Abstract:
:Reducing the maximum plasma concentration whilst maintaining the exposure was shown to ameliorate adverse events following the oral administration of 6-hydroxybuspirone. This observation, along with a desire to provide for once daily dosing of this compound, provided the basis for the development of an extended release formulation. Hydrophilic matrix tablets based on hydroxypropyl methylcellulose and containing citric acid to provide for an acid microenvironment were prepared and evaluated by in vitro drug release studies and in vivo pharmacokinetic and scintigraphic studies using samarium oxide (¹⁵³Sm) labelled dosage forms. The dosage forms were found to release the contained drug by a predominantly diffusion mechanism and the release rate was relatively independent of environmental pH. Following administration of the extended release formulations to volunteers, comparative pharmacokinetic data indicated that the extended release formulations provided for a reduction in the maximum plasma concentration of 64-70% relative to that provided by the same dose given as an oral solution, whilst maintaining exposure relative to the oral solution. By examination of absorption curves derived by Wagner-Nelson analysis of pharmacokinetic data it was noted that drug release in vivo correlated well with drug release observed in vitro and no marked change in rate of absorption was noted when dosage forms were located in and releasing drug in the colon. The robust control of drug release seen in vitro translated to a good in vivo performance.
journal_name
Biopharm Drug Disposjournal_title
Biopharmaceutics & drug dispositionauthors
Nicholson SJ,Timmins P,Dockens RC,Connor A,Croop R,Ferrie P,Zeng J,Dennis AB,Wilding Idoi
10.1002/bdd.1819subject
Has Abstractpub_date
2012-12-01 00:00:00pages
522-35issue
9eissn
0142-2782issn
1099-081Xjournal_volume
33pub_type
杂志文章,随机对照试验abstract::The effects of age on hepatic microsomal enzyme induction were studied in male CD-1 mice. Six week old and 1 year old animals were treated with either phenobarbital (80 mg kg-1) or saline once daily for 3d. Twenty-four hours after the last treatment, animals were sacrificed and livers were harvested. Hepatic microsoma...
journal_title:Biopharmaceutics & drug disposition
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doi:10.1002/(sici)1099-081x(199703)18:2<139::aid-bdd7>
更新日期:1997-03-01 00:00:00
abstract::The pharmacokinetics and pharmacodynamics of furosemide were compared after an oral administration or a direct administration of Lasix into the duodenum in humans (40 mg). Furosemide was absorbed quickly after a direct administration of Lasix into the duodenum; the peak plasma concentration of furosemide was reached w...
journal_title:Biopharmaceutics & drug disposition
pub_type: 临床试验,杂志文章
doi:10.1002/(sici)1099-081x(199712)18:9<753::aid-bdd63
更新日期:1997-12-01 00:00:00
abstract::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 exte...
journal_title:Biopharmaceutics & drug disposition
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doi:10.1002/bdd.2201
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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
doi:10.1002/bdd.2510080304
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abstract::Betahistine, a potent histamine H3 receptor antagonist, is being developed for the treatment of attention deficit hyperactivity disorder (ADHD) that manifests with symptoms such as hyperactivity, impulsivity and inattention. This study describes the pharmacokinetics of betahistine in ADHD subjects at doses higher than...
journal_title:Biopharmaceutics & drug disposition
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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
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abstract::The present study was conducted in order to examine the intranasal administration of verapamil and compare this route to oral and intravenous administration in a 3 way crossover protocol in five dogs. Unanesthetized, adult mongrel dogs were given verapamil intravenously (0.5 mg/kg), orally (2.5 mg/kg) and intranasally...
journal_title:Biopharmaceutics & drug disposition
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doi:10.1002/bdd.2510060411
更新日期:1985-10-01 00:00:00
abstract::SYL-927, a novel and selective S1P1 agonist, is transferred to its active phosphate for the regulation of lymphocyte recirculation. This in vitro metabolism study is to elucidate the P450-mediated oxidation pathway of SYL-927 in human liver microsomes (HLMs). The results demonstrated that the ω-1 hydroxylated metaboli...
journal_title:Biopharmaceutics & drug disposition
pub_type: 杂志文章
doi:10.1002/bdd.2161
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abstract::In this comparative bioavailability study two sustained release capsule formulations of propranolol, one a clinical trial formulation and the other the U.K. sales formulation ('Inderal' LA), were compared with a conventional 'Inderal' tablet. Twelve healthy adult male volunteers received, on cross-over basis, on three...
