Abstract：
:The aim of this study was to document the in vivo transport of everolimus (inhibitor of mTOR) by P-glycoprotein (P-gp), and to investigate the influence of lapatinib (inhibitor of P-gp) on everolimus disposition. Pharmacokinetics of everolimus (0.25mg/kg) has been investigated after oral administration in mdr1a-/1b- mice compared to the wild type. Also, everolimus pharmacokinetics was characterized after oral administration on Swiss mice either alone or after 2 days of pre-treatment of lapatinib (200mg/kg). The influence of lapatinib pre-treatment on intestinal P-gp expression was investigated by Western blot analysis. The non-compartimental analysis was performed using Winonlin professional version 4.1 software (Pharsight, Mountain View, CA). The areas under the plasma concentration-time curve (AUC) were compared using Bailer's method. A significant 1.3-fold increase of everolimus AUC observed in mdr1a-/1b- mice suggested that everolimus is transported in vivo by intestinal P-gp in mice. In addition, a 2.6-fold significant increase of everolimus AUC with lapatinib pre-treatment as compared with the everolimus alone group was noticed. The elimination half-life was comparable (t(1/2)=5.3h vs. t(1/2)=4h). A 38.5% significant decrease of P-gp expression was observed in duodenum segment in lapatinib pre-treated group as compared with control group. In conclusion, lapatinib enhanced everolimus absorption by decreasing intestinal P-gp expression. An inhibition of CYP 450 could not be excluded. These results confirm the necessity of a therapeutic monitoring of everolimus combined with an inhibitor of the P-gp and CYP 450 like lapatinib in a future anti-tumor treatment.
journal_name
Biochem Pharmacoljournal_title
Biochemical pharmacologyauthors
Chu C,Abbara C,Noël-Hudson MS,Thomas-Bourgneuf L,Gonin P,Farinotti R,Bonhomme-Faivre Ldoi
10.1016/j.bcp.2009.02.013subject
Has Abstractpub_date
2009-05-15 00:00:00pages
1629-34issue
10eissn
0006-2952issn
1873-2968pii
S0006-2952(09)00114-2journal_volume
77pub_type
杂志文章abstract：:Rosuvastatin increased vascular endothelial NO and attenuated platelet activation after ischemia-reperfusion in mice; nevertheless, the influence of rosuvastatin on the activation of human platelets and the underlying mechanism has never been investigated. In an in vitro study platelets from 8 healthy donors were incu...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2012.09.011
更新日期：2012-12-15 00:00:00
abstract：:The proinflammatory cytokine interleukin (IL)-18 appears to be involved in the pathogenesis of diseases associated with immunoactivation and inflammation. Consequently, blockage of IL-18 bioactivity by use of IL-18 binding protein (IL-18 BP) is likely a promising therapeutic concept. In the present study, we investiga...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(03)00294-6
更新日期：2003-08-01 00:00:00
abstract：:Isolated rat liver mitochondria have been incubated in the presence of the general anesthetic 2,6-diisopropylphenol (0-100 microM) and the efficiency of oxidative phosphorylation has been evaluated by measuring the respiratory rates, the rates of ATP synthesis or hydrolysis and the magnitude of the transmembrane elect...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(91)90684-w
更新日期：1991-06-21 00:00:00
abstract：:Inflammatory cytokines and human immunodeficiency virus type 1 (HIV-1) gp120 are considered to play an important role in the pathogenesis of HIV-1-associated CNS disorders. These substances are produced predominantly by HIV-1-infected or activated macrophages and microglia in the brain and induce neural cell death. Ce...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(01)00692-x
更新日期：2001-09-15 00:00:00
abstract：:Although it is known that the pathogenic mechanism of Helicobacter pylori involves the stimulated production of interleukin-8 (IL-8) as an inflammatory mediator, the details of the pathway remain unclear. The role of mitogen-activated protein kinase (MAPK) in IL-8 production by H. pylori has been examined in an in vit...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(01)00628-1
更新日期：2001-06-15 00:00:00
abstract：:The anticancer drug cis-diamminedichloroplatinum(II) (cisplatin) has been shown previously to form adducts preferentially within internucleosomal or linker DNA rather than to DNA within the nucleosome. To determine whether other "open" regions of chromatin have an increased affinity for cisplatin, adduct formation wit...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(95)02256-2
更新日期：1996-03-08 00:00:00
abstract：:The ability to transplant human tumors into athymic nude mice allows studies of tumor cells in vivo. However, after s.c. injection the incidence of tumor and metastases in nude mice is frequently low. We have studied the tumorigenicity in nude mice of estradiol (E2)-sensitive breast adenocarcinoma MCF7 cells. Matrigel...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(92)90501-9
