The effect of morbid obesity on morphine glucuronidation.


:The purpose of the present work was to study the change in morphine metabolic ratio in obese subjects before and after Roux-en-Y Gastric Bypass (RYGB) and to identify clinical and/or biological factors associated with this change. The pharmacokinetics (PK) of oral morphine (30mg), morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) was performed in patients before (n=25; mean BMI=43.2 (35.4-61.9)kg/m2), 7-15days (n=16) and 6 months after RYGB (n=19; mean BMI=32.3 (25.4-46.0)kg/m2). Morphine Cmax and AUC0-inf were significantly increased and morphine Tmax significantly shortened at 6 months after RYGB compared with preoperative data, indicating an important increase in the rate and extent of morphine absorption. The morphine metabolic ratio 0-inf M3G+M6G/Morphine, decreased significantly from the preoperative to 6 months postoperative period with an average of -26% (range -74%; +21%; p=0.004), but not in the immediate post-operative period. The change in morphine metabolic ratio was associated with a change in BMI, fat mass in kg, and triglyceride levels (rho=0.5, p≤0.04). The degree of change in several markers of low-grade inflammation, or the level of liver steatosis and fibrosis before surgery, was not associated with the change in morphine metabolic ratios. Our findings indicate that RYGB-induced weight loss significantly decreases morphine metabolic ratio, arguing for an effect of morbid obesity on glucuronidation. With glucuronide exposure at 6 months similar to preoperative values, a higher morphine AUC0-inf should encourage reducing morphine dosage in patients undergoing RYGB and chronically receiving immediate-release oral morphine.


Pharmacol Res


Pharmacological research


Lloret-Linares C,Luo H,Rouquette A,Labat L,Poitou C,Tordjman J,Bouillot JL,Mouly S,Scherrmann JM,Bergmann JF,Declèves X




Has Abstract


2017-04-01 00:00:00












  • Increased potency of some substituted short peptide analogues in comparison to galanin(1-15)-NH(2)in rat fundus strips.

    abstract::The activity of short porcine galanin (Gal) analogues was tested in vitro using rat gastric fundus strips. The peptides contracted longitudinal smooth muscle in a concentration-dependent manner with the following order of potency: Gal(1-29) >[Cit(14)]Gal(1- 15) >[Asp(14)]Gal(1- 15) >[Dab(14)]Gal(1- 15) >[Nle(14)] Gal(...

    journal_title:Pharmacological research

    pub_type: 杂志文章


    authors: Korolkiewicz RP,Konstański Z,Rekowski P,Ruczyński J,Szyk A,Dabkowski J,Ujda M,Korolkiewicz KZ,Petrusewicz J

    更新日期:2001-07-01 00:00:00

  • Purinergic P2Y6 receptors: A new therapeutic target of age-dependent hypertension.

    abstract::Aging has a remarkable effect on cardiovascular homeostasis and it is known as the major non-modifiable risk factor in the development of hypertension. Medications targeting sympathetic nerve system and/or renin-angiotensin-aldosterone system are widely accepted as a powerful therapeutic strategy to improve hypertensi...

    journal_title:Pharmacological research

    pub_type: 杂志文章,评审


    authors: Sunggip C,Nishimura A,Shimoda K,Numaga-Tomita T,Tsuda M,Nishida M

    更新日期:2017-06-01 00:00:00

  • Anti-apoptotic effect of succinyl gelatine in a liver ischaemia-reperfusion injury model (Bcl-2, Bax, Caspase 3)?

    abstract::Apoptosis of tissues may contribute to ischaemia-reperfusion injury. The aim of the present study was to determine whether administration of a colloid solution would prevent apoptosis after liver ischaemia-reperfusion. New Zealand rabbits, weighing 1.5-2 kg, were randomized to receive either 4% SG (20 ml kg (-1)h(-1) ...

    journal_title:Pharmacological research

    pub_type: 杂志文章


    authors: Altunkan A,Aydin O,Ozer Z,Colak T,Bilgin E,Oral U

    更新日期:2002-06-01 00:00:00

  • Pharmacological intervention of early neuropathy in neurodegenerative diseases.

