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Biomedical subjects

Y T Sohn

Publications and source records attributed to Y T Sohn.

5 recordsLinked to original sources
PubMed2000

Characterization of amiodarone metabolites and impurities using liquid chromatography/atmospheric pressure chemical ionization mass spectrometry.

Using the high performance liquid chromatography/atmospheric pressure chemical ionization tandem mass spectrometry (HPLC/APCI-MS/MS) technique, together with established trends from the literature, the structures of metabolites and impurities of amiodarone, an anti-arrhythmic drug, have been assigned. By comparing analyses of products of incubation with rat liver microsomes with controls in which glucose 6-phosphate dehydrogenase was omitted, metabolites could be distinguished from impurities. Structures for the two proposed metabolites and four impurities are proposed.

Amiodarone↗
PubMed2000

Polymorphism of clarithromycin.

It is well recognized that physicochemical properties of drugs are affected by the type of polymorphic crystalline form of drugs. Clarithromycin is known to exist in at least three polymorphic crystalline forms. Since conventional means to obtain the most thermodynamically stable form (Form II) for the antibiotics is known to be associated with a low purity of the stable form, we developed a novel method to improve the purity of the crystalline form by a modification of the preparation process. The new method involved a simple recrystallization of clarithromycin in solvents having 5-12 carbon atoms (e.g., hexane and heptane) or ethers with 4-10 carbon atoms (e.g., isopropyl ether) and, thus, less likely to be associated with the problem in purity of resulting crystal. Differential scanning calorimetry and powder X-ray diffraction were used to compare the crystalline form of the resultant powder with Form II crystal prepared by the conventional method. The crystal prepared by the new method was identical to Form II crystal of the conventional method as evidenced by the lack of the exothermic peak near 110 degrees C in differential calorimetry scan, indicating that Form II crystal could be readily prepared by the new process. Therefore, these data indicated that the improvement in the purity of the Form II crystal for clarithromycin as well as a significant cost reduction is likely by the novel method.

Anti-Bacterial Agents↗
PubMed2000

No effect of water deprivation for 48 hours on the pharmacokiinetics of intravenous tacrolimus in rats.

Because the physiological changes that occur in patients with water deprivation could alter the pharmacokinetics of drugs, the pharmacokinetics of tacrolimus were investigated after 1-min intravenous administration of the drug (1 mg/kg) to control rats and rats with water deprivation for 48 h. In rats with dehydration, kidney function seemed to be impaired slightly. Kidney weight (0.800 versus 0.676% body weight) increased significantly and the renal tissue showed only total and mild tubular dilatation and flattening of tubular epithelial cells based on kidney microscopy. However, hepatic function seemed not to be impaired in rats with dehydration. After intravenous administration of tacrolimus, the pharmacokinetic parameters were not significantly different between two groups of rats and the results were expected since tacrolimus was almost completely metabolized in rats (impaired kidney function could not affect considerably the pharmacokinetics of tacrolimus) and hepatic function was not impaired in rats with dehydration.

Animals↗
PubMedDate not supplied

Pharmacokinetic changes of intravenous tacrolimus in rats with uranyl nitrate-induced acute renal failure.

Because the physiological changes that occur in patients with acute renal failure could alter the pharmacokinetics of the drugs, the pharmacokinetics of tacrolimus were investigated after 1-min intravenous administration of the drug (1 mg kg(-1)) to control rats and rats with uranyl nitrate-induced acute renal failure (rats with U-ARF). The impaired kidney and hepatic functions were observed in rats with U-ARF on the basis of physiological parameters and by microscopy of the tissues. After intravenous infusion of tacrolimus, the total area under the blood concentration-time curve from time zero to time infinity was significantly greater in rats with U-ARF than that in control rats (35.8 versus 29.2 microg min mL(-1)) due to significantly slower total body clearance of tacrolimus (27.9 versus 34.3 mL min(-1) kg(-1)), and this could be due to significantly slower nonrenal clearance (because of impaired hepatic function). The urinary excretion of unchanged tacrolimus was almost negligible for both groups of rats, therefore, effects of kidney impairment on the pharmacokinetics of tacrolimus seemed to be minor.

Acute Kidney Injury↗