更新日期：1992-03-17 00:00:00
abstract：:Treatment of red blood cells with the copper (II) ascorbate system causes increased lipid peroxidation, increased membrane microviscosity, and phospholipid translocation with a concurrent decrease in cytosolic catalase and glutathione peroxidase activities. All these changes are prevented if the cells are treated with...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(99)00277-4
更新日期：2000-02-15 00:00:00
abstract：:Suramin, a drug intensively used in the chemotherapy of African trypanosomiasis and onchocerciasis, is currently being tested in clinical trials for AIDS treatment. Its effects on mitochondrial energy metabolism in mammals were studied. At low concentrations it inhibited ATP synthesis and ATPase activity in submitocho...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(88)90241-9
更新日期：1988-07-01 00:00:00
abstract：:The present study aimed to investigate endothelin-1 (ET-1) receptors in human and swine cardiomyocytes with binding studies using ET(A) and ET(B) selective receptor antagonists (BMS-182874 and BQ-788, respectively). Cell distribution of mRNA expression for ET(A) and ET(B) subtypes was investigated by in situ hybridiza...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(99)00081-7
更新日期：1999-07-15 00:00:00
abstract：:The metabolism of toluene in human liver microsomes and by cDNA-expressed human cytochrome P450s (CYPs) was investigated. Toluene was metabolized mainly to benzyl alcohol and slightly to o- and p-cresol by human liver microsomes. Formation of o-cresol was elevated in microsomes from human livers derived from cigarette...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(96)00652-1
更新日期：1997-02-07 00:00:00
abstract：:The effects of two competitive antagonists and two allosteric ligands on the rate of dissociation of [3H]N-methylscopolamine ([3H]NMS) were studied at atrial muscarinic acetylcholine M2 receptors by the technique of "infinite dilution." The dissociation rate for [3H]NMS, initiated by diluting the incubation mixture in...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(96)00814-3
更新日期：1997-03-21 00:00:00
abstract：:When HL-60 cells were stimulated with histamine, a significant differentiation of the cells toward neutrophils was elicited. Histamine increased phagocytic activity, but it reduced myeloperoxidase activity of HL-60 cells. Histamine-induced differentiation in HL-60 cells was inhibited not only by H2 antagonists, such a...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(92)90375-s
更新日期：1992-09-25 00:00:00
abstract：:Nuclear factor-kappaB (NFKB) is a transcription factor with a pivotal role in inducing genes involved in physiological processes as well as in the response to injury and infection. A model has been proposed whereby the diverse agents that activate NFkappaB do so by increasing oxidative stress within the cell. Activati...
journal_title：Biochemical pharmacology
pub_type： 杂志文章,评审
doi：10.1016/s0006-2952(99)00296-8
更新日期：2000-01-01 00:00:00
abstract：:We studied the effect of DW2282-,[(S)-(+)-4-phenyl-1-[N-(4-aminobenzoyl)-indoline-5-sulfonyl-4,5-dihydro-2-imidazolone].hydrochloride], a newly developed anti-cancer agent, on cell proliferation, cell cycle progression, and induction of apoptosis in human promyelocytic leukemia (HL-60) cells. DW2282, a diarylsulfonylu...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(01)00796-1
更新日期：2001-12-01 00:00:00
abstract：:Only very low levels of peroxidase activity were detected in castrated male hamster kidneys [1.0 +/- 0.8(S.E.) units/g protein], and chronic estrogen administration, either diethylstilbestrol (DES) or 17 beta-estradiol, for 1-5 months did not result in any appreciable increase in this activity. In contrast, hamster li...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(83)90529-4
更新日期：1983-02-01 00:00:00
abstract：:Microsomal epoxide hydrolase (mEH) catalyzes the hydrolysis of epoxide intermediates derived from drugs and environmental chemicals. The response of in vivo (embryo) and in vitro (embryo fibroblast) tests were analyzed using mEH-null and wild-type mice to determine the relative role of maternal and embryonic mEH in th...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(02)00847-x
更新日期：2002-03-15 00:00:00
abstract：:Minocycline is a semisynthetic tetracycline derivative; it has anti-inflammatory and anti-cancer effects distinct from its antimicrobial function. However, the molecular mechanism of minocycline-induced cytotoxicity in non-small cell lung cancer (NSCLC) cells has not been identified. Rad51 plays a central role in homo...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2015.07.025
更新日期：2015-10-01 00:00:00
