Enantioselective pharmacokinetics in animals of pazinaclone, a new isoindoline anxiolytic, and its active metabolite.


:The enantioselective pharmacokinetics of a new anxiolytic, pazinaclone (DN-2327), and its active metabolite, M-II, were studied in animals. In rats and dogs given racemic pazinaclone intravenously, the total clearance and volume of distribution of (S)-pazinaclone were lower than those of (R)-pazinaclone, whereas the opposite results were obtained in monkeys. The differences in disposition were consistent with enantioselective protein binding, where the unbound fraction was greater for (R)-pazinaclone than that for the (S)-enantiomer in rats and dogs; the reverse was noted in monkeys. Lower clearance and distribution for (S)-pazinaclone in rats and dogs, and for the (R)-enantiomer in monkeys, resulted in comparable plasma profiles for the pazinaclone enantiomers and thereby those of the corresponding enantiomers of M-II. The unbound clearance (CLu) of (S)-pazinaclone was, however, greater than that of the antipode in rats and dogs and the CLu of each enantiomer was similar in monkeys. Thus, enantioselectivity in the kinetics of (S)- and (R)-pazinaclone appears to reside largely in plasma binding differences and is unrelated to variations in intrinsic clearance. The first-pass metabolism of (S)- and (R)-pazinaclone on oral administration of the racemate was enantioselective, with respective bioavailabilities of 1.7 and 0.8% in rats, 10.4 and 1.9% in dogs, and 0 and 11.4% in monkeys. Therefore, the enantioselectivity was more pronounced after oral dosing.


Biopharm Drug Dispos


Kondo T,Yoshida K,Yoshimura Y,Tanayama S




Has Abstract


1995-12-01 00:00:00












  • Effects of aripiprazole and its active metabolite dehydroaripiprazole on the activities of drug efflux transporters expressed both in the intestine and at the blood-brain barrier.

    abstract::The inhibition potencies of aripiprazole and its active metabolite, dehydroaripiprazole, on the activities of human multidrug resistance protein 1 (MDR1/ABCB1; P-glycoprotein), breast cancer resistance protein (BCRP/ABCG2) and multidrug resistance-associated protein 4 (MRP4/ABCC4), that are drug efflux transporters ex...

    journal_title:Biopharmaceutics & drug disposition

    pub_type: 杂志文章


    authors: Nagasaka Y,Oda K,Iwatsubo T,Kawamura A,Usui T

    更新日期:2012-09-01 00:00:00

  • Pharmacokinetics of controlled-release verapamil in healthy volunteers and patients with hypertension or angina.

    abstract:AIMS:To study the dose-ranging population pharmacokinetics of controlled release verapamil in healthy subjects and patients with angina or hypertension. To characterize the pharmacodynamics of controlled-release verapamil in patients with hypertension. METHODS:Dose-ranging studies were conducted in healthy volunteers ...

    journal_title:Biopharmaceutics & drug disposition

    pub_type: 杂志文章


    authors: Gupta S,Modi NB,Sathyan G,Ho Pl PL,Aarons L

    更新日期:2002-01-01 00:00:00

  • The effect of food on the pharmacokinetics of the bicalutamide ('Casodex') enantiomers.

    abstract::'Casodex' (bicalutamide) is an orally active, non-steroidal, pure antiandrogen; it is a racemate with antiandrogenic activity residing predominantly in the (R)-enantiomer. Healthy male volunteers (n = 15) were administered single oral doses of bicalutamide (50 mg) after food and after fasting as part of a three-treatm...

    journal_title:Biopharmaceutics & drug disposition

    pub_type: 临床试验,杂志文章,随机对照试验


    authors: Cockshott ID,Oliver SD,Young JJ,Cooper KJ,DC Jones

    更新日期:1997-08-01 00:00:00

  • Bioequivalence of immediate-release theophylline capsules.

    abstract::A three-way crossover study in 18 healthy male volunteers was conducted to evaluate the bioequivalence of three different 200 mg anhydrous theophylline immediate-release (IR) capsules. The products had not been rated as therapeutically equivalent by the US Food and Drug Administration (FDA) owing to a lack of bioequiv...

    journal_title:Biopharmaceutics & drug disposition

    pub_type: 临床试验,杂志文章,随机对照试验


    authors: Meyer MC,Jarvi EJ,Straughn AB,Pelsor FR,Williams RL,Shah VP

    更新日期:1999-12-01 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

  • Pharmacokinetics and pharmacodynamics of furosemide after intravenous and oral administration to spontaneously hypertensive rats and DOCA-salt-induced hypertensive rats.

