start-ver=1.4 cd-journal=joma no-vol=44 cd-vols= no-issue=1 article-no= start-page=96 end-page=102 dt-received= dt-revised= dt-accepted= dt-pub-year=2021 dt-pub=20210101 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Acute Peripheral Inflammation Increases Plasma Concentration of Hypoglycemic Agent Nateglinide with Decreased Hepatic Drug-Metabolizing Activity in Rats en-subtitle= kn-subtitle= en-abstract= kn-abstract=The effects of inflammation on hypoglycemic agents were evaluated in male rats with acute peripheral inflammation (API). Nateglinide (NTG) was utilized as a model compound, since it is a hepatically-metabolized compound and its metabolism is mainly mediated by CYP 2C11 enzyme. In the experiments, rats were subjected to carrageenan injection into their hind paws for API induction, and the plasma concentration profiles of NTG were then examined. In addition, pooled liver microsomes were prepared from control and API rats, and the hepatic drug-metabolizing activity toward NTG and the hepatic expression of CYP2C11 protein were evaluated. It was shown that the plasma concentration of NTG following its intravenous administration decreases at a slower rate in API rats than that in control rats. It was also indicated in the incubation study with the liver microsomes that the hepatic drug-metabolizing activity toward NTG decreases in API rats. Additionally, it was revealed in Western immunoblotting that the hepatic expression of CYP2C11 protein decreases in API rats. These findings suggest that inflammation occurring in peripheral tissues brings about a decrease in hepatic NTG metabolism by suppressing the hepatic expression of CYP2C11 protein, causing an alteration of the plasma concentration profile of NTG with its impaired elimination. en-copyright= kn-copyright= en-aut-name=KojinaMoeko en-aut-sei=Kojina en-aut-mei=Moeko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=SuzukiKeiichiro en-aut-sei=Suzuki en-aut-mei=Keiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=NishiwakiAkane en-aut-sei=Nishiwaki en-aut-mei=Akane kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=AibaTetsuya en-aut-sei=Aiba en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= affil-num=1 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=acute inflammation kn-keyword=acute inflammation en-keyword=CYP2C11 kn-keyword=CYP2C11 en-keyword=hepatic drug metabolism, nateglinide kn-keyword=hepatic drug metabolism, nateglinide END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page=1 end-page=9 dt-received= dt-revised= dt-accepted= dt-pub-year=2019 dt-pub=20190828 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Effects of dexamethasone to reverse decreased hepatic midazolam metabolism in rats with acute renal failure en-subtitle= kn-subtitle= en-abstract= kn-abstract= The inductive effects of dexamethasone on hepatic midazolam metabolism were examined in Wistar rats with acute renal failure (ARF) to clarify whether the ARF-related decrease in the hepatic expression of drug-metabolizing enzymes is caused by an impairment in the translation/polypeptide formation process. ARF was induced with intramuscular glycerol injection. Dexamethasone was orally administered. Pooled liver microsomes from five rats were prepared with ultracentrifugation for each of four groups, namely, control and ARF rats, control rats with dexamethasone treatment and ARF rats with dexamethasone treatment. Hepatic drug-metabolizing activity was examined in an incubation study with the microsomes, where midazolam was employed as a substrate of cytochrome P450 (CYP) 3A enzymes. The hepatic protein and mRNA expressions of CYP3A23/3A1 and 3A2 enzymes were also evaluated. With dexamethasone treatment, the hepatic metabolic rate of midazolam increased 1.4 times in control rats, while it increased 19.6 times in ARF rats, reflecting the greater induction of hepatic protein expressions of CYP3A enzymes in ARF rats than in control rats. The hepatic protein expression process for CYP3A23/3A1 and 3A2 responds well to dexamethasone treatment in ARF rats, indicating that the translation/polypeptide formation process is not impaired in the presence of ARF. en-copyright= kn-copyright= en-aut-name=DoiMasami