当前位置： SCI文献检索 > EUROPEAN JOURNAL OF DRUG METABOLISM AND PHARMACOKINETICS期刊下所有文献 > Metabolism of the new alpha-1A-adrenergic receptor antagonist, phthalimide-phenylpiperazine analog (RWJ-69442), in rat, dog and human hepatic S9 fractions, and in rats.

Metabolism of the new alpha-1A-adrenergic receptor antagonist, phthalimide-phenylpiperazine analog (RWJ-69442), in rat, dog and human hepatic S9 fractions, and in rats.

Abstract：

:The in vitro and in vivo metabolism of RWJ-69442, an alpha-1A-adrenergic receptor antagonist, was investigated after incubation with rat, dog, and human hepatic S9 fractions in the presence of NADPH-generating system, and a single oral/iv dose administration to rats (oral: 100 mg/kg; iv: 10 mg/kg). Unchanged RWJ-69442 (> or =30% of the sample in vitro; < or =47% of the sample in vivo) plus 14 metabolites were profiled, quantified and tentatively identified on the basis of API-MS and MS/MS data. The metabolic pathways for RWJ-69442 are proposed via the 4 steps: 1. phenyl/piperazinylhydroxylation, 2. N/O-dealkylation, 3. N-dephenylation, and 4. dehydration. Pathway 1 formed OH-phenyl-RWJ-69442 (M1, 4-32% in vitro & in vivo), and diOH-RWJ-69442 (M4, <1-4% in vitro & in vivo). Pathway 2 generated O-desisopropyl-RWJ-69442 (M2, <1-21% in vitro & in vivo), N-desmethyl-RWJ-69442 (M3, 2-3% in vitro & in vivo), N-desmethyl-M2 (M6, 1-8% in vitro & in vivo), and N-dealkylated RWJ-69442 (M9, < or =1-17% in vitro & in vivo), and in conjunction with pathway 1 produced 6 minor to major oxidized metabolites, OH-M2 (M5, 1-2% in vitro), OH-M3 (M11, 4-6% in vivo), OH-M9 (M10, <1-34% in vitro & in vivo), O-desisopropyl-M9 (M12, 3-21% in vivo), O-desisopropyl-M10 (M13,2-12% in vivo), and dehydro-M13 (M14, 25% in vivo). Pathways 3 and 4 formed 2 minor metabolites, N-desphenyl-RWJ-69442 (M7, <1-12% in vitro & in vivo) and dehydrated-RWJ-69442 (M8, <1-2% in vitro), respectively. RWJ-69442 is extensively metabolized in vitro in the rat and human (except dog), and in vivo in the rat.

journal_name

Eur J Drug Metab Pharmacokinet

journal_title

European journal of drug metabolism and pharmacokinetics

authors

Wu WN,McKown LA,Kuo GH

doi

10.1007/BF03226416

keywords:

subject

Has Abstract

pub_date

2005-01-01 00:00:00

pages

113-20

issue

1-2

eissn

0378-7966

issn

2107-0180

journal_volume

30

pub_type

杂志文章

相关文献

EUROPEAN JOURNAL OF DRUG METABOLISM AND PHARMACOKINETICS文献大全
  • In vivo metabolism of 2-[1'-phenyl-3'-(3-chlorophenyl)-2'-propenylyden]hydrazino-3-methyl-4(3H)-quinazolinone in rats.

    abstract：:The aim of this study was to investigate by HPLC the in vivo metabolism of 2-[1'-phenyl-3'-(3-chlorophenyl)-2'-propenylyden]hydrazino-3-methyl-4(3H)-quinazolinone as a substrate, and as a model compound in rats. The substrate was dissolved in DMSO/water (1:4) and administered intraperitoneally at a dose of 100 mg/kg i...

    journal_title：European journal of drug metabolism and pharmacokinetics

    pub_type： 杂志文章

    doi：10.1007/BF03190629

    authors： Kaymakçioğlu BK,Aktan Y,Süzen S,Gökhan N,Koyunoğlu S,Erol K,Yeşilada A,Rollas S

