Clint equation

Equation (1) was derived assuming no protein binding, whereas, in fact, CLint should be defined in terms of the maximum ability of the organ to remove unbound drug because only unbound drug can bind to enzymes and excretory molecules. By including the unbound fraction of drug in Eq. (4) one obtains... 

Measurements of the rate of deposition of particles, suspended in a moving phase, onto a surface also change dramatically with ionic strength (Marshall and Kitchener, 1966 Hull and Kitchener, 1969 Fitzpatrick and Spiel-man, 1973 Clint et al., 1973). This indicates that repulsive double-layer forces are also of importance to the transport rates of particulate solutes. When the interactions act over distances that are small compared to the diffusion boundary-layer thickness, the rate of transport can be computed (Ruckenstein and Prieve, 1973 Spiel-man and Friedlander, 1974) by lumping the interactions into a boundary condition on the usual convective-diffusion equation. This takes die form of an irreversible, first-order reaction on tlie surface. A similar analysis has also been performed for the case of unsteady deposition from stagnant suspensions (Ruckenstein and Prieve, 1975). 

Clint el al. (4) measured the rate of deposition of 0.43-gm-diameter polystyrene latex particles onto a rotating disk coated with a polystyrene film in Ba(N03)s solutions of three different ionic strengths. Results are reported ia Table II. Also reported in this table are the surface potentials of the disk which are needed to force agreement between predicted and observed rates. Speculations 1 and 2 again refer to approach at constant surface potential or charge, respectively, when the potential is small enough to linearize the Poisson-Boltzmann equation. However, when the... 

The principle for the bioavailability estimate is as follows [84], Hepatic intrinsic clearance (CLint) is measured in hepatocytes by measuring the half-life (t1/2) in the following equation ... 

Compared to gut first pass, liver first pass is easier to estimate using CLmt measured in vitro, due to the homogenous physiology of the liver. Fh can be estimated with CLint obtained by in vitro system with this equation ... 

This means that overall exposure to unbound drug can t be affected by plasma binding or plasma protein binding displacement interactions. Furthermore, if the drug is a high hepatic extraction-ratio drug, such that CLint >Qj then Q hepatic blood flow rate, becomes limiting, and Equation (12.31) becomes ... 

When /u-Clint is very small in comparison to hepatic blood flow C/u-Clint < Q), the equation reduces to ... 

If CLint is determined in vitro and if / is known, the important PK parameters (CLh, F, and h) ean be directly estimated using Eq. 13.14-13.16, assuming that Qh is constant, that is, 1.5 L/min, or approximately 21 mL/min/ kg for humans (Davies and Morris, 1993). Moreover, if nonspecific protein binding in the in vitro assay systems is factored into the equations, / should be replaced by //u, where/ is the unbound fraction in the in vitro metabolic systems, whieh can be determined using equilibrium dialysis (Soars et al., 2002). Therefore, Eq. 13.14 can be expressed as... 

Equation (6.16) demonstrates that AUCoral is independent of Qi, and inversely proportional to CLint, h- This relationship is quite important in the screening of new drug candidates. However, it must be kept in mind that Eqs. (6.15) and (6.16) are derived using the well-stirred model. Thus, the prediction error may be significant for high-clearance drugs. 

It is well known that the air/solution interface of an amphiphile solution is well populated (Clint, 1992) by the adsorbed molecules. Accordingly, it has been shown that the concentration of the surfactant is always greater at the surface due to adsorption over and above the concentration of surfactant in the bulk. For calculation of Gibbs free energy changes, required different surface properties (e.g., the surface excess concentration, Tmax, minimum area per surfactant molecule at the air/water interface, Amin etc.). The surface excess concentration is an effective measure of the Gibbs adsorption at liquid/air interface, which was calculated by applying equation (Chattoraj Birdi, 1984)... 

Aveyard and Clint [85] have analyzed the consequences of the presence of a significant line tension on the behavior of lenses for the role of liquid drops in the rupture of thin liquid films and hence in foam breaking. They note, for example, that Equation 4.35 indicates that a sufficiently high positive value for x could mean that the equilibrium entry coefficient becomes negative for small drops in the case... 

The same technique was used by Clint et al. [108] for the determination of the surface of carbon black by the adsorption of n-alkanes. Equation (5.21) was used with the following correction for small particles where the thickness of the adsorbed layer t was not negligible in comparison with the particle radius r ... 

---