    abstract::Extensive studies have reported the significant roles of numerous cellular features and processes in properly maintaining neuronal morphology and function throughout the lifespan of an animal. Any alterations in their homeostasis appear to be strongly associated with neuronal aging and the pathogenesis of various neur...

    journal_title:Pharmacological research

    pub_type: 杂志文章,评审


    authors: Kwon MJ,Kim JH,Kim T,Lee SB

    更新日期:2017-05-01 00:00:00

  • Vigabatrin does not affect the intestinal absorption of phenytoin in rat duodeno-jejunal loops in situ.

    abstract::The antiepileptic drug vigabatrin (GVG) is known to decrease significantly the serum concentration of concurrently administered phenytoin (PHT) in epileptic patients. To assess a possible mechanism for this interaction, the effect of GVG on the intestinal absorption of PHT was investigated by means of circulation expe...

    journal_title:Pharmacological research

    pub_type: 杂志文章


    authors: Tonini M,Gatti G,Manzo L,Olibet G,Coccini T,Perucca E

    更新日期:1992-09-01 00:00:00

  • Effect of nimodipine on systemic, renal, and cerebral haemodynamics after a mild hypoxic-ischaemic insult in newborn piglets.

    abstract::Because many Ca2+ channel blocking agents are known to cause adverse systemic effects, in this study we tested the haemodynamic side effects of nimodipine with and without a mild hypoxic-ischaemic (HI) insult in a newborn piglet model. Fifteen min after completing a brief period of asphyxia we gave i.v. nimodipine as ...

    journal_title:Pharmacological research

    pub_type: 杂志文章


    authors: Raju TN,John E,Shankararao R,Fornell L,Vasa R,Abu-Harb M

    更新日期:1996-01-01 00:00:00

  • The effect of manganese chloride on gentamicin-induced nephrotoxicity in rats.

    abstract::The aim of this study was to investigate the effects of manganese chloride on gentamicin-induced nephrotoxicity in rats. Thirty-six adult Wistar Albino rats were divided into six equal groups. They were injected with gentamicin sulfate (100 mg kg(-1) per day i.p.) and manganese chloride (2 or 20 mg kg(-1) per day i.p....

    journal_title:Pharmacological research

    pub_type: 杂志文章


    authors: Ateşşahin A,Karahan I,Yilmaz S,Ceribaşi AO,Princci I

    更新日期:2003-12-01 00:00:00

  • More than just an enzyme: Dipeptidyl peptidase-4 (DPP-4) and its association with diabetic kidney remodelling.

    abstract:PURPOSE OF THE REVIEW:This review article discusses recent advances in the mechanism of dipeptidyl peptidase-4 (DPP-4) actions in renal diseases, especially diabetic kidney fibrosis, and summarizes anti-fibrotic functions of various DPP-4 inhibitors in diabetic nephropathy (DN). RECENT FINDINGS:DN is a common complica...

    journal_title:Pharmacological research

    pub_type: 杂志文章,评审


    authors: Gupta S,Sen U

    更新日期:2019-09-01 00:00:00

  • Targeting nanoparticles to cancer.

    abstract::Nanotechnology applications in medicine, termed as nanomedicine, have introduced a number of nanoparticles of variable chemistry and architecture for cancer imaging and treatment. Nanotechnology involves engineering multifunctional devices with dimensions at the nanoscale, similar dimensions as those of large biologic...

    journal_title:Pharmacological research

    pub_type: 杂志文章,评审


    authors: Wang M,Thanou M

    更新日期:2010-08-01 00:00:00

  • The influence of divalent cations on the analgesic effect of opioid and non-opioid drugs.

    abstract::It is generally accepted that divalent cations are involved in the nociceptive pathway. The effect of systemic co-administration of magnesium sulfate and calcium channel blockers (nifedipine, verapamil) on the analgesic effect of opioid (mixed mu/kappa: butorphanol) and non-opioid drugs (paracetamol) was investigated....

    journal_title:Pharmacological research

    pub_type: 杂志文章


    authors: Assi AA

    更新日期:2001-06-01 00:00:00

  • Evidence for a role of nitric oxide in the mediation of antiproliferative UVA effects in keratinocytes.