    更新日期：2005-10-01 00:00:00

  • Assessment of Drug-Drug Interaction Potential Between Atorvastatin and LCZ696, A Novel Angiotensin Receptor Neprilysin Inhibitor, in Healthy Chinese Male Subjects.

    abstract：BACKGROUND AND OBJECTIVE:LCZ696 (sacubitril/valsartan), a novel angiotensin receptor neprilysin inhibitor has been recently approved for the treatment of patients with heart failure (HF) and reduced ejection fraction. As several HF patients are likely to use statins as co-medications, the potential for a pharmacokineti...

    journal_title：European journal of drug metabolism and pharmacokinetics

    pub_type： 临床试验,杂志文章

    doi：10.1007/s13318-016-0349-y

    authors： Ayalasomayajula S,Pan W,Han Y,Yang F,Langenickel T,Pal P,Zhou W,Yuan Y,Rajman I,Sunkara G

    更新日期：2017-04-01 00:00:00

  • Effect of Tamarindus indica. L on the bioavailability of ibuprofen in healthy human volunteers.

    abstract：:The influence of Tamarindus indica L fruit extract incorporated in a traditional meal on the bioavailability of Ibuprofen tablets 400 mg dose when given concurrently was studied in 6 healthy human volunteers. There was a statistically significant increase in the plasma levels of Ibuprofen and its metabolites hydroxy-i...

    journal_title：European journal of drug metabolism and pharmacokinetics

    pub_type： 杂志文章

    doi：10.1007/BF03190483

    authors： Garba M,Yakasai IA,Bakare MT,Munir HY

    更新日期：2003-07-01 00:00:00

  • Age-related changes in mRNA levels of hepatic transporters, cytochrome P450 and UDP-glucuronosyltransferase in female rats.

    abstract：:Hepatic transporters and metabolic enzymes affect drug pharmacokinetics. Limited information exists on the alteration in mRNA levels of hepatic transporters and metabolic enzymes with aging. We examined the effects of aging on the mRNA levels of representative hepatic drug transporters and metabolic enzymes by analyzi...

    journal_title：European journal of drug metabolism and pharmacokinetics

    pub_type： 杂志文章

    doi：10.1007/s13318-014-0208-7

    authors： Kawase A,Ito A,Yamada A,Iwaki M

    更新日期：2015-06-01 00:00:00

  • Disposition of paclitaxel (Taxol) and its metabolites in patients with advanced breast cancer (ABC) when combined with trastuzumab (Hercpetin).

    abstract：:Monoclonal antibodies are capable of modulating drug metabolising enzymes resulting in unexpected plasma concentrations of a drug when given concomitantly. Therefore plasma concentration of paclitaxel (PTX) and its metabolites has been monitored in 10 patients with advanced breast cancer during treatment with PTX alon...

    journal_title：European journal of drug metabolism and pharmacokinetics

    pub_type： 杂志文章

    doi：10.1007/BF03190613

    authors： Furtlehner A,Schueller J,Jarisch I,Ostermann E,Czejka M

    更新日期：2005-07-01 00:00:00

  • The pharmacokinetics of conventional and bioenhanced tablet formulations of danirixin (GSK1325756) following oral administration in healthy, elderly, human volunteers.

    abstract：:Danirixin (GSK1325756) is a small, high-affinity, selective and reversible CXCR2 antagonist in development for treatment of chronic obstructive pulmonary disease. The objective of the study was to evaluate the relative bioavailability, including the inter-subject variability, of a conventional immediate-release (IR) f...

    journal_title：European journal of drug metabolism and pharmacokinetics

    pub_type： 杂志文章,随机对照试验

    doi：10.1007/s13318-014-0179-8

    authors： Miller BE,Smart K,Mistry S,Ambery CL,Bloomer JC,Connolly P,Sanderson D,Shreeves T,Smith R,Lazaar AL

    更新日期：2014-09-01 00:00:00

  • Statistical aspects of bioequivalence testing between two medicinal products.

    abstract：:A generic drug product (test product) is bioequivalent to an innovator product (reference product) when their bioavailabilities in the same molar dose are similar. Bioavailability is expressed by pharmacokinetic parameters such as the area under plasma concentration-time curve (AUC), the maximum plasma concentration (...

