取得学位：博士(薬学)，学位授与番号：博乙第183号，学位授与年月日：平成11年3月25日,学位授与年：199

Ishizaki, Junko

石崎 純子

Kanazawa University Repository for Academic Resources

氏名生年月日本籍学位の種類学位記番号学位授与の日付学位授与の要件石崎純子富山県博士（薬学）博乙第183号平成11年３月25曰論文博士（学位規則第4条第２項）塩基性薬物の脂溶性に基づく細胞内分布機構に関する研究学位授与の題目論文審査委員 （主査）大熊勝治（副査）市村藤雄，辻彰，宮本謙一，横川弘一学位論文要旨AbstmctT11ispaperestablishedaphysiologicalpham】acokineticmodelofbasicdrugsonthebasisoftheirlipophilicity,andtheirpharmacokineticpammeterswercp定dictedinhumanslilomtheregressionequationsbetweentheirlipOphilicityandphannacokineticparametelsmmbbits・ApplicationoftheirpKh,Poctandfbvaluescnabledustoprcdictdispositionkineticsofun1mownbasicdrugsinman・nlispaperalsodescribedthestudiesonthemechanismofsubceUulardistributionoflipophiUcweakbases・AlthoughthetissuedistributionofbasicdmgsappearedtodeclcasewithtimesimplyinparallelwiththeirplasmaConcentration,theirsubceUulardistributioninvarioustissuesexhibitedavalietyofpattems・Basicdrugsweredistributedwidelyinvarioustissues,butwereconcentraにdinlunggranulefraction,wheretheaccumulationwasdependentondmglipophiUcityandlysosomaluptake・Astheplasmaconcentrationofdmgsdecreasedaftermaximumlevcl,thecontributionoflysosomestothesubcellulardistributioninclcased・TheuptakeofbasicdmgsintolysosomesdependedbothoMheintralysosomalpHandonthedruglipophilicity・AsthelipOphilicityofthebasicdrugsincreased,theyaccumulatedmolethanthevaluespredictedfiDmthepHpartitiontheoryandraisedtheintralysosomalpHmorepotenUy,probablyowingtotheirbindingwithlysosomalmembraneswithorwithoutadditionalintralysosomalaggregationmesephenomenashouldbeconsideledasabasisofdmginteractioninclinicaltreatments．－４０９－

塩基性薬物の脂溶性に基づく細胞内分布機構に関する研究

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塩基性薬物の脂溶性に基づく細胞内分布機構に関する研究

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