    abstract::Using cultured human keratinocytes, the present study investigates the role of nitric oxide (NO) in the mediation of the antiproliferative effects of ultraviolet light A (UVA). UVA treatment of cells (3-21 J cm (-2)) caused a time- and dose-dependent increase in nitrite formation in a micromolar range. This effect was...

    journal_title:Pharmacological research

    pub_type: 杂志文章


    authors: Podhaisky HP,Klapperstück T,Riemschneider S,Wohlrab W

    更新日期:2002-03-01 00:00:00

  • Harnessing ionic mechanisms to achieve disease modification in neurodegenerative disorders.

    abstract::Progressive neuronal death is the key pathogenic event leading to clinical symptoms in neurodegenerative disorders (NDDs). Neuroprotective treatments are virtually unavailable, partly because of the marked internal heterogeneity of the mechanisms underlying pathology. Targeted neuroprotection would require deep mechan...

    journal_title:Pharmacological research

    pub_type: 杂志文章,评审


    authors: Masi A,Narducci R,Mannaioni G

    更新日期:2019-09-01 00:00:00

  • Drugs preventing Na+ and Ca2+ overload.

    abstract::Cardiac intracellular Na+and Ca2+homeostasis is regulated by the concerted action of ion channels, pumps and exchangers. The Na+, K+-ATPase produces the electrochemical concentration gradient for Na+, which is the driving force for Ca2+removal from the cytosol via the Na+/Ca2+exchange. Reduction of this gradient by in...

    journal_title:Pharmacological research

    pub_type: 杂志文章,评审


    authors: Ravens U,Himmel HM

    更新日期:1999-03-01 00:00:00

  • N3,N7-diaminophenothiazinium derivatives as antagonists of α7-nicotinic acetylcholine receptors expressed in Xenopus oocytes.

    abstract::Derivatization of phenothiazine (PTZ, 1) has been a commonly used method to develop drugs with various pharmacological properties. In the present study, a series of PTZ derivatives 1-11 were investigated on the inhibition of the cloned α7 subunit of the human nicotinic acetylcholine receptor (α7-nAChR) expressed in Xe...

    journal_title:Pharmacological research

    pub_type: 杂志文章


    authors: Sadek B,Ashoor A,Al Mansouri A,Lorke DE,Nurulain SM,Petroianu G,Wainwright M,Oz M

    更新日期:2012-09-01 00:00:00

  • Isobolographic analysis of the antinociceptive interactions of clonidine with nonsteroidal anti-inflammatory drugs.

    abstract::The present study was undertaken to characterize the interactions between nonsteroidal anti-inflammatory drugs and the alpha(2)-adrenoceptor agonist clonidine in an acute nociceptive test. The writhing test was selected as a model of acute visceral pain. Isobolograms were constructed to assess the interactions of clon...

    journal_title:Pharmacological research

    pub_type: 杂志文章


    authors: Miranda HF,Pinardi G

    更新日期:2004-09-01 00:00:00

  • ATB-346, a novel hydrogen sulfide-releasing anti-inflammatory drug, induces apoptosis of human melanoma cells and inhibits melanoma development in vivo.

    abstract::Inflammation plays a key role in tumor promotion and development. Indeed, cyclooxygenase-2 (COX-2) expression is strongly associated with different types of cancer. An emerging class of compounds with significant anti-inflammatory properties is the hydrogen sulfide-releasing non-steroidal anti-inflammatory drugs (H2S-...

    journal_title:Pharmacological research

    pub_type: 杂志文章


    authors: De Cicco P,Panza E,Ercolano G,Armogida C,Sessa G,Pirozzi G,Cirino G,Wallace JL,Ianaro A

    更新日期:2016-12-01 00:00:00

  • The epicardium as a source of multipotent adult cardiac progenitor cells: Their origin, role and fate.

    abstract::Since the regenerative capacity of the adult mammalian heart is limited, cardiac injury leads to the formation of scar tissue and thereby increases the risk of developing compensatory heart failure. Stem cell therapy is a promising therapeutic approach but is facing problems with engraftment and clinical feasibility. ...