    journal_title：European journal of drug metabolism and pharmacokinetics

    pub_type： 杂志文章

    doi：10.1007/BF03226406

    authors： Zintzaras E

    更新日期：2005-01-01 00:00:00

  • Gender Differences in the Effect of Calcitriol on the Body Disposition and Excretion of Doxorubicin in Mice.

    abstract：BACKGROUND AND OBJECTIVE:The antitumor activity and toxicity of doxorubicin are potentiated and attenuated by calcitriol, respectively. Potentially, calcitriol can be combined with doxorubicin for clinical benefit in chemotherapy. To gain insight into the interaction between doxorubicin and calcitriol, proposed for com...

    journal_title：European journal of drug metabolism and pharmacokinetics

    pub_type： 杂志文章

    doi：10.1007/s13318-020-00632-6

    authors： Durna Corum D,Uney K

    更新日期：2020-10-01 00:00:00

  • Study of the disposition kinetics of the N-oxide-derivative: a metabolite of picobenzide.

    abstract：:The disposition kinetics of the N-oxide of picobenzide were studied after administration to rabbits at a bolus dose of 30 mg/kg of picobenzide intravenously. The biotransformation process fits a first-order kinetic process, and the metabolite shows good access capacity to the peripheral compartment. The N-oxide of pic...

    journal_title：European journal of drug metabolism and pharmacokinetics

    pub_type： 杂志文章

    doi：10.1007/BF03190837

    authors： Santos Buelga D,Mariño EL,Domínguez-Gil A

    更新日期：1989-01-01 00:00:00

  • The metabolism and excretion of 7-mono-0-(beta-hydroxyethyl) rutoside in the dog.

    abstract：:Following i.v. administration of mono-HR to the beagle, plasma levels of both mono-HR and its glucuronide conjugates fell rapidly, neither being detectable 8 h after injection. Following oral administration of 14C-mono-HR, mono-HR-glucuronide was detected in plasma, confirming the absorption of mono-HR, and low levels...

    journal_title：European journal of drug metabolism and pharmacokinetics

    pub_type： 杂志文章

    doi：10.1007/BF03189428

    authors： Hackett AM,Griffiths LA

    更新日期：1979-01-01 00:00:00

  • Solid-phase extraction of piribedil and its metabolites from plasma and urine without and after deconjugation, by high performance liquid chromatography.

    abstract：:A new high performance liquid chromatographic procedure has been developed for the simultaneous quantification of piribedil (PD) and its three main basic metabolites in rat plasma and urine, without and after hydrolysis. The procedure relies on isolation of the compounds from plasma and urine constituents using the Se...

    journal_title：European journal of drug metabolism and pharmacokinetics

    pub_type： 杂志文章

    doi：10.1007/BF03190147

    authors： Sarati S,Caccia S

    更新日期：1992-07-01 00:00:00

  • Liver Perfusion Modifies Gd-DTPA and Gd-BOPTA Hepatocyte Concentrations Through Transfer Clearances Across Sinusoidal Membranes.

    abstract：BACKGROUND AND OBJECTIVES:Gadobenate dimeglumine (Gd-BOPTA) is a commercialised hepatobiliary contrast agent used during liver magnetic resonance imaging (MRI) to detect liver diseases. It enters into human hepatocytes through organic anion transporting polypeptides (OATP1B1/B3) and crosses the canalicular transporter ...

    journal_title：European journal of drug metabolism and pharmacokinetics

    pub_type： 杂志文章

    doi：10.1007/s13318-016-0382-x

    authors： Daire JL,Leporq B,Vilgrain V,Van Beers BE,Schmidt S,Pastor CM

    更新日期：2017-08-01 00:00:00

  • Ranitidine treatment and cortisol metabolism in man.

    abstract：:Experimental evidence suggested that H2-receptor antagonists may inhibit not only hepatic but also adrenal cytochrome P-450 dependent monooxygenases. Therefore, the effects of ranitidine (150 mg b.i.d. over 14 days) on cortisol metabolism and antipyrine clearance have been investigated in nine healthy volunteers. Urin...

