Drug transport experimental rate constants

Figure 3 Experimental rate constants of drug transport of 30 sulfonamides and 15 standard compounds, including several drugs. (From Refs. 56 and 57.) The rate constants k (from the aqueous phase into the organic phase) and k2 (the reverse rate constant) are fitted by Eqs. (28) and (29).

The bilinear model is confirmed by simulations, using experimental rate constants of drug transport, which were determined from the time dependence of substance concentrations in the different phases of a three-compartment system water/n-octanol/water (Figure 15) [443]. 

An alternative to the parabolic model is the bilinear model (equation 6) which was derived from computer simulations, using experimental rate constants of drug transport in simple in vitro systems. " In most cases it describes nonlinear lipophilicity-activity relationships more accurately than the parabolic model. 

Uptake of the amides into L1210 cells, was considerably slower than that of the parent acid, as indicated by values for unidirectional influx (measured by titration of drug in cell lysates with DHFR) or X values for competitive inhibition of [ H]MTX transport [240]. The values of the amides ranged from 3.3 rM for (VIII.188) to 48 rM for (VIII.194), while the for MTX uptake by these cells was 3.3 /rM. First-order rate constants for efflux, on the other hand, were hardly affected by y-substitution. Transport into the cells was therefore predicted to be the limiting event for cell growth inhibition, and this was experimentally borne out by growth inhibition assays with... 

Because the amounts and density of these transporters vary along the gastrointestinal tract, it is necessary to introduce a correction factor for the varying transport rates in the different luminal and enterocyte compartments. Due to the lack of experimental data for the regional distribution, and Michaelis-Menten constants for each drug in Table 18.2, we fitted an intrinsic (concentration-independent) transport rate for each drug to closely approximate the experimental %HIA. This... 

The last equation reveals that estimates for P can be obtained in an experimental setup if the permeation rate q (/,) and the total membrane area A available for transport are measured and the drug concentration c (t) in the donor compartment remains practically constant. What is implicit from all the above is... 

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