Rowland fractionation method

The nitrogen content of milk is distributed among caseins (76%), whey proteins (18%), and NPN (6%). This does not include the minor proteins and glycoproteins that are associated with the fat globule membranes (FGM). This nitrogen distribution can be determined by the Rowland fractionation [85] method given in Table 3.12. 

Various procedures are used to separate milk proteins into fractions or individual components that can quantitated separately. A classic method of fractionation is by precipitation at pH 4.6, which separates the proteins into two groups—caseins in the precipitate and whey proteins in the supernatant. All proteins are precipitated from a second aliquot with trichloroacetic acid at 12% (w/v) concentration (Rowland 1938), and concentrations of casein and whey proteins are calculated as follows ... 

To address the inaccuracy of estimates for volume at steady state (Vss) for strongly basic drug molecules, Rodgers and Rowland have proposed an extension to the tissue composition method that takes into account the volume fraction of acidic phospholipids. Presumably, the higher values of Vss observed for these basic molecules is due to the interaction of the cationic state (at physiological pH) of the base with the anionic state of the acidic phospholipids [82-85], Several commercial software programs are now extensively used in the pharmaceutical industry for PBPK modeling [86, 41, 87, 11]. 

If specific literature recommendations and/or the relationship of kinetic parameters to CLcr are not available, then one can estimate the kinetic parameters of the patient with the method of Rowland and Tozer, provided you know the fraction of the drug that is eliminated renaUy unchanged (f ) in subjects with normal renal function. This approach assumes that the change in CL and k are proportional to CLcr, that renal disease does not alter the drug s metabolism, that the metabolites if formed are inactive and nontoxic, that the drug obeys first-order (linear) kinetic principles, and that it is adequately described by a one-compartment model. If these assumptions are true, then the kinetic parameter/dosage adjustment factor (Q) can be calculated as ... 

The Poulin and Theil (homogeneous and extracellular), Berezhkovskly and Rodgers, Leahy, and Rowland methods for calculating partition coefficients are among those available in the program. The Poulin and Theil and Berezhkovskly models take into consideration the volume fractions of water, phospholipids, neutral hpids, and unbound protein fractions in tissues and plasma (fut and fup). The Poulin and Theil models do not take into consideration unbound proteins. 

---