    journal_title：European journal of drug metabolism and pharmacokinetics

    pub_type： 杂志文章

    doi：10.1007/BF03189981

    authors： Mönig H,Hoffmann K,Ohnhaus EE,Schulte HM

    更新日期：1992-01-01 00:00:00

  • Tolerability and Pharmacokinetics of Hydronidone, an Antifibrotic Agent for Hepatic Fibrosis, after Single and Multiple Doses in Healthy Subjects: an Open-Label, Randomized, Dose-Escalating, First-in-Human Study.

    abstract：BACKGROUND AND OBJECTIVES:Hydronidone is a novel pyridine derivative with therapeutic potential for hepatic fibrosis. The aim of this study was to investigate the safety, tolerability, and pharmacokinetics of hydronidone in healthy subjects. Effects of sex and food on hydronidone pharmacokinetics were also evaluated. ...

    journal_title：European journal of drug metabolism and pharmacokinetics

    pub_type： 杂志文章,随机对照试验

    doi：10.1007/s13318-015-0316-z

    authors： Liu Y,Wu J,Li Z,Luo Y,Zeng F,Shi S

    更新日期：2017-02-01 00:00:00

  • 4-Amino-3-(3'-methoxycarbonyl-2'-thioureido)benzophenone, a prodrug of mebendazole.

    abstract：:The compound 4-amino-3-(3'-methoxycarbonyl-2'-thioureido) benzophenone has shown promise as a prodrug of the anthelmintic mebendazole. The compound is stable in acid and neutral media and is rapidly hydrolysed in base. An HPLC assay procedure for mebendazole, the prodrug and their known or expected metabolites and deg...

    journal_title：European journal of drug metabolism and pharmacokinetics

    pub_type： 杂志文章

    doi：10.1007/BF03188765

    authors： Dawson M,Watson TR

    更新日期：1983-10-01 00:00:00

  • Quantitative studies on the occurrence of praziquantel in milk and plasma of lactating women.

    abstract：:10 healthy lactating women were treated orally with the anthelmintic praziquantel (Biltricide), and the resulting timedependent concentrations of the unchanged substance in plasma and milk were determined simultaneously. 5 of the women ("1st trial") received the single dose of 50 mg/kg; the other 5 women ("2nd trial")...

    journal_title：European journal of drug metabolism and pharmacokinetics

    pub_type： 杂志文章

    doi：10.1007/BF03189426

    authors： Pütter J,Held F

    更新日期：1979-01-01 00:00:00

  • Apomorphine pharmacokinetics in parkinsonism after intranasal and subcutaneous application.

    abstract：:Apomorphine was administered subcutaneously and intranasally to 7 patients suffering from Parkinsonism with 'on-off' problems. This comparative pharmacokinetic study showed that the two routes of administration are comparable with respect to absorption kinetics. Apomorphine is rapidly absorbed when administered intran...

    journal_title：European journal of drug metabolism and pharmacokinetics

    pub_type： 临床试验,杂志文章

    doi：10.1007/BF03192285

    authors： Sam E,Jeanjean AP,Maloteaux JM,Verbeke N

    更新日期：1995-01-01 00:00:00

  • Effect of plasma binding of ortho- and para-I-benzoates on their distribution in blood and into lymph, biotransformation and excretion in rat urine.

    abstract：:Two positional iodine derivatives of benzoic acid, i.e. ortho- (OIB) and para- (PIB), were used alone and in combination with salicylic acid (SA) to study the effects of plasma binding on their pharmacokinetics. Their lymphatic bioavailability (central lymph), their biotransformation and urinary excretion in rats were...

    journal_title：European journal of drug metabolism and pharmacokinetics

    pub_type： 杂志文章

    doi：10.1007/BF03188801

    authors： Lamka J,Láznícek M,Gallová S,Rudisar L,Kvĕtina J

    更新日期：1993-07-01 00:00:00

  • Plasma protein binding of penbutolol in pregnancy.

    abstract：:Penbutolol is a not cardioselective beta-adrenergic blocking drug; it is lipid soluble and differs in its protein binding from the other members of its group because shows linkage to alpha 1-glycoprotein, with no detectable binding to albumin. AAG levels change during pregnancy and so the binding of [3H]-penbutolol wa...

