Effect of interleukin 6 on the hepatic metabolism of itraconazole and its metabolite hydroxyitraconazole using primary human hepatocytes.

Abstract:

:A potential cytokine-drug interaction between interleukin 6 (IL-6) and itraconazole (ITZ) was studied using human hepatocytes in primary culture. Cultures from 5 adult males (mean age 42 +/- 15 years) who had not received any medicines known to interact with CYP3A4 were studied. Cultures were exposed to ITZ 500 ng/ml, and the effects of 120 microg/ml cimetidine, 50 ng/ml human IL-6, or IL-6 plus IL-6 receptor antagonist were analyzed for 2, 4, 8, and 12 h. Intracellular ITZ and hydroxyitraconazole concentrations were measured using HPLC and normalized to total cellular protein. Mean intracellular concentrations between groups were compared using one-way Anova (f test; p < 0.10) and corresponding Bonferroni versus control test for multiple comparisons (p < 0.02). Mean intracellular ITZ concentrations between the groups were similar at all time points. Human hepatocytes in primary culture can metabolize ITZ. However, IL-6 did not inhibit hydroxyitraconazole formation, but it may inhibit its subsequent metabolism.

journal_name

Pharmacology

journal_title

Pharmacology

authors

Gubbins PO,Melchert RB,McConnell SA,Franks AM,Penzak SR,Gurley BJ

doi

10.1159/000068401

subject

Has Abstract

pub_date

2003-04-01 00:00:00

pages

195-201

issue

4

eissn

0031-7012

issn

1423-0313

pii

68401

journal_volume

67

pub_type

杂志文章
  • The role of vasopressin suppression in phencyclidine-induced diuresis.

    abstract::Phencyclidine (PCP; 10 mg/kg, s.c.) produced a marked diuresis which occurred without significant changes in solute excretion. This diuresis occurred predominantly within 2 h of PCP injection, and was blocked by pretreatment with vasopressin. The maximum diuresis corresponded temporally to a significant fall in plasma...

    journal_title:Pharmacology

    pub_type: 杂志文章

    doi:10.1159/000137786

    authors: Zerbe RL,Bayorh MA,Quirion R,Kopin IJ

    更新日期:1983-01-01 00:00:00

  • Studies on the mechanism of action of colloidal bismuth subcitrate. I. Interaction with sulfhydryls.

    abstract::The present study was designed to examine the reaction pathway of colloidal bismuth subcitrate (CBS) with thiols. Studies were performed using the monothiol glutathione (GSH), the dithiol dithiothreitol (DTT) and the thiol enzymes papain and H+/K(+)-ATPase. UV-vis spectra showed that CBS forms complexes with GSH and D...

    journal_title:Pharmacology

    pub_type: 杂志文章

    doi:10.1159/000139088

    authors: Beil W,Bierbaum S,Sewing KF

    更新日期:1993-08-01 00:00:00

  • Involvement of the nitric oxide/cyclic guanylate monophosphate pathway in the pilocarpine-induced seizure model in mice.

    abstract::The present study was designed to investigate the involvement of the nitric oxide (NO)/cyclic guanylate monophosphate pathway in pilocarpine-induced seizures in mice. Male Swiss mice (26-32 g) were used as the in vivo model. The following pharmacological tools were utilized: the non-selective NO synthase (NOS) inhibit...

    journal_title:Pharmacology

    pub_type: 杂志文章

    doi:10.1159/000346268

    authors: Vasconcelos Rios ER,Moura Rocha NF,Rodrigues Carvalho AM,Freire Vasconcelos L,Leite Dias M,de Carvalho Lima CN,Soares Lopes K,Cavalcante Melo FH,de França Fonteles MM

    更新日期:2013-01-01 00:00:00

  • The Inhibitory Effect of S-777469, a Cannabinoid Type 2 Receptor Agonist, on Skin Inflammation in Mice.

    abstract::We investigated the effects of S-777469 (1-[[6-Ethyl-1-[4-fluorobenzyl]-5-methyl-2-oxo-1, 2-dihydropyridine-3-carbonyl]amino]-cyclohexanecarboxylic acid), a novel cannabinoid type 2 receptor (CB2) agonist, on 1-fluoro-2,4-dinitrobenzene (DNFB)-induced ear inflammation and mite antigen-induced dermatitis in mice. The o...

    journal_title:Pharmacology

    pub_type: 杂志文章

    doi:10.1159/000455916

    authors: Haruna T,Soga M,Morioka Y,Imura K,Furue Y,Yamamoto M,Hayakawa J,Deguchi M,Arimura A,Yasui K

