Metabolite profiling of guanfacine in plasma and urine of healthy Japanese subjects after oral administration of guanfacine extended-release tablets.


:Guanfacine is used for the treatment of attention-deficit/hyperactivity disorder (ADHD). Using liquid chromatography-tandem mass spectrometry (LC-MS/MS), metabolite profiling of guanfacine was performed in plasma and urine collected from healthy Japanese adults following repeated oral administration of guanfacine extended-release formulation. Unchanged guanfacine was the most abundant component in both plasma and urine (from the MS signal intensity). In plasma, the M3 metabolite (a sulfate of hydroxy-guanfacine) was the prominent metabolite; the M2 metabolite (a glucuronide of a metabolite formed by monooxidation of guanfacine), 3-hydroxyguanfacine and several types of glucuronide at different positions on guanfacine were also detected. In urine, the M2 metabolite and 3-hydroxyguanfacine were the principal metabolites. From metabolite analysis, the proposed main metabolic pathway of guanfacine is monooxidation on the dichlorobenzyl moiety, followed by glucuronidation or sulfation. A minor pathway is glucuronidation at different positions on guanfacine. As the prominent metabolites in plasma were glucuronide and sulfate of hydroxyguanfacine, which have no associated toxicity concerns, further toxicity studies of the metabolites, for example in animals, were not deemed necessary.


Biopharm Drug Dispos


Inoue Y,Morita H,Nozawa K,Kanazu T




Has Abstract


2019-09-01 00:00:00












  • TGF-β1 elevates P-gp and BCRP in hepatocellular carcinoma through HOTAIR/miR-145 axis.

    abstract::Multidrug resistance (MDR) is common in patients and has been linked to transforming growth factor-β1 (TGF-β1) and overexpression of drug efflux transporters P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP), although the molecular mechanisms remain largely unknown. This study aimed to investigate the ...

    journal_title:Biopharmaceutics & drug disposition

    pub_type: 杂志文章


    authors: Kong J,Qiu Y,Li Y,Zhang H,Wang W

    更新日期:2019-02-01 00:00:00

  • Pharmacokinetic analysis of absorption and metabolism of dopamine and a dopamine prodrug in dogs.

    abstract::Pharmacokinetic compartment models were constructed to describe the absorption and metabolism of dopamine (DA) and DA prodrug, N-(N-acetyl-L-methionyl)0,0-bis-eth-oxycarbonyl) dopamine(1). Plasma concentrations of DA, DA-SO4, and DOPAC after oral administration of DA to dogs, were analysed using the pharmacokinetic mo...

    journal_title:Biopharmaceutics & drug disposition

    pub_type: 杂志文章


    authors: Murata K,Noda K,Kohno K,Samejima M

    更新日期:1990-03-01 00:00:00

  • Effect of atorvastatin on the intravenous and oral pharmacokinetics of verapamil in rats.

    abstract::The present study aimed to investigate the effect of atorvastatin on the intravenous and oral pharmacokinetics of verapamil in rats. The pharmacokinetic parameters of verapamil were measured after an oral (9 mg/kg) or intravenous (3 mg/kg) administration of verapamil to rats in the presence and absence of atorvastatin...

    journal_title:Biopharmaceutics & drug disposition

    pub_type: 杂志文章


    authors: Choi DH,Chang KS,Hong SP,Choi JS,Han HK

    更新日期:2008-01-01 00:00:00

  • Bioactivation of loxoprofen to a pharmacologically active metabolite and its disposition kinetics in human skin.

    abstract::Loxoprofen (LX) is a prodrug-type non-steroidal anti-inflammatory drug which is used not only as an oral drug but also as a transdermal formulation. As a pharmacologically active metabolite, the trans-alcohol form of LX (trans-OH form) is generated after oral administration to humans. The objectives of this study were...

    journal_title:Biopharmaceutics & drug disposition

    pub_type: 杂志文章


    authors: Sawamura R,Sakurai H,Wada N,Nishiya Y,Honda T,Kazui M,Kurihara A,Shinagawa A,Izumi T

    更新日期:2015-09-01 00:00:00

  • Biopharmaceutics classification and intestinal absorption of chikusetsusaponin IVa.