    journal_title：European journal of drug metabolism and pharmacokinetics

    pub_type： 杂志文章

    doi：10.1007/BF03189924

    authors： Aquirre C,Rodriguez-Sasiain JM,Navajas P,Calvo R

    更新日期：1988-01-01 00:00:00

  • Pharmacokinetic studies on IdB 1016, a silybin- phosphatidylcholine complex, in healthy human subjects.

    abstract：:IdB 1016 is a complex of silybin (the main active component of silymarin) and phosphatidylcholine, which in animal models shows greater oral bioavailability and therefore greater pharmacological activity compared with pure silybin and silymarin. In order to assess its pharmacokinetic profile in man, plasma silybin lev...

    journal_title：European journal of drug metabolism and pharmacokinetics

    pub_type： 临床试验,杂志文章,随机对照试验

    doi：10.1007/BF03190223

    authors： Barzaghi N,Crema F,Gatti G,Pifferi G,Perucca E

    更新日期：1990-10-01 00:00:00

  • Inhibition of diazepam metabolism in microsomal- and perfused liver preparations of the rat by desmethyldiazepam, N-methyloxazepam and oxazepam.

    abstract：:Hydroxylated metabolites of diazepam can be conjugated and are therefore generally thought not to affect the metabolism of diazepam. Liver microsomes, obtained from phenobarbital-pretreated rats, showed an inhibition of diazepam (10(-5) M) metabolism by desmethyldiazepam as well as by N-methyloxazepam or oxazepam (5 X...

    journal_title：European journal of drug metabolism and pharmacokinetics

    pub_type： 杂志文章

    doi：10.1007/BF03189692

    authors： Savenije-Chapel EM,Bast A,Noordhoek J

    更新日期：1985-01-01 00:00:00

  • Contribution of scintigraphy to verify the reliability of different preparation processes for enteric coated capsules.

    abstract：:The aim of this work was to use radiopharmaceuticals such as technetium (99mTc) and indium (DTPA-Ca111In) to visualize, with a gamma-camera, the disintegration area and time of 3 types of enteric coated hard gelatin capsules (obtained by 3 different preparation processes) and thus, to verify that they are really resis...

    journal_title：European journal of drug metabolism and pharmacokinetics

    pub_type： 临床试验,杂志文章

    doi：10.1007/BF03188829

    authors： Catteau D,Barthélémy C,Deveaux M,Robert H,Trublin F,Marchandise X,Van Drunen H

    更新日期：1994-04-01 00:00:00

  • Pharmacokinetics of a new oral formulation of amoxicillin.

    abstract：:The bioavailability of the recently developed 1 g dispersible tablet form of amoxicillin (B) and the 1 g dispersible tablet in suspension form (C) were compared to that of the 1 g standard reference formulation (A). Twelve healthy volunteers were involved in this single-dose, open, randomized, three-way cross-over stu...

    journal_title：European journal of drug metabolism and pharmacokinetics

    pub_type： 临床试验,杂志文章,随机对照试验

    doi：10.1007/BF03189784

    authors： Prevot MH,Jehl F,Rouveix B

    更新日期：1997-01-01 00:00:00

  • Evidence of reduced oral bioavailability of paracetamol in rats following multiple ingestion of grapefruit juice.

    abstract：:The aim of the current investigation was to assess the ability GFJ to modulate the pharmacokinetic profile of paracetamol following single or repeated administrations of GFJ in Sprague-Dawley rats. Diclofenac and carbamazepine were both used as positive controls. Rats received single GFJ or single distilled water dose...

    journal_title：European journal of drug metabolism and pharmacokinetics

    pub_type： 杂志文章

    doi：10.1007/s13318-014-0251-4

    authors： Qinna NA,Ismail OA,Alhussainy TM,Idkaidek NM,Arafat TA

    更新日期：2016-04-01 00:00:00

  • An attempt to establish an in vitro-in vivo correlation: case of paracetamol immediate-release tablets.

    abstract：:The purpose of this study was to investigate the possibility of developing different levels of in vitro-in vivo correlation for immediate-release paracetamol tablets using in vitro dissolution data obtained under various experimental conditions. The influence of agitation intensity and pH value of the dissolution medi...