    更新日期:2017-01-01 00:00:00

  • Effectiveness of zopiclone as a preoperative hypnotic.

    abstract::A controlled, double-blind study was made of the efficacy and safety of a new hypnotic, zopiclone, on the preoperative night's sleep by a Joint Study Unit Group of the anesthesiology departments in 6 national hospitals. The following results were found: (1) zopiclone 7.5 and 10 mg and nitrazepam 10 mg were significant...

    journal_title:Pharmacology

    pub_type: 杂志文章

    doi:10.1159/000137927

    authors: Momose T

    更新日期:1983-01-01 00:00:00

  • Pharmacological characterization of M-II, the major human metabolite of ramelteon.

    abstract::The duration of action of melatonin may be important for improvements in sleep efficiency in insomniacs. Ramelteon, a selective melatonin agonist, is primarily metabolized to the active metabolite M-II, which has a longer half-life and greater systemic exposure than ramelteon. Hence, M-II may contribute significantly ...

    journal_title:Pharmacology

    pub_type: 杂志文章

    doi:10.1159/000362459

    authors: Nishiyama K,Nishikawa H,Kato K,Miyamoto M,Tsukamoto T,Hirai K

    更新日期:2014-01-01 00:00:00

  • Nonmutagenic action of cannabinoids in vitro.

    abstract::Under the specific conditions reported for the separate tests delta9-tetrahydrocannabinol (THC) did not elicit a mutagenic response in microbial and eukaryotic in vitro test systems. THC treatment to histidine auxotrophs of Salmonella typhimurium strains TA 98 (susceptible to frame shift mutation) and TA 100 (suscepti...

    journal_title:Pharmacology

    pub_type: 杂志文章

    doi:10.1159/000136789

    authors: Zimmerman AM,Stich H,San R

    更新日期:1978-01-01 00:00:00

  • Cardioprotective effects of (2S,3R,4S)-N'-benzyl-N"-cyano-N-(3,4-dihydro-2-dimethoxymethyl-3-hydroxy-2-methyl-6-nitro-2H-benzopyran-4-yl)-guanidine (KR-31372) in rats and dogs.

    abstract::The cardioprotective effects of (2S,3R,4S)-N'-benzyl- N"-cyano-N-(3,4-dihydro-2-dimethoxymethyl-3-hydro- xy-2-methyl-6-nitro-2H-benzopyran-4-yl)-guanidine (KR-31372) were evaluated against ischemic/reperfusion injury in isolated rat hearts in vitro and in anesthetized rats and dogs in vivo. In isolated perfused rat he...

    journal_title:Pharmacology

    pub_type: 杂志文章

    doi:10.1159/000074671

    authors: Lee BH,Seo HW,Yoo SE

    更新日期:2004-02-01 00:00:00

  • Evidence of nonlinear pharmacokinetics of methotrexate in the rat.

    abstract::Three doses (0.31, 3.1 and 31 mg/kg) of methotrexate (MTX) were given intravenously to rats. The resulting concentration-time curves in plasma (normalized by dividing the plasma concentration by a multiple of the dose) were not superimposable, indicating nonlinear plasma pharmacokinetics. In liver, kidney, bone marrow...

    journal_title:Pharmacology

    pub_type: 杂志文章

    doi:10.1159/000137723

    authors: Scheufler E

    更新日期:1982-01-01 00:00:00

  • In vitro effects of sennoside on contractile activity and fluid flow in the perfused large intestine of the rat.

    abstract::The effect of sodium rhein on contractile activity and fluid flow in the rat complete large intestine was studied in vitro. Contractile activity was recorded using serosal strain gauges and volume transducers recorded distal fluid flow from the segment. Luminal sodium rhein (1 mM) produced a protracted increase in cae...

    journal_title:Pharmacology

    pub_type: 杂志文章

    doi:10.1159/000139840

    authors: Rumsey RD,Squires PE,Read NW

    更新日期:1993-10-01 00:00:00

  • Effect of carvedilol on renal hemodynamics and renal excretory function in spontaneously hypertensive rats.

    abstract::The effects of the novel antihypertensive agent, carvedilol, on renal hemodynamics and excretory function have been investigated and compared with the effects of labetalol in conscious, spontaneously hypertensive rats. Sustained intravenous infusion of carvedilol or labetalol at a rate of 10 micrograms/kg/min resulted...