    abstract::The objective of this study was to investigate the absorption behavior of chikusetsusaponin IVa (CHS-IVa) in the rat intestine using single-pass intestinal perfusion (SPIP) and to classify CHS-IVa into the biopharmaceutics classification system (BCS). The equilibrium solubility of CHS-IVa was determined by the shaker ...

    journal_title:Biopharmaceutics & drug disposition

    pub_type: 杂志文章


    authors: Zhang W,Liu H,Liu C

    更新日期:2019-09-01 00:00:00

  • Oxidative versus conjugative biotransformation of temazepam.

    abstract::Twenty-four healthy volunteers, aged 21-59 years, received single 30 mg oral doses of the benzodiazepine hypnotic temazepam. Levels of intact temazepam were determined in multiple plasma samples drawn during 48 h after dosage. Intact temazepam, its direct glucuronide conjugate, and the conjugate of its demethylated (o...

    journal_title:Biopharmaceutics & drug disposition

    pub_type: 杂志文章


    authors: Locniskar A,Greenblatt DJ

    更新日期:1990-08-01 00:00:00

  • Azimilide pharmacokinetics and pharmacodynamics upon multiple oral dosing.

    abstract::This study assessed steady-state azimilide pharmacokinetics and pharmacodynamics in 119 healthy male and female volunteers. Parallel groups of 18-40-year-old subjects received doses of 35, 100, 150 or 200 mg day(-1) for up to 14 days, with 1, 2 or 3 days of loading. Another group of > 55-year-old subjects received 100...

    journal_title:Biopharmaceutics & drug disposition

    pub_type: 临床试验,杂志文章,随机对照试验


    authors: Corey A,Al-Khalidi H,Brezovic C,Marcello S,Parekh N,Taylor K,Karam R

    更新日期:1999-03-01 00:00:00

  • Regional pharmacokinetics. II. Experimental methods.

    abstract::Regional pharmacokinetics is the study of the drug concentrations in specific regions of the body. It allows greater insight into the mechanisms of drug disposition than the study of systemic blood concentrations. Experimental methods in regional pharmacokinetics and their applications and limitations are reviewed. Po...

    journal_title:Biopharmaceutics & drug disposition

    pub_type: 杂志文章,评审


    authors: Upton RN,Runciman WB,Mather LE

    更新日期:1990-12-01 00:00:00

  • Metabolism of steroids by cytochrome P450 2C9 variants.

    abstract::CYP2C9 is a human microsomal cytochrome P450c (CYP). Much variation in CYP2C9 levels and activity can be attributed to polymorphisms of this gene. Wild-type CYP2C9 and ten mutants were co-expressed with NADPH-cytochrome P450 reductase in Escherichia coli. The hydroxylase activities toward steroids were examined. CYP2C...

    journal_title:Biopharmaceutics & drug disposition

    pub_type: 杂志文章


    authors: Uno T,Nakano R,Kitagawa R,Okada M,Kanamaru K,Takenaka S,Uno Y,Imaishi H

    更新日期:2018-09-01 00:00:00

  • Effects of proton pump inhibitors and famotidine on elimination of plasma methotrexate: Evaluation of drug-drug interactions mediated by organic anion transporter 3.

    abstract::Methotrexate (MTX) is an antifolate agent used in the treatment of numerous types of cancer, and eliminated by active tubular secretion via organic anion transporter 3 (OAT3). Gastric antisecretory drugs, such as proton pump inhibitors (PPIs) and histamine H2 receptor antagonists, are widely used among patients with c...

    journal_title:Biopharmaceutics & drug disposition

    pub_type: 杂志文章


    authors: Narumi K,Sato Y,Kobayashi M,Furugen A,Kasashi K,Yamada T,Teshima T,Iseki K

    更新日期:2017-12-01 00:00:00

  • Pharmacokinetics and hepatic first-pass effect of (-)-carbovir in the anesthetized rat.

    abstract::Studies were designed to allow an in vivo estimation of the hepatic extraction ratio and to test the hypothesis that the pharmacokinetic parameters of (-)-CBV are significantly different during anesthesia. (-)-CBV was administered as an i.v. bolus followed by i.v. infusion into either the portal (n = 3) or the jugular...