journal_title:Biopharmaceutics & drug disposition
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1002/bdd.2510020105
更新日期:1981-01-01 00:00:00
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
doi:10.1002/(sici)1099-081x(199910)20:7<327::aid-bdd19
更新日期:1999-10-01 00:00:00
abstract::The bioavailability of orally administered therapies are often significantly limited in the human intestine by the metabolic activities of cytochrome P450 3A4 (CYP3A4) and P-glycoprotein (P-gp). Predicting whether candidate compounds induce CYP3A4 and P-gp is a crucial stage in the drug development process, as drug-dr...
journal_title:Biopharmaceutics & drug disposition
pub_type: 杂志文章
doi:10.1002/bdd.1927
更新日期:2015-04-01 00:00:00
abstract::The following results were obtained recently from our laboratories; in rats with 72-h water deprivation (rats with dehydration), the hepatic cytochrome P450 2E1 (CYP2E1) was three-fold induced with an increase in the mRNA. Rehydration of 48-h water-deprived rats for the next 24 h with free access of food (rats with re...
journal_title:Biopharmaceutics & drug disposition
pub_type: 杂志文章
doi:10.1002/bdd.335
更新日期:2003-03-01 00:00:00
abstract::Antiretroviral therapy has been the mainstay of treatment for neonates born to HIV infected mothers. Neonates born prematurely to HIV positive mothers are underdeveloped not only in anatomical terms but also in their physiological systems. Zidovudine, the first antiretroviral drug in clinical therapy for the treatment...
journal_title:Biopharmaceutics & drug disposition
pub_type: 杂志文章
doi:10.1002/bdd.2208
更新日期:2019-11-01 00:00:00
abstract::The lipophilic weak base amodiaquine is an antimalarial drug that has been in use for over 40 years. Little is known of amodiaquine's mechanism of transport across membranes. Transport experiments of amodiaquine in Caco-2 cells showed a low recovery of 30% and rapid disappearance from the apical chamber. Compounds str...
journal_title:Biopharmaceutics & drug disposition
pub_type: 杂志文章
doi:10.1002/bdd.616
更新日期:2008-09-01 00:00:00
abstract::A novel 5-aminolevulinic acid (ALA)-containing microparticulate system was produced recently, based on incorporation of ALA into particles prepared from a suppository base that maintains drug stability during storage and melts at skin temperature to release its drug payload. The novel particulate system was applied to...
journal_title:Biopharmaceutics & drug disposition
pub_type: 杂志文章
doi:10.1002/bdd.645
更新日期:2009-03-01 00:00:00
abstract::Few studies describe the administration of Taxol to rats; however, rats are typically used to study the toxicity of new drugs or novel formulations. A dose finding study was conducted to determine a safe dose of Taxol following intravenous administration in rats. Male Sprague-Dawley rats received a bolus of paclitaxel...
journal_title:Biopharmaceutics & drug disposition
pub_type: 杂志文章
doi:10.1002/bdd.503
更新日期:2006-05-01 00:00:00
abstract::After in vitro incubation of cecal content from CVL or gnotobiotic rats with rhein anthraquinone (1 mg g-1) for 18 h at 37 degrees, the anthraquinone was converted to rhein anthrone for 23.5 (SD +/- 3.4) per cent and 19.4 (+/- 4.7) per cent, respectively. Liquid cultures of some strictly anaerobic fecal bacteria of ma...
journal_title:Biopharmaceutics & drug disposition
pub_type: 杂志文章
doi:10.1002/bdd.2510130403
更新日期:1992-05-01 00:00:00
abstract::The pharmacokinetics of mexiletine and its metabolite hydroxy-methyl-mexiletine have been investigated following single-dose and during multiple-dose administration of a sustained-release form of mexiletine to six post-myocardial infarct patients. Comparison of single-dose and washout pharmacokinetics, after short-ter...
journal_title:Biopharmaceutics & drug disposition
pub_type: 杂志文章
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更新日期:1992-10-01 00:00:00
abstract::In situ intestinal absorption of baclofen in the rat in the presence of beta-alanine has been investigated. Through the perfusion of 0.50 mM baclofen solutions containing variable concentrations of the aminoacid (from 5 to 100 mM), a partially competitive inhibition of baclofen absorption was characterized: absorption...