    journal_title:Pharmacology

    pub_type: 杂志文章

    doi:10.1159/000138719

    authors: Gellai M,DeWolf R,Ruffolo RR Jr

    更新日期:1990-01-01 00:00:00

  • Lack of reciprocity between opioid and 5-HT3 receptors for antinociception in rat spinal cord.

    abstract::We examined the properties of the drug interaction between morphine and 5-HT(3) receptor antagonist at the spinal level. The nociceptive state was induced by subcutaneously injecting formalin solution (5%, 50 microl) into the hindpaw of the rats. Intrathecal morphine and m-CPBG (5-HT(3) receptor agonist) dose-dependen...

    journal_title:Pharmacology

    pub_type: 杂志文章

    doi:10.1159/000094763

    authors: Yoon MH,Bae HB,Choi JI,Kim SJ,Chung ST,Kim CM

    更新日期:2006-01-01 00:00:00

  • Effects of 2(3)-tert-butyl-4-hydroxyanisole pretreatment on cefpiramide binding to mouse glutathione S-transferases.

    abstract::Binding of cefpiramide (CPM) and other beta-lactam antimicrobial agents to 2(3)-tert-butyl-4-hydroxyanisole (BHA)-induced liver glutathione (GSH) S-transferases (EC 2.5.1.18) from CD-1 mice was studied. A marked induction of hepatic GSH S-transferase from mice fed BHA was observed. Gel chromatography of liver cytosol ...

    journal_title:Pharmacology

    pub_type: 杂志文章

    doi:10.1159/000138600

    authors: Nishiya H,Haga T,Nozue N,Komatsu T,Baba M,Ueda Y,Ono Y,Kunii O

    更新日期:1989-01-01 00:00:00

  • beta-adrenergic reactivity in conscious DOCA-salt hypertensive rats.

    abstract::The endocrine (plasma renin activity, insulin and ADH) and hemodynamic responses (heart rate and mean arterial pressure) to isoprenaline infusion were examined in conscious deoxycorticosterone-salt hypertensive rats (DS) and compared with uninephrectomized-salt control rats (US). A dose-related rise in plasma renin ac...

    journal_title:Pharmacology

    pub_type: 杂志文章

    doi:10.1159/000138522

    authors: Vargas F,Haro JM,Garcia-Torres L,Soler A,Garcia del Rio C

    更新日期:1989-01-01 00:00:00

  • Effect of atorvastatin treatment on isoproterenol-induced myocardial infarction in rats.

    abstract::In the present study, chronic treatment of atorvastatin was evaluated on isoproterenol-induced myocardial infarction. Male Sprague-Dawley rats (200 +/- 25 g) were randomized into the following four groups: (1) control group, (2) isoproterenol-treated group, (3) atorvastatin-treated group, and (4) isoproterenol- and at...

    journal_title:Pharmacology

    pub_type: 杂志文章

    doi:10.1159/000092308

    authors: Trivedi CJ,Balaraman R,Majithiya JB,Bothara SB

    更新日期:2006-01-01 00:00:00

  • Characterization of a functional angiotensin II receptor in Xenopus laevis heart.

    abstract::High-affinity (104 +/- 18 pmol/l) and high-density (204 +/- 25 fmol/mg) angiotensin II (AII) binding sites have been identified in Xenopus laevis heart membranes. Competition binding of [125I]Sar1,Ile8 angiotensin (SIA) to these receptors by peptide analogs selective for the mammalian AII receptor subtypes AT1 and AT2...

    journal_title:Pharmacology

    pub_type: 杂志文章

    doi:10.1159/000139186

    authors: Aiyar N,Baker E,Pullen M,Nuthulaganti P,Bergsma DJ,Kumar C,Nambi P

    更新日期:1994-04-01 00:00:00

  • Pioglitazone inhibits advanced glycation end product-induced TNF-α and MMP-13 expression via the antagonism of NF-κB activation in chondrocytes.

    abstract:OBJECTIVE:Advanced glycation end products (AGEs) play a pivotal role in the initiation and progression of osteoarthritis (OA). Peroxisome proliferator-activated receptor-γ (PPARγ) has been shown to exhibit anti-inflammatory and anticatabolic properties and to be protective in animal models of OA. This study was aimed t...

    journal_title:Pharmacology

    pub_type: 杂志文章

    doi:10.1159/000369074

    authors: Chen C,Ma C,Zhang Y,Zeng Y,Li Y,Wang W

    更新日期:2014-01-01 00:00:00

  • The effect of fenfluramine on disposition and rate of antipyrine elimination.

