※一部利用できない機能があります
| 1.
図書 |
図書
|
Charles D. Ciccone
|
||||
| 2.
図書 |
図書
|
editor-in-chief, Laurence L. Brunton ; editors, Randa Hilal-Dandan, Björn C. Knollmann
|
||||
| 3.
図書 |
図書
|
Robin L. Southwood, Virginia H. Fleming, Gary Huckaby
|
||||
| 4.
図書 |
図書
|
[editors], Michael E. Burton ... [et al.]
|
||||
| 5.
図書 |
図書
|
edited by Micaela B. Reddy ... [et al.]
|
||||
| 6.
論文 |
論文
|
Nakano, Masataka ; Nakajima, Miki ; 中嶋, 美紀
概要:
金沢大学医薬保健研究域薬学系<br />RNA editing is a post-transcriptional process that alters the nucleotide sequence of RNA transcripts
…
to generate transcriptome diversity. Among the various types of RNA editing, adenosine-to-inosine (A-to-I) RNA editing is the most frequent type of RNA editing in mammals. Adenosine deaminases acting on RNA (ADAR) enzymes, ADAR1 and ADAR2, convert adenosines in double-stranded RNA structures into inosines by hydrolytic deamination. Inosine forms a base pair with cytidine as if it were guanosine; therefore, the conversion may affect the amino acid sequence, splicing, microRNA targeting, and miRNA maturation. It became apparent that disrupted RNA editing or abnormal ADAR expression is associated with several diseases including cancer, neurological disorders, metabolic diseases, viral infections, and autoimmune disorders. The biological significance of RNA editing in pharmacokinetics/pharmacodynamics (PK/PD)-related genes is starting to be demonstrated. The authors conducted pioneering studies to reveal that RNA editing modulates drug metabolism potencies in the human liver, as well as the response of cancer cells to chemotherapy agents. Awareness of the importance of RNA editing in drug therapy is growing. This review summarizes the current knowledge on the RNA editing that affects the expression and function of drug response-related genes. Continuing studies on the RNA editing that regulates pharmacokinetics/pharmacodynamics would provide new beneficial information for personalized medicine. © 2017 Elsevier Inc.<br />Embargo Period 12 months
続きを見る
|
||||
| 7.
論文 |
論文
|
Tsuji, Akira
概要:
金沢大学薬学部<br />金沢大学大学院自然科学研究科分子作用学<br />A comprehensive list of drug transporters has recently become available as a resul
…
t of extensive genome analysis. Membrane transporters play important roles in determining the pharmacokinetic aspects of intestinal absorption, tissue distribution, and the urinary and biliary excretions of a wide variety of therapeutic drugs. The identification and characterization of transporters responsible for the transfer of nutrients and xenobiotics, including drugs, is expected to provide a scientific basis for understanding drug disposition, as well as the molecular mechanisms of drug-drug/drug-food/drug-protein interactions and inter-individual/inter-species differences. This review focuses on the influence of transporters on the pharmacokinetics of β-lactam antibiotics, new quinolones, and other antimicrobial agents, as well as focusing on the drug-drug interactions associated with transporter-mediated uptake from the small intestine and transporter-mediated elimination from the kidney and liver. © 2006 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases.
続きを見る
|
||||
| 8.
論文 |
論文
|
Hirosawa, Iori ; Ishikawa, Mai ; Ogino, Mio ; Ito, Hiroshi ; Hirao, Takuya ; Yamada, Harumi ; Asahi, Mariko ; Kotaki, Hajime ; Sai, Yoshimichi ; Miyamoto, Ken-ichi
概要:
Clenbuterol is a long-acting β2-adrenoceptor agonist and bronchodilator that is used for the treatment of asthma, but th
…
e desired activities reside almost exclusively in the (-)-R-enantiomer. This study examined enantioselectivity in the disposition of clenbuterol following administration of clenbuterol racemate to rats. Concentrations of clenbuterol enantiomers in plasma, urine and bile were determined by LC-MS/MS assay with a Chirobiotic T column. This method was confirmed to show high sensitivity, specificity and precision, and clenbuterol enantiomers in 0.1ml volumes of plasma were precisely quantified at concentrations as low as 0.25ng/ml. The pharmacokinetic profiles of clenbuterol enantiomers following intravenous and intraduodenal administration of clenbuterol racemate (2mg/kg) in rats were significantly different. The distribution volume of (-)-R-clenbuterol (9.17l/kg) was significantly higher than that of (+)-S-clenbuterol (4.14l/kg). The total body clearance of (-)-R-clenbuterol (13.5ml/min/kg) was significantly higher than that of the (+)-S-enantiomer (11.5ml/min/kg). An in situ absorption study in jejunal loops showed no difference in the residual amount between the (-)-R- and (+)-S-enantiomers. Urinary clearance was the same for the two enantiomers, but biliary excretion of (-)-R-clenbuterol was higher than that of the (+)-S-enantiomer. The fractions of free (non-protein-bound) (-)-R- and (+)-S-clenbuterol in rat plasma were 48.8% and 33.1%, respectively. These results indicated that there are differences in the distribution and excretion of the clenbuterol enantiomers, and these may be predominantly due to enantioselective protein binding. © 2013 John Wiley & Sons, Ltd.<br />発行後1年より全文公開
続きを見る
|
||||
| 9.
