Fraction unbound

Cmin,ss Minimum plasma concentration at steady state fu Fraction unbound in plasma... 

Rabbit muscle homogenate binding Muscle tissue binding dominates all tissue binding and muscle binding in rabbit and human is similar Fraction unbound in muscle homogenate by dialysis [25]... 

The rate of disappearance of parent and fraction unbound can then be fed into a one-compartment PK model to produce individual or population-based estimates of the concentration at steady state (Css) that would result from a steady-state dose of 1 mg kg 1 per day of the given chemical. One can then compare the values of Css across a set of chemicals for which the exposure might be similar and make a preferential choice of the one with the lowest Css, all other factors being equal. 

Plasma protein binding fraction unbound (human) [37] 0.19 0.04... 

Recall that fu = Cu/C occurs with plasma, and also that the fraction unbound in tissues is fuT = CuT/CTW. 

Advanced treatments of pharmacokinetics introduce mathematical relationships between Vd and serum binding. Serum binding is often noted by variables such as /u (fraction unbound). Distinctions between drug that is free in the blood (/ub) and tissue (/u ) are common. 

Physiologically-Based Pharmacokinetics. Tissue-plasma partition coefficients may be calculated automatically by using only log P and fraction unbound in plasma as inputs. This module allows the user to simulate Cp vs. time profiles for drugs in discovery using only in silico or in vitro (metabolism) data inputs. 

Davis et al. (2000) discuss the problem of correcting certain pharmacokinetic values for the fraction unbound in plasma, advising caution in the approach as it may lead to spurious correlations. Values for clearance or volume of distribution of compounds have been reported in previous studies to correlate with log K. In some of these studies the correlations use values for clearance or volume of distribution that have been corrected for the fraction unbound in plasma. However, the fraction unbound in plasma is itself dependent on log K. Therefore, it is important to check that these reported correlations are genuine and not merely a reflection of the relationship between plasma protein binding and log K. ... 

The extent of protein binding in the plasma or tissues controls the volume of distribution and affects both hepatic and renal clearance. The volume of distribution (V) depends on the fraction unbound in plasma (/u), the fraction unbound in tissue (/ut), the volume of tissue (Vt), and the volume of plasma (Up) by the equation ... 

In characterising the protein binding several parameters of a drug can be experimentally determined - the unbound plasma concentration (Cu), the bound plasma concentration (cb), the fraction bound (fb), and the fraction unbound (fu). The determination can be performed at one defined concentration (e.g. 10 iM) or within a range including the pharmacological and toxicological relevant concentrations. 

Final results are given as percentile fraction unbound (fu) of percentile fraction bound (fb) for a defined concentration. 

Most pharmacokinetic theory has concentrated on explaining changes in clearance and bioavailability in terms of the parameters of intrinsic clearance, blood flow and fraction unbound [Eqs. (12) and (21)]. Yet the response of a patient to a dose or dosage regimen of a drug is dependent on the patient exposure to the drug, which is best characterized by AUC. Thus, it will be useful to consider the importance of individual parameters such as CLjnt, Q and / in terms of exposure concepts. Consider first an intravenous dose of a drug where from Eq. (7). 

Note that for oral dosing, exposure is inversely related to fraction unbound and intrinsic clearance... 

It is important to note that an increase in the /p value (fraction unbound in the plasma) caused by a displacement from drug during drug-drug interaction will cause only a transient rise in the unbound drug concentration, followed by a return to the predisplacement value when steady state has been reached.l ... 

In clinical pharmacology the fraction unbound (fa = 1 —fif) is of greater interest than the fraction bound (fi,) to plasma proteins, because it is the free drug in plasma that distributes extravascularly and interacts (activates or inhibits) with drug receptors at the site(s) of action. An increase in the fraction unbound, which may occur in certain disease states (such as hypoalbuminae-mia and uraemia) or be due to competitive displacement from albumin binding sites, can increase the intensity of the effect produced. This is of particular... 

Fraction escaping lung extraction Fraction unbound in blood Flour... 

The blood clearance can then be obtained through one of the several approaches, for example, the well-stirred model and fraction unbound (/[, obtained from plasma... 

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