Abstract:
:AZ'0908 is a novel microsomal prostaglandin E synthase-1 inhibitor intended for oral administration. Pharmacokinetic experiments in rats showed that bioavailability was much lower than anticipated and increased following pretreatment with the nonspecific cytochrome P450 (CYP) inhibitor 1-aminobenzotriazole, presumably by inhibition of intestinal metabolism. Stability experiments in rat liver and intestinal fractions revealed that the intrinsic clearance (Cl(int)) was much higher in intestinal than in liver microsomes. Caco2 experiments showed that AZ'0908 was a substrate for breast cancer resistance protein. Permeability was generally high and the efflux component was saturable predicting good absorption. The Cl(int) values in human intestinal microsome and S9 fractions were low. A correlation occurred between in vitro intestinal metabolism and in vivo intestinal loss in rats and dogs. Enzyme identification experiments showed that human CYP2J2 was involved in the oxidation of AZ'0908. In rats, the major metabolic enzyme was not identified. However, rat CYP2J2 analogs were not investigated. Intestinal metabolism appeared to be a major occurrence, explaining intestinal loss of AZ'0908 in the rats. In view of good overall permeability, low in vitro intestinal turnover, and relative low intestinal abundance of CYP2J2, we predict that intestinal metabolism of AZ'0908 in human does not exert a major issue.
journal_name
J Pharm Scijournal_title
Journal of pharmaceutical sciencesauthors
Bylund J,Bueters Tdoi
10.1002/jps.23443subject
Has Abstractpub_date
2013-03-01 00:00:00pages
1106-15issue
3eissn
0022-3549issn
1520-6017pii
S0022-3549(15)31187-4journal_volume
102pub_type
杂志文章abstract::The conditions of sorption of penicillins and cephalosporins on nonionic macroporous copolymers of styrenedivinylbenzene were evaluated. By increasing the methanol concentration in the eluent, the sorption decreased. Salts exerted little influence on sorption. However, pH exerted a remarkable effect on sorption, and t...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600700906
更新日期:1981-09-01 00:00:00
abstract::Mycophenolate mofetil (MPM), a new immunosuppressant, is the morpholinoethyl ester of mycophenolic acid (MPA). The distribution in blood and pharmacokinetics of MPA after administration of MPM were examined. The plasma to erythrocyte concentration ratio was low (0.10-0.15). MPA existed in rat plasma as the highly boun...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1021/js9502480
更新日期:1996-03-01 00:00:00
abstract::A theoretical analysis of a proposed drug delivery device is presented. The device is of cylindrical shape with an opening on its side surface. Analytical expressions for the temporal variations in the amount of drug released and the size of the unreleased portion of the device are derived. The result of numerical sim...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600810905
更新日期:1992-09-01 00:00:00
abstract::This work was to investigate the effects of particle size and paddle speed on the particle diffusional layer thickness h(app) in a USP dissolution apparatus II. After the determination of the powder dissolution rates of five size fractions of fenofibrate, including <20, 20-32, 32-45, 63-75, and 90-106 microm, the pres...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.21345
更新日期:2008-11-01 00:00:00
abstract::Optical coherence tomography (OCT) is a recently developed optical technique that produces depth profiles of three-dimensional objects. It is a nondestructive interferometric method responding to refractive index variation in the sample under study and can reach a penetration depth of a few millimetres. OCT employs ne...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.21844
更新日期:2010-01-01 00:00:00
abstract::The equilibrium kinetics of triazolam in aqueous solution was investigated in the pH range of 1-11 at body temperature. The quantitative study indicated that it forms equilibrium mixtures consisting of ring-opened and closed forms with the composition being dependent on pH. The equilibrium constants of the two species...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600711206
更新日期:1982-12-01 00:00:00
abstract::Blood levels of intact chloroprocaine were determined using a GLC procedure capable of detecting as little as 10 ng of chloroprocaine/ml of blood. It was necessary to detective plasma cholinesterases in collected samples by adding echothiophate iodide to blood sampling tubes. An extraction procedure, followed by a TLC...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600680123
更新日期:1979-01-01 00:00:00