    abstract::The effect of fenfluramine, administered orally in a daily dose of 1 mg/kg for 40 days, on the disposition and rate of elimination of antipyrine was studied in 15 obese patients. Although the plasma half-life of antipyrine was unchanged, the apparent volume of distribution (1/kg) fell by 11.6% (p less than 0.001) and ...

    journal_title:Pharmacology

    pub_type: 杂志文章

    doi:10.1159/000136880

    authors: O'Malley K,Stevenson IH,West M

    更新日期:1975-01-01 00:00:00

  • A randomised, two-period, cross-over, open-label study to evaluate the pharmacokinetic profiles of single doses of two different flurbiprofen 8.75-mg lozenges in healthy volunteers.

    abstract:AIMS:To compare the bioavailability of a new oromucosal formulation of flurbiprofen 8.75-mg lozenges, developed by Alfa Wassermann S.p.A. (test drug) to that of marketed flurbiprofen 8.75-mg lozenges (Benactiv Gola®, reference drug). METHODS:This was an open, randomised, two-period, crossover, pharmacokinetic (PK) stu...

    journal_title:Pharmacology

    pub_type: 杂志文章,随机对照试验

    doi:10.1159/000336767

    authors: Matzneller P,Burian A,Martin W,Annoni O,Lauro V,Tacchi R,Brunner M,Zeitlinger M

    更新日期:2012-01-01 00:00:00

  • Central and peripheral actions of alpha 2-adrenergic agonists on renal function in Long-Evans and Brattleboro rats.

    abstract::The effects of 3 alpha 2-adrenergic receptor agonists on renal function in vasopressin (AVP)-deficient Brattleboro (DI) rats were evaluated. The aim of this study was to determine the relative contribution of central versus peripheral alpha 2-adrenoceptors in mediating diuresis and natriuresis, as well as the role of ...

    journal_title:Pharmacology

    pub_type: 杂志文章

    doi:10.1159/000138604

    authors: Dawson R Jr,Wallace DR

    更新日期:1989-01-01 00:00:00

  • Actions of the opioid antagonist, nalmefene, and congeners on reperfusion cardiac arrhythmias and regional left coronary blood flow.

    abstract::Opioid antagonists have been shown to prevent the occurrence of lethal arrhythmias following coronary reperfusion. In this study, we have examined the effect of a new, long-lasting, potent opioid antagonist, nalmefene, and congeners in the prevention of reperfusion arrhythmias in dogs. Nalmefene given at a dose of 1 m...

    journal_title:Pharmacology

    pub_type: 杂志文章

    doi:10.1159/000138713

    authors: Caldwell RW,Nagarajan R,Chryssanthis A,Tuttle RR

    更新日期:1990-01-01 00:00:00

  • Cardiac gap junction channels are upregulated by metoprolol: an unexpected effect of beta-blockers.

    abstract:BACKGROUND/AIMS:Since beta-adrenoceptors have been shown to affect cardiac gap junction channels, we wanted to elucidate the possible effect of metoprolol on the gap junction protein connexin-43, using racemic RS-metoprolol or the isomer R-metoprolol (no beta-adrenoceptor blockade) or S-metoprolol (beta(1)-adrenoceptor...

    journal_title:Pharmacology

    pub_type: 杂志文章

    doi:10.1159/000276982

    authors: Salameh A,Blanke K,Dhein S,Janousek J

    更新日期:2010-01-01 00:00:00

  • Pharmacokinetics of two novel bicalutamide formulations in healthy male volunteers.

    abstract::The oral bioavailability of two investigational formulations of bicalutamide was compared with the current clinical formulation. The first formulation was amorphous R-/S-bicalutamide in solid dispersion with a polymeric matrix of hydroxypropyl methylcellulose phthalate (HP55S) (R-/S-bicalutamide/HP55S); the second was...

    journal_title:Pharmacology

    pub_type: 杂志文章,随机对照试验

    doi:10.1159/000094599

    authors: Cantarini M,Fuhr R,Morris T

    更新日期:2006-01-01 00:00:00

  • Cholinergic pathway of gastric acid secretion in the isolated whole stomach of the mouse.

    abstract::The isolated whole stomach of the mouse has been used to study the effect of atropine on gastic acid secretion stimulated by acetylcholine, bethanechol and histamine. Atropine inhibited acid secretory response to acetylcholine and bethanechol in a competitive manner. The following pA2 values for atropine were calculat...