    journal_title:Biopharmaceutics & drug disposition

    pub_type: 杂志文章


    authors: Soria I,Zimmerman CL

    更新日期:1995-05-01 00:00:00

  • Inhibition of rat hepatic mitochondrial aldehyde dehydrogenase isozymes by repeated cyanamide administration: pharmacokinetic-pharmacodynamic relationships.

    abstract::The inhibition of rat hepatic mitochondrial aldehyde dehydrogenase (ALDH) isozymes was studied in apparent steady-state conditions after repeated intra-peritoneal cyanamide administration. The low-Km mitochondrial ALDH isozyme was more susceptible to cyanamide-induced inhibition (DI50 = 0.104 mg kg-1) than the high-Km...

    journal_title:Biopharmaceutics & drug disposition

    pub_type: 杂志文章


    authors: Pruñonosa Piera J,Obach R,Sagristá ML,Bozal J

    更新日期:1993-07-01 00:00:00

  • Pharmacokinetics of MDL 26479, a novel benzodiazepine inverse agonist, in normal volunteers.

    abstract::MDL 26479 is a new drug undergoing clinical evaluation for the treatment of depression and for memory loss associated with Alzheimer's disease. As part of a dose tolerance trial, the single- (SD) and multiple-dose (MD) pharmacokinetics of MDL 26479 were evaluated in healthy male volunteers. SDs ranging from 2 to 465 m...

    journal_title:Biopharmaceutics & drug disposition

    pub_type: 临床试验,杂志文章,随机对照试验


    authors: Robbins DK,Hutcheson SJ,Miller TD,Green VI,Bhargava VO,Weir SJ

    更新日期:1997-05-01 00:00:00

  • Bioavailability of phenylbutazone from a new enteric-coated formulation with superior dissolution characteristics.

    abstract::The bioavailability of an improved formulation of enteric-coated phenylbutazone with faster dissolution, more consistent in vitro rate of drug release and improved stability was compared in 8 normal subjects at doses of 100 and 200 mg with commercially available Butacote. Phenylbutazone was more rapidly absorbed from ...

    journal_title:Biopharmaceutics & drug disposition

    pub_type: 临床试验,杂志文章,随机对照试验


    authors: John VA,Goldsborough S,Morrison PJ,Rogers HJ,Spector RG,Bradbrook ID

    更新日期:1982-01-01 00:00:00

  • Relative lung and systemic bioavailability of sodium cromoglycate inhaled products using urinary drug excretion post inhalation.

    abstract::The relative lung and systemic bioavailability of sodium cromoglycate following inhalation by different methods have been determined using a urinary excretion pharmacokinetic method. On three separate randomised study days, 7 days apart, subjects inhaled (i) 4x5 mg from an Intal metered dose inhaler (MDI), (ii) 4x5 mg...

    journal_title:Biopharmaceutics & drug disposition

    pub_type: 临床试验,杂志文章,随机对照试验


    authors: Aswania O,Chrystyn H

    更新日期:2002-05-01 00:00:00

  • A physiologically based pharmacokinetic (PBPK) approach to evaluate pharmacokinetics in patients with cancer.

    abstract::Potential differences in pharmacokinetics (PK) between healthy subjects and patients with cancer were investigated using a physiologically based pharmacokinetic approach integrating demographic and physiological data from patients with cancer. Demographic data such as age, sex and body weight, and clinical laboratory ...

    journal_title:Biopharmaceutics & drug disposition

    pub_type: 杂志文章


    authors: Cheeti S,Budha NR,Rajan S,Dresser MJ,Jin JY

    更新日期:2013-04-01 00:00:00

  • Interpretation and estimates of mean residence time with statistical moment theory.

    abstract::The definitions of mean residence time of drug molecules in the body (MRT) from the literature are reviewed. A formal definition of MRT, based on excretion of drug molecules and amount of drug, a parameter which is independent of constancy of both clearance and volume of distribution, is introduced and compared to oth...

    journal_title:Biopharmaceutics & drug disposition

    pub_type: 杂志文章


    authors: Kasuya Y,Hirayama H,Kubota N,Pang KS

    更新日期:1987-05-01 00:00:00

  • In vitro activation of the corticosteroid ciclesonide in animal nasal mucosal homogenates.

