Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.6.3.44 (P-glycoprotein)
 13,344 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pitavastatin has been designed as a synthetic 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor with a novel cyclopropyl moiety that results in several differences compared to other statins. These include effective inhibition of cholesterol synthesis and increased lipoprotein lipase expression at lower doses than other statins, and significant high-density lipoprotein-cholesterol and apolipoprotein A1-elevating activity that persists with time. The safety, tolerability and pharmacokinetics of pitavastatin and its major metabolite, pitavastatin lactone, have been investigated in a variety of patient groups with similar results, which suggests dosage adjustments are not required for gender, age or race. In healthy subjects, pitavastatin is well tolerated at the approved doses with no serious adverse events. The bioavailability of pitavastatin is, at 60%, higher than that of any other statin and the majority of the bioavailable fraction of an oral dose is excreted unchanged in the bile. The entero-hepatic circulation of unchanged drug contributes to the prolonged duration of action and allows once-daily, any-time dosing. Pitavastatin is only slightly metabolised by cytochrome P450 (CYP) 2C9 and not at all by CYP3A4. Neither pitavastatin nor its lactone form, have inhibitory effects on CYP, and CYP3A4 inhibitors have no effect on pitavastatin concentrations. Moreover, P-glycoprotein-mediated transport does not play a major role in the drug's disposition and pitavastatin does not inhibit P-glycoprotein activity. Pitavastatin is transported into the liver by several hepatic transporters but OATP1B1 inhibitors have relatively little effect on plasma concentrations compared with other statins. In general, interactions, except with multi-transporter inhibitors like ciclosporin, are not clinically significant. Consequently, pitavastatin has minimal drug-food and drug-drug interactions making it a treatment option in the large group of dyslipidaemic people that require multidrug therapy.
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PMID:Pitavastatin - pharmacological profile from early phase studies. 2119 52

Multidrug resistance (MDR) represents the major drawback in chemotherapy. Liposome-based approaches could reverse MDR to some extent through circumventing the active efflux effect of P-glycoprotein. However, the reverse power of liposome is very limited because the nontargeting liposome is inefficient to deliver drugs to tumor actively. Besides, autophagy could reinforce the resistance of tumor cells to the cytotoxicity of intracellular drugs. Here, liposomal doxorubicin (Lipodox) that was conjugated with apolipoprotein A1-apo-Lipodox, was employed in tumor targeting delivery of doxorubicin. In the experiments, apo-Lipodox could enter cells effectively and reverse MDR more efficiently than their nontargeting counterpart. Autophagy occurred in this process and contributed to the survival of tumor cells. Combination use of autophagy inhibitors could enhance the cytotoxicity of apo-Lipodox and reverse drug resistance to a higher degree. We propose that this strategy holds promise to overcome MDR in human cancer.
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PMID:Combination of apolipoprotein A1-modi liposome-doxorubicin with autophagy inhibitors overcame drug resistance in vitro. 2535 72