Weak acids, drugs

Increasing the gastric pH, which causes a decrease in absorption of weakly acidic drugs and results in a decreased drug effect (eg, digoxin, phenytoin, chlorpromazine, and isoniazid)... 

Ketoprofen, a weak-acid drug, with a pKa 4.12 (25°C, 0.01 M ionic strength), was selected to illustrate Eqs. (7.20) and (7.21) in a series of simulation calculations, as shown in Fig. 7.16. The membrane-buffer apparent partition coefficients /(piii were calculated at various pH values, using the measured constants from... 

Twenty weakly acidic drugs, including niclosamide, were determined by a nonaqueous catalytic thermometric titration method. Catalysis of the anionic polymerization of acetonitrile was used for endpoint indication. The solvent used was a mixture of acetonitrile and dimethylformamide or pyridine, and the titrant was sodium methoxide, potassium hydroxide, tertiary butanol, or tertiary butanol-sodium nitrite. Recoveries, limits of detection and relative standard deviations were tabulated [31]. 

CYP2C9 is the major CYP2C enzyme expressed in human liver [35] and plays a major role in the metabolism of numerous therapeutics including many weak acidic drugs such as the nonsteroidal anti-inflammatory compounds (e.g. flurbiprofen) [36] and antidiabetics (e.g. tolbutamide) [37]. In addition, CYP2C9 also metabolizes (S)-warfarin [38], lornoxicam [39] and phenytoin [37]. 

For even less soluble, weak acid drugs, the situation is not so simple, because the solubility even in biorelevant media is very low. A typical example is troglitazone, an antidiabetic... 

Weakly acidic drugs will be less ionized in the stomach and therefore penetrate membranes more readily in this organ while weakly basic drugs will be less ionized and therefore more readily absorbed in the small intestine. 

D) Decreasing renal tubular fluid pH will increase eliminafion of weakly acidic drugs. 

Aceiazolamide, the best example of this class of diuretics, is rarely used as a diuretic since the introduction of the thiazides. its main use is for the treatment of glaucoma and sonic minor uses. e.g.. Tor the alkitlini/alion of the urine to accelerate the renal excretion uf some weak acidic drugs, and for the prevention of acute high altitude mountain sickness. 

Dissolution rate is a function of the drug concentration at the site of absorption, which is directly proportional to the saturation solubility of the drug. For a weakly acidic drug, increasing the pH increases the extent and rate, at which the drug dissolves, which in turn, can signiLcantly inLuence the absorption behavior of the drug. 

Assuming a dissociation of a weak acid drug according to the general reaction ... 

Rhodes et al (31) determined a mixture containing ace-tylsalicylic acid, acetaminophen and salicylamide, potentiometrically by non-aqueous titration. The tit-rant was 0.1 N tetrabutylammonium hydroxide in benzene/ methanol mixture and the titration solvent was dimethyl-formamide. The difference in the pKa values for these weak acidic drugs (aspirin pKa 3-5, acetaminophen pKa 8.31) was sufficient to permit useful differentiation. 

Strongly and weakly acidic drugs (typically cannabinoids) can be separated by using a C8 column with acetonitrile-phosphate at pH 8 [177] which can, with some limitations, also be used for weakly basic and neutral analytes. 

As shown in Equation (3.49d) and Equation (3.110), the solubility and partition coefficients are dependent on the pH of solution. For weak acid drugs, the solubility increases with the increase in pH, whereas the partition coefficient decreases with the increase in pH. One may postulate that the product of solubility and partition coefficient is independent of pH because the pH effect of the solubility counterbalances out that of the partition coefficient as ... 

In this system, weakly acidic drugs (barbiturates), as well as neutral and basic drugs, are extracted together at pH 9. Phenobarbitone extraction is poor (recovery approximately 20%), but is still sufficient to allow detection of the drug in dependent patients. 

HPLC as a comparative technique has a number of advantages, including the fact that it does not require the analyte to be volatile, it does not require any pre-treatment of the sample prior to analysis, such as derivatization, it can be automated and can be used quantitatively. The HPLC technique used is a reversed-phase system and employs ion-suppression. Cannabinoids are weakly acidic drugs due to the presence of phenolic moieties on the aromatic rings. 

A number of proteins are commercially available as CSPs including a-acid glycoproteins (AGP, the major plasma binding protein for basic drugs), human serum albumin (HSA, the major plasma binding protein for weakly acidic drugs), bovine serum albumin (BSA), ovomucoid (OVM), and cellobiohydro-lase (CBH) [12]. The proteins are bonded to silica and utilized in reversed-phase mode with an aqueous buffer/organic modifier eluent. Mobile-phase... 

Additionally, since the stomach is one of the desired absorption sites for weakly acidic drugs, there should be no lag time in drug release from the GRDDS. Ideally, this type of delivery system is required for loop diuretics, such as furosemide and piretanide, in which the release of a certain amount of drug in the stomach is desired to obtain more balanced bioavailability. Consequently, this property prompted the development of floating systems for these acidic drugs. ... 

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