en-aut-sei=Doi en-aut-mei=Masami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=KajikawaNoriko en-aut-sei=Kajikawa en-aut-mei=Noriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=AibaTetsuya en-aut-sei=Aiba en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= affil-num=1 en-affil= Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil= Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil= Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=Acute renal failure kn-keyword=Acute renal failure en-keyword=CYP3A2 kn-keyword=CYP3A2 en-keyword=dexamethasone kn-keyword=dexamethasone en-keyword=hepatic drug metabolism kn-keyword=hepatic drug metabolism en-keyword=midazolam kn-keyword=midazolam END start-ver=1.4 cd-journal=joma no-vol=29 cd-vols= no-issue=4 article-no= start-page=1027 end-page=1033 dt-received= dt-revised= dt-accepted= dt-pub-year=2014 dt-pub=2014 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Utility of simple suspension method compared to loss of drug using crushing method on tube administration kn-title=粉砕法による経管投与における薬剤量損失に対する簡易懸濁法の有用性についての検討 en-subtitle= kn-subtitle= en-abstract=Objective: In the past, a conventional crushing method was used for the administration of tablets or capsules by tube in patients with dysphagia. However, this method has several problems, such as a loss of the drug amount and tube clogging. Recently, tube administration by a simple suspension method was developed to solve these problems in the conventional crushing method. Methods: In the present study, we investigated to what extent the dosage amount is lost using the simple suspension method compared to crushing method, employing 5 drugs which are frequently administered by tube in Okayama University Hospital. Results: Drug weights of the 5 agents decreased by 70 〜 90% in the grinding and packaging processes because of drug adhesion to the mortar, packaging machine, and drug package paper. The suspension of all drugs using the simple suspension method was uniform, while only the suspension of Warfarin? ground using the crushing method was shown to be showed inhomogeneous, which is expected to lead to a loss of drug. The drug content on assuming clinical a setting after tube passage was compared between the two methods. The recovery of warfarin?, characterized as unstable using the crushing method, was nearly 50%, but loss was prevented by 80% with the use of bags of medicine. For the simple suspension method, the recovery of warfarin? was almost 100%. Conclusion: The results of this study suggest that the simple suspension method is particularly effective for the tube administration of drugs characterized as unstable. kn-abstract=【目的】従来の薬剤経管投与法である粉砕法は薬効の減少につながる薬剤量の損失が指摘されている。そこで粉砕法による薬剤量損失に対する簡易懸濁法の有用性について検討した。 【方法】頻繁に粉砕指示がなされる5種類の薬剤を用いて粉砕・分包による薬物含量減少、薬剤調製時の懸濁性および実際の経管投与を想定した薬物含量について2つの方法を比較した。 【結果】薬剤を粉砕・分包するとそれぞれの薬物含量は減少した。またワーファリン?錠を粉砕して水に溶解すると完全には懸濁せず、小さな塊が生じたが、簡易懸濁法では均一に懸濁した。ワーファリン?錠の経管投与を想定した実験において粉砕法では薬物含量が大幅に減少したが、簡易懸濁法では、ほとんど損失が認められなかった。【結論】簡易懸濁法は粉砕法に比べて薬剤損失の面で有用性が高いことが示唆され、ワーファリン?錠のように安定性が悪い薬剤では特に適正な薬物投与に貢献出来ると考えられる。 en-copyright= kn-copyright= en-aut-name=ZamamiYoshito en-aut-sei=Zamami en-aut-mei=Yoshito kn-aut-name=座間味義人 kn-aut-sei=座間味 kn-aut-mei=義人 aut-affil-num=1 ORCID= en-aut-name=KoyamaToshihiro en-aut-sei=Koyama en-aut-mei=Toshihiro kn-aut-name=小山敏広 kn-aut-sei=小山 kn-aut-mei=敏広 aut-affil-num=2 ORCID= en-aut-name=AibaTetsuya en-aut-sei=Aiba en-aut-mei=Tetsuya kn-aut-name=合葉哲也 kn-aut-sei=合葉 kn-aut-mei=哲也 aut-affil-num=3 ORCID= en-aut-name=AmanoManabu en-aut-sei=Amano en-aut-mei=Manabu kn-aut-name=天野学 kn-aut-sei=天野 kn-aut-mei=学 aut-affil-num=4 ORCID= en-aut-name=AndoTetsuaki en-aut-sei=Ando en-aut-mei=Tetsuaki kn-aut-name=安藤哲信 kn-aut-sei=安藤 kn-aut-mei=哲信 aut-affil-num=5 ORCID= en-aut-name=KurataNaomi en-aut-sei=Kurata en-aut-mei=Naomi kn-aut-name=倉田なおみ kn-aut-sei=倉田 kn-aut-mei=なおみ aut-affil-num=6 ORCID= en-aut-name=NawaHideki en-aut-sei=Nawa en-aut-mei=Hideki kn-aut-name=名和秀起 kn-aut-sei=名和 kn-aut-mei=秀起 aut-affil-num=7 ORCID= en-aut-name=NakuraHironori en-aut-sei=Nakura en-aut-mei=Hironori kn-aut-name=名倉弘哲 kn-aut-sei=名倉 kn-aut-mei=弘哲 aut-affil-num=8 ORCID= en-aut-name=KitamuraYoshihisa en-aut-sei=Kitamura