The Effect of Ethanol on the Hydrolysis of Ester-Type Drugs by Human Serum Albumin.

Human serum albumin (HSA) has two major ligand-binding sites, sites I and II, and hydrolyzes compounds at both sites. Although the hydrolytic interaction of ester-type drugs with other drugs by HSA has been reported, there are only a few studies concerning the effect of pharmaceutical excipients on the hydrolysis of ester-type drugs by HSA. In the present study, we investigated the effect of ethanol (2 vol%; 345 mM) on the hydrolysis of aspirin, p-nitrophenyl acetate, and olmesartan medoxomil, which are ester-type drugs, with 4 different lots of HSA preparations.

Down-regulation of hepatic CYP3A1 expression in a rat model of indomethacin-induced small intestinal ulcers.

The liver and the small intestine are closely related in the processes of drug absorption, metabolism and excretion via the enterohepatic circulation. Small intestinal ulcers are a serious adverse effect commonly occurring in patients taking nonsteroidal anti-inflammatory drugs. However, the influence of small intestinal ulcers on drug metabolism has not been established.

Differences in Esterase Activity to Aspirin and p-Nitrophenyl Acetate among Human Serum Albumin Preparations.

Human serum albumin (HSA) has two major ligand-binding sites, sites I and II, and also hydrolyzes some compounds at both sites. In the present study, we investigated differences in esterase activity among HSA preparations, and also the effects of warfarin, indomethacin, and naproxen on the hydrolytic activities of HSA to aspirin and p-nitrophenyl acetate. The esterase activities of HSA to aspirin or p-nitrophenyl acetate were measured from the pseudo-first-order formation rate constant (kobs) of salicylic acid or p-nitrophenol by HSA.

Intestinal and hepatic expression of cytochrome P450s and mdr1a in rats with indomethacin-induced small intestinal ulcers.

Background: Non-steroidal anti-inflammatory drugs induce the serious side effect of small intestinal ulcerations (SIUs), but little information is available regarding the consequences to drug metabolism and absorption.

Aim: We examined the existence of secondary hepatic inflammation in rats with indomethacin (INM)-induced SIUs and assessed its relationship to the cytochrome P450 (CYP) and P-glycoprotein (mdr1a), the major drug-metabolizing factors in the small intestine and the liver.

Methods: Gene expression of the CYP family of enzymes and mdr1a was measured with quantitative real-time polymerase chain reaction (qPCR).

Downregulation of CYP3A and P-glycoprotein in the secondary inflammatory response of mice with dextran sulfate sodium-induced colitis and its contribution to cyclosporine A blood concentrations.

CYP3A and P-glycoprotein (P-gp) play important roles in drug metabolism and excretion; however, their functions in pathological conditions remain unclear. Hepatobiliary abnormalities have been described in patients with ulcerative colitis, which may affect drug metabolism and excretion in the liver and small intestine. We examined the functions of CYP3A and P-gp in the liver and small intestine of mice with dextran sodium sulfate (DSS)-induced colitis.

[Controlled release of prednisolone from suppository prepared using powder of pulverized tablet].

Prednisolone suppositories have been used successfully for the treatment of ulcerative colitis in hospital settings. However, the raw material of prednisolone suppository, JP prednisolone powder (JP Powder), was recently removed from the market. Therefore we studied the effects of raw material and suppository base on the release of prednisolone suppository for the purpose of designing a new suppository with similar effects to those of suppository prepared using JP powder (old suppository).

[Quality evaluation of magnesium oxide tablets using acid neutralization test and dissolution test].

For the purpose of quality evaluation of commercially available magnesium oxide (MgO) tablets, we studied their acid neutralization and dissolution behaviors. The dissolution test was carried out by the paddle method in 1st fluid (pH 1.2).

[The quality evaluation of magnesium oxide tablet due to acid neutralization action].

For the purpose of quality evaluation of magnesium oxide (MgO) tablets, we considered the dissolution test method with changes in the pH of the dissolution medium as an indicator and studied the elution behavior of MgO from commercial MgO tablets. We also studied the effects of particle size on the elution rate of MgO from MgO tablets. A dissolution test was carried out using the rotating basket method in 100 ml of the first fluid (pH 1.

[Variance of bioavailability of pharmaceutical preparations and analysis of factors affecting it].

Phenytoin (pulverized powder), mefenamic acid (capsule), and sulpiride (film-coated tablet) are currently available on the Japanese market. For absorption of these drugs from their pharmaceutical preparations, they must disintegrate and dissolve during passage through the gastrointestinal tract. The bioavailability of these drugs differ among different pharmaceutical preparations and even for the same preparation.