    abstract::Ciclesonide, a new corticosteroid for allergic rhinitis, is administered as an inactive parent compound that is converted by esterases to the pharmacologically active metabolite, desisobutyryl-ciclesonide (des-CIC). This study investigated the in vitro activation of ciclesonide in nasal mucosa of multiple animal speci...

    journal_title:Biopharmaceutics & drug disposition

    pub_type: 杂志文章


    authors: Sato H,Nave R,Nonaka T,Mochizuki T,Takahama S,Kondo S

    更新日期:2007-03-01 00:00:00

  • The pharmacokinetics of ethosuximide enantiomers in the rat.

    abstract::A chiral gas chromatographic assay previously developed for quantitative analysis of ethosuximide and its major metabolites in rat urine has been adapted for the analysis of the drug in plasma. Ethosuximide, both as a racemic mixture and as the individual enantiomers, was administered to conscious rats by the intraven...

    journal_title:Biopharmaceutics & drug disposition

    pub_type: 杂志文章


    authors: Mifsud J,Collier PS,Millership JS

    更新日期:2001-03-01 00:00:00

  • The relationship between pharmacokinetic behaviour of glycyrrhizin and hepatic function in patients with acute hepatitis and liver cirrhosis.

    abstract::The pharmacokinetic behavior of glycyrrhizin in four patients with acute hepatitis (hepatitis group) and six patients with liver cirrhosis (cirrhosis group) receiving chronically an IV administration of a 120 mg dose once a day or once every other day of glycyrrhizin was investigated. The plasma concentration of glycy...

    journal_title:Biopharmaceutics & drug disposition

    pub_type: 临床试验,杂志文章


    authors: Yamamura Y,Tanaka N,Santa T,Kotaki H,Aikawa T,Uchino K,Osuga T,Sawada Y,Iga T

    更新日期:1995-01-01 00:00:00

  • Renal and non-renal clearances of iothalamate.

    abstract::An evaluation of the literature indicated that certain aspects of the disposition kinetics of iothalamate, important to the accurate determination of glomerular filtration rate in dogs and humans, remain to be resolved. The simultaneous clearances of iothalamate and inulin in 5 dogs were determined at three steady-sta...

    journal_title:Biopharmaceutics & drug disposition

    pub_type: 杂志文章


    authors: Prueksaritanont T,Lui CY,Lee MG,Chiou WL

    更新日期:1986-07-01 00:00:00

  • Bioavailability of propranolol and bendrofluazide formulations.

    abstract::In this comparative bioavailability study in 12 healthy volunteers the blood level profiles of both propranolol and bendrofluazide were studied following the multiple oral administration of the drugs as a fixed combination (Inderetic) and as a free combination at doses of 80 mg propranolol twice daily and 2.5 mg bendr...

    journal_title:Biopharmaceutics & drug disposition

    pub_type: 临床试验,杂志文章,随机对照试验


    authors: McAinsh J,Holmes BF,Baber NS,Young J

    更新日期:1981-04-01 00:00:00

  • Regional gastrointestinal delivery of remogliflozin etabonate in humans.

    abstract::Remogliflozin etabonate (RE) is the prodrug of remogliflozin (R), an inhibitor of renal glucose transport designed to reduce blood glucose concentrations for the treatment of type 2 diabetes. This open-label, randomized, single-dose, four-way crossover study, (with one add-on arm) in eight healthy men evaluated the re...

    journal_title:Biopharmaceutics & drug disposition

    pub_type: 杂志文章,随机对照试验


    authors: O'Connor-Semmes RL,Sandefer EP,Hussey EK,Tao W,Doll WJ,Page RC,Dobbins R

    更新日期:2013-03-01 00:00:00

  • Screening of non-steroidal anti-inflammatory drugs for inhibitory effects on the activities of six UDP-glucuronosyltransferases (UGT1A1, 1A3, 1A4, 1A6, 1A9 and 2B7) using LC-MS/MS.

    abstract::Non-steroidal anti-inflammatory drugs (NSAIDs) are used widely to relieve pain and to decrease inflammation. Several clinical studies have reported that NSAIDs inhibit uridine 5'-diphospho-glucuronosyltransferase (UGT) enzymes. Therefore, the study evaluated the inhibitory potential of 15 NSAIDs on the activities of s...