    abstract::The pharmacokinetics and pharmacodynamics of furosemide were investigated after intravenous (i.v.), 1 mg/100 g body weight, and oral administration, 2 mg per 100 g body weight, to spontaneously hypertensive rats (SHRs) and deoxycorticosterone acetate-salt-induced hypertensive rats (DOCA-salt rats). After i.v. administ...

    journal_title:Biopharmaceutics & drug disposition

    pub_type: 杂志文章


    authors: Jang SH,Lee MG,Kim ND

    更新日期:1994-04-01 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

  • Stability of cucurbitacin E in human plasma: chemical hydrolysis and role of plasma esterases.

    abstract::It was shown previously that the anticancerous cytotoxic oxygenated triterpenes, cucurbitacin E (Cuc E) and its deacetylated form, cucurbitacin I (Cuc I), interacted differently with human serum albumin. In this study, the biochemical stability of Cuc E was investigated in vitro by reverse-phase high performance liqui...

    journal_title:Biopharmaceutics & drug disposition

    pub_type: 杂志文章


    authors: Saade M,Magdalou J,Ouaini N,Greige-Gerges H

    更新日期:2009-10-01 00:00:00

  • Single dose pharmacokinetics of HEPP, a new anticonvulsant in normal healthy volunteers.

    abstract::The pharmacokinetics and the dose proportionality of a new anticonvulsant compound, HEPP (D,L-3-hydroxy-3-ethyl-3-phenylpropionamide) was studied in healthy male volunteers as part of the pharmacological evaluation for new drugs. Study was performed administering doses of 250, 375, 500 and 625 mg of HEPP to six male v...

    journal_title:Biopharmaceutics & drug disposition

    pub_type: 临床试验,杂志文章


    authors: González-Esquivel DF,Rubio-Donnadieu F,Carvajal-Sandoval G,Jung HC

    更新日期:1998-12-01 00:00:00

  • Uptake of verteporfin by articular tissues following systemic and intra-articular administration.

    abstract::Photodynamic therapy (PDT) using the photosensitizer BPD-Verteporfin (liposomal benzoporphyrin derivative-monoacid ring A) has been shown in previous studies to be effective in the amelioration of inflammatory arthritis in both the MRL-lpr mouse and the New Zealand White (NZW) rabbit models, and could potentially offe...

    journal_title:Biopharmaceutics & drug disposition

    pub_type: 杂志文章


    authors: Chowdhary RK,Ratkay LG,Canaan AJ,Waterfield JD,Richter AM,Levy JG

    更新日期:1998-09-01 00:00:00

  • The effect of food and time of administration on the absorption of diethylamine chromocarbe.

    abstract::In order to evaluate the influence of food and time of administration on the absorption of diethylamine chromocarbe, a bioavailability study was performed in 8 volunteers by using a new method of plasmatic drug evaluation. The results obtained indicate that lunch has little effect on diethylamine chromocarbe absorptio...

    journal_title:Biopharmaceutics & drug disposition

    pub_type: 临床试验,杂志文章,随机对照试验


    authors: Aiache JM,Faurie M,Sibaud Y,Kaftelip JP,Aiache S

    更新日期:1986-05-01 00:00:00

  • Pharmacokinetic interactions in mice between irinotecan and MBL-II-141, an ABCG2 inhibitor.

    abstract:PURPOSE:The chromone derivative MBL-II-141, specifically designed to inhibit ABCG2, was previously demonstrated to combine strong inhibition potency, low toxicity and good efficiency in reversing resistance to irinotecan in a xenografted mouse model. Here, the pharmacokinetic interactions in mice between irinotecan, it...

    journal_title:Biopharmaceutics & drug disposition

    pub_type: 杂志文章


    authors: Hénin E,Honorat M,Guitton J,Di Pietro A,Payen L,Tod M

    更新日期:2017-07-01 00:00:00

  • Theophylline controlled-release formulations: in vivo-in vitro correlations.

    abstract::Four experimental controlled-release oral solid dosage formulations were developed and the in vitro dissolution characteristics of theophylline from these formulations were studied in USP apparatus I. Pharmacokinetic evaluation of these formulations was carried out in eight beagle dogs under fasting conditions. Theoph...