    journal_title:Pharmacological research

    pub_type: 杂志文章,评审


    authors: Smits AM,Dronkers E,Goumans MJ

    更新日期:2018-01-01 00:00:00

  • alpha-Synuclein: a therapeutic target for Parkinson's disease?

    abstract::Parkinson's disease is a progressive age-related neurodegenerative disease with invariant loss of substantia nigra dopamine neurons and striatal projections. This disorder is well known for the associated motoric symptoms including resting tremor and the inability to initiate movement. However, it is now apparent that...

    journal_title:Pharmacological research

    pub_type: 杂志文章,评审


    authors: Maguire-Zeiss KA

    更新日期:2008-11-01 00:00:00

  • Interactions of gut microbiota with functional food components and nutraceuticals.

    abstract::The human gut is populated by an array of bacterial species, which develop important metabolic and immune functions, with a marked effect on the nutritional and health status of the host. Dietary component also play beneficial roles beyond basic nutrition, leading to the development of the functional food concept and ...

    journal_title:Pharmacological research

    pub_type: 杂志文章,评审


    authors: Laparra JM,Sanz Y

    更新日期:2010-03-01 00:00:00

  • Fenofibrate and dipyridamole treatments in low-doses either alone or in combination blunted the development of nephropathy in diabetic rats.

    abstract::Low-doses of fenofibrate and dipyridamole have pleiotropic renoprotective actions in diabetic rats. This study investigated their combined effect relative to their individual treatments and lisinopril in rats with diabetic nephropathy. Streptozotocin (55mg/kg, i.p., once)-administered diabetic rats were allowed for 10...

    journal_title:Pharmacological research

    pub_type: 杂志文章


    authors: Balakumar P,Varatharajan R,Nyo YH,Renushia R,Raaginey D,Oh AN,Akhtar SS,Rupeshkumar M,Sundram K,Dhanaraj SA

    更新日期:2014-12-01 00:00:00

  • Osteopontin plays a key role in vascular smooth muscle cell proliferation via EGFR-mediated activation of AP-1 and C/EBPβ pathways.

    abstract::Osteopontin (OPN) is known as an active player in the progression of vascular remodeling diseases, however, the precise role in the proliferation of vascular smooth muscle cells (VSMC) is unclear. Thus, this study investigated the role of OPN in VSMC proliferation induced by 4-hydroxynonenal (HNE), and identified the ...

    journal_title:Pharmacological research

    pub_type: 杂志文章


    authors: Lee SJ,Baek SE,Jang MA,Kim CD

    更新日期:2016-06-01 00:00:00

  • Green tea polyphenols produce antidepressant-like effects in adult mice.

    abstract::Recent studies have shown that a higher consumption of green tea leads to a lower prevalence of depressive symptoms in elderly individuals. However, no studies have explored the antidepressant-like effect of green tea in preclinical models of depression. The aim of this study was to investigate the antidepressant-like...

    journal_title:Pharmacological research

    pub_type: 杂志文章


    authors: Zhu WL,Shi HS,Wei YM,Wang SJ,Sun CY,Ding ZB,Lu L

    更新日期:2012-01-01 00:00:00

  • The role of short-chain fatty acids in intestinal barrier function, inflammation, oxidative stress, and colonic carcinogenesis.

    abstract::Short-chain fatty acids (SCFAs), mainly including acetate, propionate, and butyrate, are metabolites produced during the bacterial fermentation of dietary fiber in the intestinal tract. They are believed to be essential factors affecting host health. Most in vitro and ex vivo studies have shown that SCFAs affect the r...

    journal_title:Pharmacological research

    pub_type: 杂志文章,评审


    authors: Liu P,Wang Y,Yang G,Zhang Q,Meng L,Xin Y,Jiang X

    更新日期:2021-01-09 00:00:00

  • Transcriptome profiling of NIH3T3 cell lines expressing opsin and the P23H opsin mutant identifies candidate drugs for the treatment of retinitis pigmentosa.

    abstract::Mammalian cells are commonly employed in screening assays to identify active compounds that could potentially affect the progression of different human diseases including retinitis pigmentosa (RP), a class of inherited diseases causing retinal degeneration with compromised vision. Using transcriptome analysis, we comp...