    journal_title:Pharmacology

    pub_type: 杂志文章

    doi:10.1159/000137441

    authors: Szelenyi I,Vergin H

    更新日期:1980-01-01 00:00:00

  • Sennosides and aloin do not promote dimethylhydrazine-induced colorectal tumors in mice.

    abstract::In a model of dimethylhydrazine-induced colorectal tumors in male mice aloin- or sennoside-enriched diets (0.03%) did not promote incidence and growth of adenomas and carcinomas after 20 weeks. Furthermore, in anthranoid-fed mice no significant changes in serum electrolytes as well as parameters of hepato- and nephrot...

    journal_title:Pharmacology

    pub_type: 杂志文章

    doi:10.1159/000139859

    authors: Siegers CP,Siemers J,Baretton G

    更新日期:1993-10-01 00:00:00

  • Efficacy and safety of prolonged-release trazodone in major depressive disorder: a multicenter, randomized, double-blind, flexible-dose trial.

    abstract:OBJECTIVE:To investigate the efficacy, safety, and clinical benefit of prolonged-release trazodone (Trittico) in the treatment of major depressive disorder (MDD). METHODS:In this study, 363 Chinese patients with MDD were randomized 1:1 to receive either prolonged-release trazodone (150-450 mg) or placebo treatment for...

    journal_title:Pharmacology

    pub_type: 杂志文章,多中心研究,随机对照试验

    doi:10.1159/000368559

    authors: Zhang L,Xie WW,Li LH,Zhang HG,Wang G,Chen DC,Cao Y,Cui LJ,Zhang KR,Shi JG,Tan QR,Zheng HB,Xu XF,Cheng ZH,Zhao JP

    更新日期:2014-01-01 00:00:00

  • Antiallodynic Effect of Intrathecal Korean Red Ginseng in Cisplatin-Induced Neuropathic Pain Rats.

    abstract:BACKGROUND:Chemotherapy-induced neuropathic pain (CINP) is a serious side effect of chemotherapy. Korean Red Ginseng (KRG) is a popular herbal medicine in Asian countries. We examined the therapeutic potential of intrathecally administered KRG for CINP and clarified the mechanisms of action with regard to 5-hydroxytryp...

    journal_title:Pharmacology

    pub_type: 杂志文章

    doi:10.1159/000503259

    authors: Kim YO,Song JA,Kim WM,Yoon MH

    更新日期:2020-01-01 00:00:00

  • A comparative study of zopiclone and flunitrazepam in insomniacs seen by general practitioners.

    abstract::A double-blind crossover trial was conducted in 42 outpatients of either sex in order to obtain information on the properties of 7.5 mg of zopiclone in a general practice setting compared with 2 mg of flunitrazepam. Each patient went through two periods of treatment, each period lasting 10 days. A comparison of the ef...

    journal_title:Pharmacology

    pub_type: 临床试验,杂志文章

    doi:10.1159/000137923

    authors: Wickstrøm E,Barbo SE,Dreyfus JF,Jerkø D,Kleiven R,Slåttbrekk R,Stray Tønnesen JN

    更新日期:1983-01-01 00:00:00

  • Superoxide anion stress attenuates the contractile response of the Guinea pig vas deferens to ATP and diadenosine tetraphosphate. Possible effect on calcium dysregulation.

    abstract::Induction of endogenous superoxide anion stress by the use of the superoxide dismutase inhibitor diethylthiocarbamate (DETCA; 10 mmol/l) produced a potent inhibition of the ATP (0.3-10 mmol/l) and diadenosine tetraphosphate (AP(4)A) contractile activity in the isolated vas deferens by 29-92 and 24-90%, respectively. P...

    journal_title:Pharmacology

    pub_type: 杂志文章

    doi:10.1159/000148260

    authors: Al-Rawi MB,Aleisa AM,Khattab MM

    更新日期:2008-01-01 00:00:00

  • Anticonvulsant effect of morphine and morphine-like analgesics in Mongolian gerbils.

    abstract::The effect of morphine, fentanyl, pethidine and pentazocine was studied in gerbils against air blast-induced seizures. Major, generalized seizures were suppressed by morphine (ED50 = 4.0 mg/kg s.c.), fentanyl (ED50 = 64 micrograms/kg s.c.), and pethidine (ED50 = 2.4 mg/kg s.c.), but not by pentazocine. The anticonvuls...

    journal_title:Pharmacology

    pub_type: 杂志文章

    doi:10.1159/000138189

    authors: Frey HH

    更新日期:1986-01-01 00:00:00