Drugs calculating value

Many excellent computer programs are available for predicting log P a from two-dimensional structures. The quality of predictions has risen over the years to the point that rouhne log P a measurements are not regularly done at some pharmaceutical companies, but rather, calculated values are used. It is worth noting that log Port values of newly synthesized classes of drug-like compounds sometimes are still poorly predicted and probably there will be the need for judicious log Port measurements for years to come. 

Moriguchi, I., Hirono, S., Nakagome, 1., Hirano, H. Comparison of reliability of log P values for drugs calculated by several methods. Chem. Pharm. Bull. 1994, 42, 976-978. 

Aleksic et al. [47] estimated the hydrophobicity of miconazole and other antimycotic drugs by a planar chromatographic method. The retention behavior of the drugs have been determined by TLC by using the binary mobile phases acetone-n-hexane, methanol toluene, and methyl ethyl ketone toluene containing different amounts of organic modifier. Hydrophobicity was established from the linear relationships between the solute RM values and the concentration of organic modifier. Calculated values of RMO and CO were considered for application in quantitative structure activity relationship studies of the antimycotics. 

Polyacrylic nanoparticles have been prepared to investigate their use as colloidal drug carriers, and surface area measurements were used for characterization [14], When the experimental surface area values were compared with calculated values, it was found that the measured surface area value was 10 times smaller than the calculated value. The discrepancy was explained by the surfactant used in the nanoparticle preparation. The surfactant appears to coat the particles when it is not completely removed, resulting in the low surface areas observed for the particles. Particles prepared without surfactant showed good agreement with the calculated values. 

Another term which is important in pharmacokinetics is the half-life (fi/2) of a drug. This value is related to the Vd and the total clearance. If it is assumed that the body is a single compartment in which the size of the compartment equals the Vd, the fi/2 may be calculated from the equation ... 

What requirements must parameters fulfil in order to be suitable in the search for new drugs The type of parameter which is principally suitable depends on the respective problem, i.e. whether we are concerned with series design or with derivation of structure-activity-relationships. In the former case only parameters which can be calculated directly from the chemical structure can be used whereas in the latter case one can also (and preferably) apply measured parameters. Thus, measured log P values as well as calculated ones ( ) are suitable in structure-activity-analysis, whereas for series design lipophilicity can only be represented by the calculated values. 

Table II shows renal excretion data. Calculated values were obtained from Equations 38, 44, 47, and 52. Here, the rate constants of acetosulfamine and sulfadimethoxine are as well correlated as those of the other compounds for rats and rabbits. This could be expected since the kEx value is directly determined by the proportion of the integrated amount of non-metabolized drug in the total urinary excreted materials whereas the kAc value is derived by assuming that metabolites, other than N-4-acetyl derivatives, are negligible in the urine. For humans, the rate constant of sulfadimethoxine is well correlated while that of acetosulfamine is not. The latter may be excreted by a different mechanism as mentioned.

Hence we can make more sense of this calculated value by taking its inverse as 1/0.27 = 3.75. This expression is more appealing and an accurate interpretation in that patients treated with the test drug are 3.75 times more likely to attain the SBP goal than those treated with placebo. One can also obtain this result by switching the order of the columns in Table 10.3 and performing the calculation as ... 

Despite all their limitations, such predictions of skin permeability may be valuable and have several important potential uses. Ranking of drugs in order of potential dermal penetration is probably the most valuable use in the pharmaceutical field. For example, in situations where it is necessary to predict the dermal penetration potential for a series of homologous or closely related drugs, it is possible to rank the compounds using theoretical calculations. However, in order to validate the calculated values, it is essential to experimentally determine the skin permeation properties of several representative compounds of the group in a relevant vehicle. 

The term "clearance" refers to the volume of fluid that would be completely cleared of drug (per unit time) if aU the drug being excreted/metabolized were removed from that volume (and the remaining fluid in the body retained the original concentration of drug). "Qearance" is a calculated value that cannot be directly measured in the body. It is measured in liters per hour, but is often mistaken for "rate of elimination" which is eported as mg/hr. Clearance values can be calculated for specific systems. For example, total clearance =... 

Since the calculated value of MRT is the average time a typical drug molecule is present in the body, from the time it is administered up to the time it is eliminated, MRT will have a different physical significance depending on how the drug was administered and whether or not there is an absorption step. 

Comparison of Reliability of LogP Values for Drugs Calculated by Several Methods. 

Recall trom basic mermodyiiainics that a j,ocess with a negative AG is spontaneous and the product—here, the solvated state—is favored relative to the unsolvated state. The authors of ffie study proposing this alternative approach derived a relationship that exhibited a reasonable correlation with measured values of LogBB. Some values obtained for AG°vv were —5.00 for ethanol (freely water soluble) and 2.08 for hexane for AG°hu the values were —0.16 and —3.45, respectively, for the same compoimds. Caffeine, a water-soluble basic drug, had calculated values of —15.27 and —9.31, respectively. The difference in the AG° values suggests that caffeine is more stable when it is solubilized in water than in a lipophilic medium. In the case of caffeine, the calculated LogBB veilue of 493 compared reasonably well with an experimental value of 40.3. 

Figure 16 Comparison of measured log P values for 22 drugs and calculated values. (Ref. 193.)...

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