Differential effects of pravastatin on the pharmacokinetics of paroxetine in normal and diabetic rats

被引：5

作者：

Li, Feng ^{[1
]}

Ling, Zhao-li ^{[1
]}

Wang, Zhong-jian ^{[1
]}

Zhong, Ze-yu ^{[1
]}

Shu, Nan ^{[1
]}

Zhang, Mian ^{[1
]}

Liu, Can ^{[1
]}

Liu, Li ^{[1
]}

Liu, Xiao-dong ^{[1
]}

机构：

[1] China Pharmaceut Univ, Ctr Drug Metab & Pharmacokinet, Nanjing 210009, Jiangsu, Peoples R China

来源：

XENOBIOTICA | 2017年 / 47卷 / 01期

基金：

美国国家科学基金会;

关键词：

Freshly isolated hepatocytes; organic anion-transporting polypeptides; paroxetine; pharmacokinetics; pravastatin; ANION TRANSPORTING POLYPEPTIDE; COA REDUCTASE INHIBITOR; CARDIOVASCULAR-DISEASE; GLUCOSE-HOMEOSTASIS; MEMBRANE FLUIDITY; DRUG-INTERACTIONS; MELLITUS; MECHANISMS; DEPRESSION; EPIDEMIOLOGY;

D O I：

10.3109/00498254.2016.1154999

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

1. Diabetes is often accompanied with depression and hypercholesterolemia. It is possible that paroxetine and pravastatin are co-administered to diabetic patients. The aim of this study was to research the differential effect of pravastatin on plasma exposure of paroxetine in normal and diabetic rats. 2. Pharmacokinetics of paroxetine was investigated following oral administration of paroxetine with and without pravastatin in normal and diabetic rats. Effects of pravastatin on metabolism, intestinal absorption and hepatic uptake of paroxetine were investigated. Activity and expression of hepatic Oatp1 and Oatp2 were also assessed. 3. Pravastatin decreased plasma exposure of paroxetine in normal rats, but increased exposure of paroxetine in diabetic rats. Pravastatin neither affected metabolism nor intestinal absorption of paroxetine. Data from hepatocytes demonstrated that hepatic uptake of paroxetine were involved in Oatp1 and Oatp2. Diabetes suppressed Oatp1 activity and expression, but enhanced Oatp2 activity and expression. Pravastatin stimulated Oatp1 but inhibited Oatp2 activity. 4. We concluded that differential effects of pravastatin on plasma exposure of paroxetine in normal and diabetic rats was partly due to the fact that diabetes suppressed Oatp1 activity and expression but enhanced Oatp2 activity and expression as well as that pravastatin stimulated Oatp1 activity but inhibited Oatp2 activity.

引用

页码：20 / 30

页数：11

共 43 条

[1] The HMG-CoA Reductase Inhibitor Pravastatin Stimulates Insulin Secretion through Organic Anion Transporter Polypeptides [J].

Abe, Michiaki ;

Toyohara, Takafumi ;

Ishii, Akiko ;

Suzuki, Takehiro ;

Noguchi, Naoya ;

Akiyama, Yasutoshi ;

Shiwaku, Hiromi O. ;

Nakagomi-Hagihara, Rie ;

Zheng, Guodong ;

Shibata, Eisuke ;

Souma, Tomokazu ;

Shindo, Tomohiko ;

Shima, Hirohito ;

Takeuchi, Yoichi ;

Mishima, Eikan ;

Tanemoto, Masayuki ;

Terasaki, Tetsuya ;

Onogawa, Tohru ;

Unno, Michiaki ;

Ito, Sadayoshi ;

Takasawa, Shin ;

Abe, Takaaki .

DRUG METABOLISM AND PHARMACOKINETICS, 2010, 25 (03) :274-282

[2] Co-Medication of Pravastatin and Paroxetine-A Categorical Study [J].

An, Li ;

Ravindran, Priyadarshini P. ;

Renukunta, Swetha ;

Denduluri, Srinivas .

JOURNAL OF CLINICAL PHARMACOLOGY, 2013, 53 (11) :1212-1219

[3] The prevalence of comorbid depression in adults with diabetes - A meta-analysis [J].

Anderson, RJ ;

Freedland, KE ;

Clouse, RE ;

Lustman, PJ .

DIABETES CARE, 2001, 24 (06) :1069-1078

[4] Active intestinal absorption of fluoroquinolone antibacterial agent ciprofloxacin by organic anion transporting polypeptide, Oatp1a5 [J].

Arakawa, Hiroshi ;

Shirasaka, Yoshiyuki ;

Haga, Makoto ;

Nakanishi, Takeo ;

Tamai, Ikumi .

BIOPHARMACEUTICS & DRUG DISPOSITION, 2012, 33 (06) :332-341

[5] Effects of pravastatin on obesity, diabetes, and adiponectin in diet-induced obese mice [J].

Araki, Kana ;

Masaki, Takayuki ;

Katsuragi, Isao ;

Kakuma, Tetsuya ;

Yoshimiatsu, Hironobu .

OBESITY, 2008, 16 (09) :2068-2073

[6] Effects of the co-administration of mirtazapine and paroxetine on serotonergic neurotransmission in the rat brain [J].

Besson, A ;

Haddjeri, N ;

Blier, P ;

de Montigny, C .

EUROPEAN NEUROPSYCHOPHARMACOLOGY, 2000, 10 (03) :177-188

[7]

Bourin M, 2001, CNS DRUG REV, V7, P25

[8] Pharmacokinetics of verapamil in diabetic rats induced by combination of high-fat diet and streptozotocin injection [J].

Chen, G. M. ;

Hu, N. ;

Liu, L. ;

Xie, S. S. ;

Wang, P. ;

Li, J. ;

Xie, L. ;

Wang, G. J. ;

Liu, X. D. .

XENOBIOTICA, 2011, 41 (06) :494-500

[9] Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): multicentre randomised placebo-controlled trial [J].

Colhoun, HM ;

Betteridge, DJ ;

Durrington, PN ;

Hitman, GA ;

Neil, HAW ;

Livingstone, SJ ;

Thomason, MJ ;

Mackness, MI ;

Charlton-Menys, V ;

Fuller, JH .

LANCET, 2004, 364 (9435) :685-696

[10]

Damak R., 2013, DEPRESS RES TREAT, V2013

← 1 2 3 4 5 →