    journal_title:Biopharmaceutics & drug disposition

    pub_type: 杂志文章


    authors: Yu Z,Schwartz JB,Sugita ET

    更新日期:1996-04-01 00:00:00

  • Prednisone and prednisolone interconversion in the rabbit utilizing unbound concentrations.

    abstract::Prednisolone (POH) and prednisone (PO) were both administered via seven different intravenous infusions (three POH and four PO) in each of six rabbits to obtain steady state. Bolus doses of POH and PO were also administered to four of the rabbits. Plasma samples of POH and PO were analyzed by normal phase HPLC. Unboun...

    journal_title:Biopharmaceutics & drug disposition

    pub_type: 杂志文章


    authors: Hammarlund-Udenaes M,Benet LZ

    更新日期:1991-08-01 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

  • Identification of rat faecal, urinary and biliary metabolites of thionorphine, a novel mixed agonist-antagonist analgesic, using liquid chromatography/electrospray ionization tandem mass spectrometry.

    abstract::The biotransformation of thionorphine (N-cyclopropylmethyl-7alpha-[(s)-1-hydroxy-1-methyl-3-(2thiophene)-propyl]-6,14-endo-ethano tetrahydrooripavine), a new analgesic, was in-vestigated in rats. The results of metabolite analysis by liquid chromatography/electrospray ionization tandem mass spectrometry with positive ...

    journal_title:Biopharmaceutics & drug disposition

    pub_type: 杂志文章


    authors: Wei SX,Zhang ZQ,Wang XY,Guo JF

    更新日期:2004-04-01 00:00:00

  • Contribution of serum lipoproteins as carriers of antitumour agent RS-1541 (palmitoyl rhizoxin) in mice.

    abstract::The tumour uptake as well as the anti-tumour activity of RS-1541 (palmitoyl rhizoxin), a potent antineoplastic agent, were investigated in mice bearing M5076 sarcoma. After intravenous administration, 14C-RS-1541 preferentially bound to the lipoproteins, to which 14C-rhizoxin did not bind. 14C-RS-1541 showed persistin...

    journal_title:Biopharmaceutics & drug disposition

    pub_type: 杂志文章


    authors: Tokui T,Kuroiwa C,Tokui Y,Sasagawa K,Kawai K,Kobayashi T,Ikeda T,Komai T

    更新日期:1994-03-01 00:00:00

  • Pharmacokinetics of riluzole: evidence for glucuronidation as a major metabolic pathway not associated with UGT1A1 genotype.

    abstract::Pharmacokinetic studies of riluzole show a large inter-individual variability of the drug's clearance and serum concentrations. Optimizing the individual dosage of riluzole may have the potential to improve the effect of riluzole treatment on survival of patients with amyotrophic lateral sclerosis (ALS). Limited data ...

    journal_title:Biopharmaceutics & drug disposition

    pub_type: 临床试验,杂志文章


    authors: van Kan HJ,van den Berg LH,Groeneveld GJ,van der Straaten RJ,van Vught PW,Lie-A-Huen L,Guchelaar HJ

    更新日期:2008-04-01 00:00:00

  • Concentration-dependent clearance of procainamide in normal subjects.

    abstract::Four normal volunteers each received two intravenous doses of PA. The mean low dose was 3.30 mg kg-1 (infused over 20 minutes) while the mean high dose was 12.5 mg kg-1 (infused over 60 minutes). Blood samples were collected for 12 hours and urine was collected for 48 hours after each dose. PA concentrations were dete...

    journal_title:Biopharmaceutics & drug disposition

    pub_type: 杂志文章


    authors: Coyle JD,Boudoulas H,Mackichan JJ,Lima JJ

    更新日期:1985-04-01 00:00:00

  • Effect of dehydration on the disposition kinetics of erythromycin in rabbits.

    abstract::The effect of water deprivation on the physiologic, biochemical, and disposition parameters of erythromycin was investigated in rabbits. The packed cell volume, plasma glucose, and total lipid concentration increased significantly in dehydration. The pharmacokinetic parameters of erythromycin after intravenous adminis...

    journal_title:Biopharmaceutics & drug disposition

    pub_type: 杂志文章


    authors: Ahmad M,Niazi SK,Ahmad T,Muzaffar NA,Nawaz M

    更新日期:1992-03-01 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

  • 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

  • Atazanavir increases the plasma concentrations of 1200 mg raltegravir dose.