abstract：:Corticosteroid esters have been encapsulated into intact erythrocytes and used as an intravenous treatment for adjuvant induced arthritis in the rat. The treatment consisted of injections of the encapsulated steroids with the effects monitored for up to 14 days. On an equivalent weight basis both encapsulated cortisol...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(83)90362-3
更新日期：1983-11-15 00:00:00
abstract：:The formyl peptide receptor (FPR) gene family has a complex evolutionary history and comprises eight murine members but only three human representatives. To enable translation of results obtained in mouse models of human diseases, more comprehensive knowledge of the pharmacological similarities/differences between the...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2016.09.004
更新日期：2016-11-01 00:00:00
abstract：:Glimepiride and glibenclamide act apparently in a closely comparable manner upon both insulin and glucagon release. Except for the decreased efficiency of D-glucose in suppressing glucagon release after a prior exposure of the pancreas to the hypoglycemic sulfonylureas, no evidence was obtained to suggest that a posit...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(91)90435-8
更新日期：1991-09-27 00:00:00
abstract：:Inflammatory events are tightly associated with the death caused by Herpes simplex virus 1 (HSV-1) infection of the brain. Heat shock protein 90 (Hsp90) is a molecular chaperone that is stimulated in response to many stressful conditions (e.g., inflammation and hypoxia) and Hsp90 inhibitors are suggested to be potent ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2019.05.003
更新日期：2019-08-01 00:00:00
abstract：:Phenylbutazone (PBZ) is known to inhibit the oriented migration of human polymorphonuclear leukocytes (PMNs) induced by formyl-methionyl-leucyl-phenylalanine (FMLP), and to protect these cells against the deactivation caused by their prior incubation with FMLP. To gain insight into the mechanism of these effects, we m...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(82)90082-x
更新日期：1982-10-01 00:00:00
abstract：:The ability of the fetus to detoxify transplacental drugs and chemicals can be a critical determinant of teratogenesis and developmental toxicity. Developmentally regulated expression of alpha class glutathione S-transferases (GSTs) is of particular interest, since these isozymes have high activity toward peroxidative...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(02)01017-1
更新日期：2002-06-01 00:00:00
abstract：:C-1748 is a DNA-binding agent with potent antitumor activity, especially towards prostate and colon carcinoma xenografts in mice. Here, we elucidated the nature of cellular response of human colon carcinoma HCT8 and HT29 cells to C-1748 treatment, at biologically relevant concentrations (EC(90) and their multiplicity)...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2009.12.012
更新日期：2010-05-01 00:00:00
abstract：BACKGROUND/AIMS:Carnitine palmitoyl-transferase I (CPT I) catalyses the synthesis of long-chain (LC)-acylcarnitines from LC-acyl-CoA esters. It is the rate-limiting enzyme of mitochondrial fatty acid beta-oxidation (FAO) pathway and its activity is regulated by malonyl-CoA. The antiepileptic drug valproic acid (VPA) is...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2009.10.011
更新日期：2010-03-01 00:00:00
abstract：:The human α7 neuronal nicotinic acetylcholine receptor gene (CHRNA7) is a candidate gene for schizophrenia and an important drug target for cognitive deficits in the disorder. Activation of the α7*nAChR, results in opening of the channel and entry of mono- and divalent cations, including Ca(2+), that presynaptically p...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2011.06.018
更新日期：2011-10-15 00:00:00
abstract：:Poly(ADP-ribosylation) consists in the conversion of β-NAD(+) into ADP-ribose, which is then bound to acceptor proteins and further used to form polymers of variable length and structure. The correct turnover of poly(ADP-ribose) is ensured by the concerted action of poly(ADP-ribose) polymerase (PARP) and poly(ADP-ribo...
journal_title：Biochemical pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.bcp.2010.04.022
更新日期：2010-12-15 00:00:00
abstract：:Dihydromyricetin (DMY) is the most abundant flavonoid in Ampelopsis grossedentata possessing many pharmacological activities. But less is known about its protective effect against nonalcoholic steatohepatitis (NASH) in the context of metabolic syndrome. The present study is aimed to evaluate the pharmacological effect...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2020.113927
更新日期：2020-05-01 00:00:00
abstract：:Oxyntomodulin (Oxm) is a hormone which has been shown to exhibit a range of potentially beneficial actions for alleviation of obesity-diabetes. However, exploitation of Oxm-based therapies has been severely restricted due to degradation by the enzyme dipeptidylpeptidase-IV (DPP-IV). Thus, the aim of this study was to ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2010.08.010
更新日期：2010-12-01 00:00:00