    journal_title:Biopharmaceutics & drug disposition

    pub_type: 杂志文章


    authors: Joo J,Kim YW,Wu Z,Shin JH,Lee B,Shon JC,Lee EY,Phuc NM,Liu KH

    更新日期:2015-05-01 00:00:00

  • Preclinical pharmacokinetics of a novel HIV-1 attachment inhibitor BMS-378806 and prediction of its human pharmacokinetics.

    abstract::BMS-378806 is a prototype of novel HIV attachment inhibitors that block the gp120 and CD4 interaction, the first step of HIV-1 entry into cells. The present work investigated the pharmacokinetics of BMS-378806 in rats, dogs and monkeys and assessed its in vitro permeability and metabolism. BMS-378806 exhibited species...

    journal_title:Biopharmaceutics & drug disposition

    pub_type: 杂志文章


    authors: Yang Z,Zadjura L,D'Arienzo C,Marino A,Santone K,Klunk L,Greene D,Lin PF,Colonno R,Wang T,Meanwell N,Hansel S

    更新日期:2005-12-01 00:00:00

  • The single dose pharmacokinetics and safety of deramciclane in healthy male volunteers.

    abstract::The pharmacokinetics and tolerability of a new putative non-benzodiazepine type anxiolytic compound deramciclane was studied in two consecutive studies. An open dose-escalation design was used to study doses from 0.2 to 50 mg in 18 healthy male volunteers. In the second study doses from 50 to 150 mg were investigated ...

    journal_title:Biopharmaceutics & drug disposition

    pub_type: 临床试验,杂志文章,随机对照试验


    authors: Kanerva H,Kilkku O,Heinonen E,Helminen A,Rouru J,Tarpila S,Scheinin M,Huupponen R,Klebovich I,Drabant S,Urtti A

    更新日期:1999-10-01 00:00:00

  • Bioequivalence of pyrantel pamoate dosage forms in healthy human subjects.

    abstract::Drugs that are largely restricted to the gastro-intestinal tract (GIT) for their therapeutic efficacy and that are not substantially absorbed into the body are usually inadequately studied in terms of systemic bioavailability. The possibility of systemic effects requires that bioavailabilities be studied to ensure aga...

    journal_title:Biopharmaceutics & drug disposition

    pub_type: 临床试验,杂志文章,随机对照试验


    authors: Fasanmade AA,Akanni AO,Olaniyi AA,Fasanmade AA,Tayo F

    更新日期:1994-08-01 00:00:00

  • The single-point method of dosage prediction: pharmacokinetic basis and method optimization.

    abstract::Based on the principle of superposition an expression has been established relating a drug concentration at steady-state to a concentration after a single dose. This relationship applies for drugs with linear pharmacokinetics given at equal dosage intervals and it is independent of the route of administration. The rel...

    journal_title:Biopharmaceutics & drug disposition

    pub_type: 杂志文章


    authors: Love BL,Tsuei SE,Thomas J,Nation RL

    更新日期:1982-07-01 00:00:00

  • Binding of tolmetin and salicylic acid to human serum albumin as a function of temperature.

    abstract::When drug-protein binding data are evaluated thermodynamically standard free energy (delta G0), standard enthalpy (delta H0) and standard entropy (delta S0) are usually estimated from association constants (Ka) derived from binding data obtained at only two temperatures. Estimation of delta H0 involves the assumption ...

    journal_title:Biopharmaceutics & drug disposition

    pub_type: 杂志文章


    authors: Behm HL,Flynn GL,Wagner JG

    更新日期:1981-07-01 00:00:00

  • Metabolism and disposition of EXP631--a novel antidepressant analgesic.

    abstract::EXP631, 4-(3-thienyl)-alpha, alpha,1-trimethyl-4-piperidine-methanol hemi-fumarate salt (I), is a centrally acting non-opioid analgesic compound with monoamine uptake blocking properties. EXP631 has analgesic effects in several animal models. It is intended to be used for the treatment of moderate to moderately severe...

    journal_title:Biopharmaceutics & drug disposition

    pub_type: 杂志文章


    authors: Wong YN,Burcham DL,Huang SM,Quon CY

    更新日期:1993-08-01 00:00:00