    journal_title:Pharmacological research

    pub_type: 杂志文章


    authors: Chen Y,Brooks MJ,Gieser L,Swaroop A,Palczewski K

    更新日期:2017-01-01 00:00:00

  • Pharmacological strategies to target oncogenic KRAS signaling in pancreatic cancer.

    abstract::The clear importance of mutated KRAS as a therapeutic target has driven the investigation of multiple approaches to inhibit oncogenic KRAS signaling at different molecular levels. However, no KRAS-targeted therapy has reached the clinic to date, which underlies the intrinsic difficulty in developing effective, direct ...

    journal_title:Pharmacological research

    pub_type: 杂志文章,评审


    authors: Chuang HC,Huang PH,Kulp SK,Chen CS

    更新日期:2017-03-01 00:00:00

  • MicroRNA targeting by quercetin in cancer treatment and chemoprotection.

    abstract::A growing number of evidences from clinical and preclinical studies have shown that dysregulation of microRNA (miRNA) function contributes to the progression of cancer and thus miRNA can be an effective target in therapy. Dietary phytochemicals, such as quercetin, are natural products that have potential anti-cancer p...

    journal_title:Pharmacological research

    pub_type: 杂志文章,评审


    authors: Kim DH,Khan H,Ullah H,Hassan STS,Šmejkal K,Efferth T,Mahomoodally MF,Xu S,Habtemariam S,Filosa R,Lagoa R,Rengasamy KR

    更新日期:2019-09-01 00:00:00

  • Effects of cardio-pulmonary bypass on vancomycin plasma concentration decay.

    abstract::The objective of the study was to investigate possible changes in vancomycin serum levels induced by cardio-pulmonary bypass (CPB). Ten cardiac patients (seven males, three females, aged between 56 and 81), who underwent cardiac surgery requiring CPB, took part in the study. Vancomycin (15 mg kg-1) was intravenously i...

    journal_title:Pharmacological research

    pub_type: 临床试验,杂志文章


    authors: Miglioli PA,Merlo F,Grabocka E,Padrini R

    更新日期:1998-10-01 00:00:00

  • Dementia of Alzheimer's disease and other neurodegenerative disorders--memantine, a new hope.

    abstract::Alzheimer's disease is the fourth largest cause of death for people over 65 years of age. Dementia of Alzheimer's type is the commonest form of dementia, the other two forms being vascular dementia and mixed dementia. At present, the therapy of Alzheimer's disease is aimed at improving both, cognitive and behavioural ...

    journal_title:Pharmacological research

    pub_type: 杂志文章,评审


    authors: Sonkusare SK,Kaul CL,Ramarao P

    更新日期:2005-01-01 00:00:00

  • Antinociceptive effects of the hydrophilic alpha 2-adrenoceptor agonist ST-91 in different test circumstances after intrathecal administration to Wistar rats.

    abstract::The antinociceptive and motor effects of the hydrophilic alpha 2-adrenoceptor agonist ST-91 were studied after intrathecal administration to male Wistar rats in different heat-pain tests and different test settings. Intrathecal administration of ST-91 caused a dose-dependent increase in hind paw licking latency in the...

    journal_title:Pharmacological research

    pub_type: 杂志文章


    authors: Horváth G,Dobos I,Liszli P,Klimscha W,Szikszay M,Benedek G

    更新日期:1997-06-01 00:00:00

  • Gene silencing of receptor-interacting protein 2 protects against cigarette smoke-induced acute lung injury.

    abstract:BACKGROUND AND PURPOSE:Chronic obstructive pulmonary disease (COPD) is characterized by progressive alveolar damage and generally irreversible airflow limitation. Nuclear factor-κB (NF-κB) plays a critical role in COPD pathogenesis. Receptor-interacting protein 2 (Rip2), a 60 kDa adaptor protein, is a positive regulato...

    journal_title:Pharmacological research

    pub_type: 杂志文章


    authors: Dong J,Liao W,Tan LH,Yong A,Peh WY,Wong WSF

    更新日期:2019-01-01 00:00:00