journal_title:Biopharmaceutics & drug disposition
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更新日期:1991-12-01 00:00:00
abstract:PURPOSE:Amifostine is a prodrug in which selectivity is largely determined by the preferential formation and uptake of its cytoprotective metabolite, WR-1065, in normal tissues as a result of differences in membrane-bound alkaline phosphatase activity. It was hypothesized that amifostine may be a good candidate for reg...
journal_title:Biopharmaceutics & drug disposition
pub_type: 杂志文章
doi:10.1002/bdd.380
更新日期:2004-01-01 00:00:00
abstract::Previously we demonstrated that a hydrophilic HMG-CoA reductase inhibitor, pravastatin, was actively taken up by the liver via the 'multispecific anion transporter' using isolated rat hepatocytes (M. Yamazaki, H. Suzuki, M. Hanano, T. Tokui, T. Komai, and Y. Sugiyama, Am. J. Physiol., 264, G36-G44 (1993)). Such a carr...
journal_title:Biopharmaceutics & drug disposition
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doi:10.1002/(SICI)1099-081X(199612)17:9<775::AID-BDD99
更新日期:1996-12-01 00:00:00
abstract::Dolasetron, Anzemet, a 5-hydroxytryptamine receptor antagonist, is under investigation as an antiemetic agent. The keto-reduced metabolite of dolasetron has been identified in human plasma and is probably responsible for the majority of the antiemetic activity. This study evaluated the pharmacokinetics of dolasetron a...
journal_title:Biopharmaceutics & drug disposition
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1002/bdd.2510160303
更新日期:1995-04-01 00:00:00
abstract::Pharmacokinetics of ragaglitazar (a novel phenoxazine derivative of aryl propanoic acid), a potent insulin sensitizing and lipid-lowering compound was studied in Wistar rats. A single dose of 1, 3 or 10 mg/kg of ragaglitazar was given orally to male rats (n=4 per dose level) to evaluate dose proportionality. In anothe...
journal_title:Biopharmaceutics & drug disposition
pub_type: 杂志文章
doi:10.1002/bdd.413
更新日期:2004-10-01 00:00:00
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
doi:10.1002/bdd.2510130202
更新日期:1992-03-01 00:00:00
abstract::Radix Scutellariae (RS) and Coptis Chinensis (CC) are the most popular components in traditional Chinese medicine prescriptions. Flavonoids are the main effective ingredients in RS and berberine is the main effective ingredient in CC. The aim of this study was to determine the influence of CC on the pharmacokinetics o...
journal_title:Biopharmaceutics & drug disposition
pub_type: 杂志文章
doi:10.1002/bdd.674
更新日期:2009-10-01 00:00:00
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
doi:10.1002/bdd.2510160407
更新日期:1995-05-01 00:00:00
abstract::Gastrointestinal distress resulting from drug intake is often remedied by administering the drug with antacids. However, antacids have been shown to modify the absorption and excretion of many drugs. This study was designed to delineate the effects of aluminium and magnesium hydroxide antacid suspension (Maalox) on th...
journal_title:Biopharmaceutics & drug disposition
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1002/bdd.2510100610
更新日期:1989-11-01 00:00:00
abstract::Effects of concomitant colestipol administration on plasma concentrations of diltiazem and desacetyldiltiazem from immediate-release (IR) and sustained-release (SR) formulations were assessed in two studies. In the first study, 12 subjects received 120-mg diltiazem hydrochloride (diltiazem) SR capsules or 120-mg dilti...
journal_title:Biopharmaceutics & drug disposition
pub_type: 临床试验,杂志文章
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更新日期:2002-12-01 00:00:00
abstract::The bioequivalence of three oral forms of nifedipine was assessed in a triple crossover study on 12 healthy volunteers. Single 10 mg dose was given and ten blood samples were drawn during the first 8 h after administration. Highly sensitive gas chromatographic method was used for the nifedipine assay. Pharmacokinetic ...
journal_title:Biopharmaceutics & drug disposition
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1002/bdd.2510080104
更新日期:1987-01-01 00:00:00
abstract::The hypothesis that higher molecular weight (MW) quaternary ammoniums (QAs) form lipophilic ion-pair complexes with bile salts in the liver, and are subsequently excreted into bile via a canalicular transporter, P-gp, was re-examined in the present study for its validity. The biliary excretion of tributylmethyl ammoni...
journal_title:Biopharmaceutics & drug disposition
pub_type: 杂志文章
doi:10.1002/bdd.580
更新日期:2007-12-01 00:00:00