論文 |
論文
|
Ishizaki, Junko ; Tsuda, Tomoko ; Suga, Yukio ; Ito, Satsuki ; Arai, Kunizo ; Sai, Yoshimichi ; Miyamoto, Ken-ichi
概要:
Changes of mycophenolic acid (MPA) pharmacokinetics with aging were investigated in rats. We also compared the effect of
…
concomitant amoxicillin/clavulanate combination (CVA/AMPC) on the pharmacokinetics of MPA in 4-week-old and 12-week-old rats (the package insert of CVA/AMPC warns of possible interaction with MPA). Four-week-old rats showed a 1.4-fold higher total body clearance of MPA and a lower volume of distribution of MPA (65%), compared to the values in 12-week-old rats. However, the difference in MPA pharmacokinetics disappeared when enterohepatic circulation was eliminated by bile duct cannulation (BDC). Concomitant CVA/AMPC significantly reduced plasma MPA concentration in intact rats of both age groups, and the age-dependent difference of MPA pharmacokinetics was no longer apparent. The effect of CVA/AMPC was not seen in rats that had undergone BDC, suggesting that the drug-drug interaction can be attributed to inhibition of enterohepatic circulation by CVA/AMPC. These results indicate that the aging-related alteration of MPA pharmacokinetics is a consequence of immature enterohepatic circulation in 4-week-old rats. Higher doses of MPA may be necessary in juveniles. © 2012 The Pharmaceutical Society of Japan.
続きを見る
|
||||
| 10.
論文 |
論文
|
Kato, Sayaka ; Kato, Yukio ; Nakamura, Tadakatsu ; Sugiura, Tomoko ; Kubo, Yoshiyuki ; Deguchi, Yoshiharu ; Tsuji, Akira
概要:
金沢大学医薬保健研究域薬学系<br />Carnitine/organic cation transporter 2 (OCTN2) recognizes various cationic compounds as substrates i
…
n vitro, but information on its pharmacokinetic role in vivo is quite limited. This paper demonstrates altered tissue distribution of the OCTN2 substrate pyrilamine in juvenile visceral steatosis (jvs) mice, which have a hereditary defect of the octn2 gene. At 30 min after intravenous injection of pyrilamine, the tissue-to-plasma concentration ratio (K p) in the heart and pancreas was higher, whereas the Kp in kidney and testis was lower in jvs mice compared with wild-type mice. Pyrilamine transport studies in isolated heart slices confirmed higher accumulation, together with lower efflux, of pyrilamine in the heart of jvs mice. The higher accumulation in heart slices of jvs mice was abolished by lowering the temperature, by increasing the substrate concentration, and in the presence of other H1 antagonists or another OCTN2 substrate, carnitine, suggesting that OCTN2 extrudes pyrilamine from heart tissue. On the other hand, the lower distribution to the kidney of jvs mice was probably due to down-regulation of a basolateral transporter coupled with OCTN2, because, in jvs mice, (i) the Kp of pyrilamine in kidney assessed immediately after intravenous injection (∼1 min) was also lower, (ii) the urinary excretion of pyrilamine was lower, and (iii) the uptake of pyrilamine in kidney slices was lower. The renal uptake of pyrilamine was saturable (K m∼236 μM) and was strongly inhibited by cyproheptadine, astemizole, ebastine and terfenadine. The present study thus indicates that genetic deficiency of octn2 alters pyrilamine disposition tissue-dependently. Copyright © 2009 John Wiley & Sons, Ltd.
続きを見る
|