    journal_title：European journal of drug metabolism and pharmacokinetics

    pub_type： 杂志文章

    doi：10.1007/BF03189824

    authors： Radovanović J,Durić Z,Jovanović M,Ibrić S,Petrović M

    更新日期：1998-01-01 00:00:00

  • Clinical Pharmacokinetics of a Lipid-Based Formulation of Risperidone, VAL401: Analysis of a Single Dose in an Open-Label Trial of Late-Stage Cancer Patients.

    abstract：BACKGROUND AND OBJECTIVES:A clinical trial was conducted to measure and analyse the pharmacokinetic parameters of a lipid formulation of risperidone, VAL401. The VAL401 formulation is designed to repurpose risperidone from an antipsychotic to an adenocarcinoma treatment, with the lipid formulation altering the cellular...

    journal_title：European journal of drug metabolism and pharmacokinetics

    pub_type： 杂志文章

    doi：10.1007/s13318-018-00538-4

    authors： Dilly SJ,Morris GS,Taylor PC,Parmentier F,Williams C,Afshar M

    更新日期：2019-08-01 00:00:00

  • Determination of the Pharmacokinetics and Tissue Distribution of Methyl 3,4-Dihydroxybenzoate (MDHB) in Mice Using Liquid Chromatography-Tandem Mass Spectrometry.

    abstract：BACKGROUND AND OBJECTIVES:Methyl 3,4-dihydroxybenzoate (MDHB) has the potential to prevent neurodegenerative diseases (NDDs). The present work aims to reveal the pharmacokinetics and tissue distribution characteristics of MDHB. METHODS:The pharmacokinetics and tissue distribution of MDHB were analyzed using LC-MS/MS a...

    journal_title：European journal of drug metabolism and pharmacokinetics

    pub_type： 杂志文章

    doi：10.1007/s13318-018-0512-8

    authors： Wang JH,Hu SH,Su JY,Pan JP,Mi XN,Geng HJ,Zhang W,Cai L,Su CF,Hong AH,Luo HM

    更新日期：2019-04-01 00:00:00

  • Influence of hepatic impairment on the pharmacokinetics of the dopamine agonist rotigotine.

    abstract：:The transdermally applied dopamine receptor agonist rotigotine is extensively metabolized in the liver. An open-label, parallel-group study was conducted to evaluate the effects of moderate hepatic impairment on the pharmacokinetics, safety and tolerability of rotigotine. Eight subjects with normal hepatic function an...

    journal_title：European journal of drug metabolism and pharmacokinetics

    pub_type： 杂志文章,多中心研究

    doi：10.1007/s13318-013-0153-x

    authors： Cawello W,Fichtner A,Boekens H,Braun M

    更新日期：2014-09-01 00:00:00

  • In vitro metabolism of galanthamine hydrobromide (Nivalin) by rat and rabbit liver homogenate.

    abstract：:The metabolism of galanthamine hydrobromide (Nivalin) was investigated in rat and rabbit liver homogenates. Experiments were carried out varying several parameters of incubation: substrate (galanthamine hydrobromide, galanthamine, galanthaminone and epigalanthamine), cofactor enrichment (NADPH, NADP/G-6-P, NAD), pH (7...

    journal_title：European journal of drug metabolism and pharmacokinetics

    pub_type： 杂志文章

    doi：10.1007/BF03189858

    authors： Mihailova D,Velkov M,Zhivkova Z

    更新日期：1987-01-01 00:00:00

  • Pharmacokinetic data processed by microcomputer for the formulation of optimal drug dosage form.

    abstract：:Microcomputers have been used in pharmacokinetics for several years, but their use in the area of formulation is a new application. By using appropriate data on the drug, the dosage form required and its mechanism of absorption and clearance, microcomputers can systematize and speed-up formulation, simplify manufactur...

    journal_title：European journal of drug metabolism and pharmacokinetics

    pub_type： 杂志文章,评审

    doi：10.1007/BF03189611

    authors： Aiache JM,Turlier M,Tanguy A

    更新日期：1984-04-01 00:00:00