abstract::Acitretin, a retinoid for the treatment of severe psoriasis, exhibits extremely low aqueous solubility and high photosensitivity. This study investigated the effects of the complexation of acitretin with the respective hydroxypropyl-beta-cyclodextrin (HPBCD) and randomly substituted methyl-beta-cyclodextrin (RMBCD) on...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.10495
更新日期:2003-12-01 00:00:00
abstract::Reactive high gravity controlled precipitation (HGCP) was carried out to produce salbutamol sulphate (SS) particles suitable for inhalation. Aqueous solutions of free salbutamol base and sulphuric acid were mixed intensely inside a HGCP reactor to form the particles. Spray drying was employed to obtain dry powders. Ph...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.21026
更新日期:2008-02-01 00:00:00
abstract::Drug-induced phototoxic skin responses involves photoirritation, photoallergy, and photogenotoxicity. In the present study, we attempted to develop effective analytical tools to predict the photogenotoxic potential of pharmaceutical substances on the basis of their photobiological and DNA-binding properties. Photoclea...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.21670
更新日期:2009-10-01 00:00:00
abstract::Respirable crystals of cromoglycic acid (CA) were prepared by precipitation of CA with hydrochloric acid from aqueous solutions of cromolyn sodium and subsequent recrystallization from hot water or mixtures of dimethyl sulphoxide and water. The properties of the materials were established by melting point measurements...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600780221
更新日期:1989-02-01 00:00:00
abstract::In this study, we attempted to improve the oral absorption of ceftriaxone (CTX) by using an absorption carrier and the CTX complex together. After the CTX-Ca-carrageenan gel complex was prepared, several kinds of compounds (Capmul MCM C10, Gelucire 44/14, glycyrrhizin) were screened as potential oral enhancers for our...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.10563
更新日期:2004-03-01 00:00:00
abstract::Hard gelatin capsule (HGC) shells are widely used to encapsulate drugs for oral delivery but are vulnerable to gelatin cross-linking, which can lead to slower and more variable in vitro dissolution rates. Adding proteolytic enzymes to the dissolution medium can attenuate these problems, but this complicates dissolutio...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1016/j.xphs.2018.08.009
更新日期:2018-12-01 00:00:00
abstract::The physical state of a dosage form, crystalline versus amorphous, is critical in determining its solid-state physical and chemical properties. This minireview describes the physics associated with the preparation and storage of amorphous solids including a review of the common theories of the glass transition and rel...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章,评审
doi:10.1002/jps.10489
更新日期:2004-01-01 00:00:00
abstract::A method for the measurement of a potential diuretic-antihypertensive agent, (+/-)-[[6,7-dichloro-2-(4-fluorophenyl)-2-methyl-1-oxo-5-indanyl] oxy]acetic acid, in biological fluids is described. The procedure involves the addition of a related internal standard to the specimens followed by extraction of the acids into...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600730234
更新日期:1984-02-01 00:00:00
abstract::The spherically agglomerated crystals of aminophylline (theophylline-ethylenediamine complex) can be compounded directly into pharmaceutical formulations without further processing, e.g., granulation. Such crystals were prepared by mixing theophylline and ethylenediamine in a partially miscible solvent system, i.e., o...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600731021
更新日期:1984-10-01 00:00:00
abstract::The inclusion complexation of homologous derivatives of steroid hormones with cyclodextrins and 2-hydroxypropyl-beta-cyclodextrin (2-HP-beta-CD) was investigated with regard to underlying structure-interaction relationship. The interaction was studied by phase solubility analysis and stabilization effects of complex f...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600810808
更新日期:1992-08-01 00:00:00
abstract::A potentiometric study of lithium complexation with tyramine, dopamine, norepinephrine, and 5-hydroxytryptamine was undertaken using monovalent cationic selective and pH glass electrodes. The conditional stability constants for the lithium catecholamine complexes were calculated for a range of pH values from direct po...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600750117
更新日期:1986-01-01 00:00:00
abstract::A high-performance liquid chromatographic method with spectrofluorometric detection has been developed for the analysis of a new substituted benzamide and its metabolite in body fluids. The detection was performed at 270 nm for excitation, and 370 nm for emission. The proposed technique is selective, reliable, and sen...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600790617