    abstract::Raltegravir is a human immunodeficiency virus (HIV)-1 integrase strand transfer inhibitor currently marketed at a dose of 400 mg twice-daily (b.i.d.). Raltegravir 1200 mg once-daily (q.d.) (investigational q.d. formulation of 2 × 600 mg tablets; q.d. RAL) was found to be generally well tolerated and non-inferior to th...

    journal_title:Biopharmaceutics & drug disposition

    pub_type: 杂志文章,随机对照试验


    authors: Krishna R,East L,Larson P,Valiathan C,Deschamps K,Luk JA,Bethel-Brown C,Manthos H,Brejda J,Gartner M

    更新日期:2016-12-01 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

  • Characterization of ethiofos absorption in the rat small intestine.

    abstract::The absorption characteristics of ethiofos were studied using the rat in situ intestine circulating perfusion technique. Slow absorption kinetics were observed for ethiofos with varying rates of absorption and metabolism/degradation in situ as a function of buffer and absorption enhancers. In most cases less than 10 p...

    journal_title:Biopharmaceutics & drug disposition

    pub_type: 杂志文章


    authors: Geary RS,Swynnerton NF,Timmons SF,Mangold DJ

    更新日期:1991-05-01 00:00:00

  • Pharmacogenomics of cancer chemopreventive isothiocyanate compound sulforaphane in the intestinal polyps of ApcMin/+ mice.

    abstract::Sulforaphane (SFN) is an isothiocyanate that is present in widely consumed vegetables. Previous studies have shown that SFN is effective in preventing carcinogenesis induced by carcinogens in rodents. Recently it was found that SFN could also suppress the growth of intestinal polyps in the ApcMin/+ mouse. In the prese...

    journal_title:Biopharmaceutics & drug disposition

    pub_type: 杂志文章


    authors: Khor TO,Hu R,Shen G,Jeong WS,Hebbar V,Chen C,Xu C,Nair S,Reddy B,Chada K,Kong AN

    更新日期:2006-12-01 00:00:00

  • Release of 5-fluorouracil from intramuscular w/o/w multiple emulsions.

    abstract::Comparative in vivo studies of aqueous solution, multiple w/o/w, and w/o emulsions showed that formulating 5-fluorouracil in emulsion systems significantly sustained the release of the drug from intramuscular injection sites in the rat. Intramuscular injection of the drug in both w/o and w/o/w emulsion systems produce...

    journal_title:Biopharmaceutics & drug disposition

    pub_type: 杂志文章


    authors: Omotosho JA,Whateley TL,Florence AT

    更新日期:1989-05-01 00:00:00

  • Pharmacokinetics and allometric scaling of levormeloxifene, a selective oestrogen receptor modulator.

    abstract::The pharmacokinetics of a new selective oestrogen receptor modulator levormeloxifene was investigated in mice, rats, cynomolgus monkeys and humans by compartmental pharmacokinetics. Levormeloxifene was administered as an oral solution in all studies. Allometric scaling was used to predict human pharmacokinetic paramet...

    journal_title:Biopharmaceutics & drug disposition

    pub_type: 杂志文章


    authors: Østerberg O,Kiehr B,Erichsen L,Poulsen HE,Ingwersen SH

    更新日期:2003-04-01 00:00:00

  • Pharmacokinetics and protein binding of the selective neuronal nitric oxide synthase inhibitor 7-nitroindazole.

    abstract::Utilization of nitric oxide (NO) synthase (NOS) inhibitors to probe the role of NO in various central nervous system processes requires use of an inhibitor selective for neuronal NOS, and is facilitated by knowledge of the pharmacokinetics of the inhibitor. The present project was undertaken to elucidate the dispositi...

    journal_title:Biopharmaceutics & drug disposition

    pub_type: 杂志文章


    authors: Bush MA,Pollack GM

    更新日期:2000-09-01 00:00:00

  • Nonstationary disposition of valproic acid during prolonged intravenous infusion: contributions of unbound clearance and protein binding.

    abstract::Circadian variations in disposition have been observed for a variety of agents, including anticonvulsants. Valproic acid (VPA), an anticonvulsant used to control generalized and partial seizures, has exhibited diurnal oscillations in steady-state concentrations during long-term administration to humans and non-human p...

    journal_title:Biopharmaceutics & drug disposition

    pub_type: 杂志文章


    authors: Arens TL,Pollack GM

    更新日期:2001-09-01 00:00:00