en-aut-mei=Yoshihisa kn-aut-name=北村佳久 kn-aut-sei=北村 kn-aut-mei=佳久 aut-affil-num=9 ORCID= en-aut-name=SendoToshiaki en-aut-sei=Sendo en-aut-mei=Toshiaki kn-aut-name=千堂年昭 kn-aut-sei=千堂 kn-aut-mei=年昭 aut-affil-num=10 ORCID= affil-num=1 en-affil= kn-affil=岡山大学大学院 医歯薬学総合研究科 affil-num=2 en-affil= kn-affil=岡山大学大学院 医歯薬学総合研究科 affil-num=3 en-affil= kn-affil=岡山大学大学院 医歯薬学総合研究科 affil-num=4 en-affil= kn-affil=兵庫医療大学 薬学部 affil-num=5 en-affil= kn-affil=吉備高原ルミエール病院 薬剤科 affil-num=6 en-affil= kn-affil=昭和大学 薬学部 affil-num=7 en-affil= kn-affil=岡山大学病院 薬剤部 affil-num=8 en-affil= kn-affil=岡山大学大学院 医歯薬学総合研究科 affil-num=9 en-affil= kn-affil=岡山大学病院 薬剤部 affil-num=10 en-affil= kn-affil=岡山大学病院 薬剤部 en-keyword=簡易懸濁法 (simple suspension method) kn-keyword=簡易懸濁法 (simple suspension method) en-keyword=経管投与 (tube administration) kn-keyword=経管投与 (tube administration) en-keyword=薬剤量の損失 (loss of drug amount) kn-keyword=薬剤量の損失 (loss of drug amount) END start-ver=1.4 cd-journal=joma no-vol=343 cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2008 dt-pub=20080522 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Evaluation of intramuscular lateral distribution profile of topically administered acetaminophen in rats en-subtitle= kn-subtitle= en-abstract= kn-abstract=

To clarify to what extent topically administered drug molecules horizontally permeate into tissues surrounding the administration site, the intramuscular lateral concentration profile of acetaminophen was investigated in vivo using the microdialysis method in rats. When acetaminophen was intramuscularly administered for 6 hr in a pinpoint manner at a constant rate of 3 μg/min, it was clearly detected in the muscle surrounding the administration site, being 17.5 μg/ml when measured at a 2 mm distance from the administration site. The concentration in the muscle was decreased as the distance increased, and those measured at 5 mm and 40 mm were 0.35 μg/ml and 0.09 μg/ml, respectively. In addition, it was shown that the concentration in the muscle at 40 mm reflected the compound’s concentration in plasma, but not the compound’s horizontal permeation from the administration site. With these observations, the intramuscular distribution profile of acetaminophen was numerically characterized according to Fick’s law. As a result, it was revealed that horizontal permeation is the primary process accountable for the increased intramuscular concentration only in the area adjacent to the administration site, and the radius of the adjacent area was calculated to be 5.80 mm for acetaminophen.

en-copyright= kn-copyright= en-aut-name=KurosakiYuji en-aut-sei=Kurosaki en-aut-mei=Yuji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=TagawaMasahiro en-aut-sei=Tagawa en-aut-mei=Masahiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OmotoAkiho en-aut-sei=Omoto en-aut-mei=Akiho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=SuitoHiroshi en-aut-sei=Suito en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KomoriYukiko en-aut-sei=Komori en-aut-mei=Yukiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KawasakiHiromu en-aut-sei=Kawasaki en-aut-mei=Hiromu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=AibaTetsuya en-aut-sei=Aiba en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil= kn-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University affil-num=2 en-affil= kn-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University affil-num=3 en-affil= kn-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University affil-num=4 en-affil= kn-affil=Graduate School of Environmental Sciences, Okayama University affil-num=5 en-affil= kn-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences affil-num=6 en-affil= kn-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University affil-num=7 en-affil= kn-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University en-keyword=Microdialysis kn-keyword=Microdialysis en-keyword=Intramuscular concentration profile kn-keyword=Intramuscular concentration profile en-keyword=Drug disposition kn-keyword=Drug disposition en-keyword=Acetaminophen kn-keyword=Acetaminophen en-keyword=Pharmacokinetics kn-keyword=Pharmacokinetics en-keyword=Drug delivery kn-keyword=Drug delivery END