroxaban Required for Asians? A Systematic Review of a Population Pharmacokinetics and Pharmacodynamics Analysis of Rivaroxaban

“…Detailed information on the simulated patient characteristics is provided in Table S3 . For a comparison of PK parameters, apparent clearance (CL/F) was chosen because it is the most important PK parameter for long-term pharmacotherapy and could be compared directly among studies that employed different dosing regimens [ 42 ]. As for the PD index, FXa activity was selected for comparison because it directly reflects the inhibitive effect of rivaroxaban.…”

Impact of interleukin‐6 on drug transporters and permeability in the hCMEC/D3 blood–brain barrier model

“…In the present study, digoxin was cleared by both glomerular filtration and metabolism in the liver. The extraction ratio for both organs is low [46]. According to Benet et al, changes in protein binding do not impact the unbound AUC and are not clinically relevant in this case [47].…”

An in silico investigation and introduction of some secondary metabolites of medicinal plants with antiviral activity and effective vitamins for the treatment of MPox

“…Elimination explains the rate of waste or damage (mg/h, amount per time) but clearance defines units of flow (L/h, volume per time). Therefore, the elimination of a drug than the drug concentration shows a linear function when the clearance is constant [52]. According to the description provided, although Brincidofovir is an oral drug, it is not within the approved range for blood-brain barrier (BBB) (Log BB >-1) and central nervous system permeability (Log PS>-3).…”