更新日期:1990-06-01 00:00:00
abstract::Crystallization of polymorphs still has a touch of art, as even prior observations of polymorphs do not guarantee their crystallization. However, once crystals of various polymorphs have been obtained, their relative stabilities can be established with a straightforward thermodynamic approach even if the conclusion wi...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.24626
更新日期:2015-12-01 00:00:00
abstract::Two human bioavailability studies were conducted to assess the in vivo performances of recently marketed 200-, 300-, and 400-mg ibuprofen capsules relative to the innovator's 300- and 400-mg tablets when administered as single oral 300- or 400-mg doses. An ibuprofen oral solution was also administered in each trial. W...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600710920
更新日期:1982-09-01 00:00:00
abstract::Biopolymer-based hydrogels such as mucus and the basal lamina play a key role in biology, where they control the exchange of material between different compartments. They also pose a barrier that needs to be overcome for successful drug delivery. Characterizing the permeability properties of such hydrogels is mandator...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.22737
更新日期:2012-01-01 00:00:00
abstract::A pharmacokinetic model was developed describing the pharmacokinetics of stannous fluoride in human subjects after oral topical application of a stannous fluoride dentifrice. Twenty subjects participated in an investigation of an experimental dentifrice. Subjects rinsed their mouths with the experimental dentifrice sl...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.21691
更新日期:2009-10-01 00:00:00
abstract::The purpose of the present study was to develop guidance toward rational choice of blenders and processing conditions to make robust and high performing adhesive mixtures for dry-powder inhalers and to develop quantitative experimental approaches for optimizing the process. Mixing behavior of carrier (LH100) and Astra...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1016/j.xphs.2016.07.012
更新日期:2017-01-01 00:00:00
abstract::The solubility equation of Yalkowsky was used to estimate the aqueous solubility of 33 barbiturates in the temperature range of 5 to 45 degrees C. The equation was extended by adding a term which accounts for the effect of pH on the solubility of the drug. The extended equation is successful in estimating the aqueous ...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600760120
更新日期:1987-01-01 00:00:00
abstract::The disposition of radioactivity following oral administration of 14C-norgestimate was compared to that following administration of the drug in combination with 3H-ethinyl estradiol in humans. Seven normal, healthy female subjects were each administered one capsule orally containing 14C-norgestimate either alone (74.4...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600671020
更新日期:1978-10-01 00:00:00
abstract::Pharmaceutical materials, crystalline and amorphous, sorb water from the atmosphere, which affects critical factors in the development of drugs, such as the selection of drug substance crystal form, compatibility with excipients, dosage form selection, packaging, and product shelf-life. It is common practice to quanti...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.23806
更新日期:2014-09-01 00:00:00
abstract::Chitosan and egg phosphatidylcholine (ePC) were used as a unique combination to prepare composite films for localized drug delivery. In comparison to other phospholipids analyzed, ePC was found to produce chitosan-based films with minimal swelling and a high degree of stability. The properties of the chitosan-ePC film...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.20379
更新日期:2005-07-01 00:00:00
abstract::Solubilities in isoctane and water were determined for several C1-phenolic esters of prostaglandin F2 alpha and prostaglandin E2 and acetates having the same phenol moiety. Linear free energy relationships for solubility among the series were observed with slopes of approximately 1. These results suggest that the cont...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600690417
更新日期:1980-04-01 00:00:00
abstract::The binding of nine diazepines to human serum albumin (HSA) and to alpha 1-acid glycoprotein (AGP) was investigated by means of fluorescence and circular dichroism (CD) spectroscopies. The binding parameters of diazepam obtained from fluorescence agreed with those obtained from CD measurements. Diazepines have one tig...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600810104
更新日期:1992-01-01 00:00:00