Abstract:
:Ketoconazole (KTZ) has 2 chiral centers with the therapeutically active form being a racemic mixture of 2 cis-enantiomers, namely, (2R,4S)-(+)-KTZ and (2S,4R)-(-)-KTZ. The aims of the present study were to examine the effects of (+)-KTZ, (-)-KTZ, and (±)-KTZ on aryl hydrocarbon receptor activation and subsequently CYP1A1 induction in both human HepG2 and murine Hepa1c1c7 hepatoma cells, and to further test their inhibitory effect using recombinant human and mouse CYP1A1 enzymes. Our results demonstrated that (+)-KTZ induced human CYP1A1 more than (-)-KTZ, whereas on the other hand (-)-KTZ induced murine Cyp1a1 more than (+)-KTZ at the mRNA, and activity levels. Human CYP1A1 showed higher affinity to 7ER compared with murine Cyp1a1 (Km values 13.29 nM for human vs. 168.1 nM for murine). The intrinsic clearance values for human and murine CYP1A1 were 194.1 and 87.6 μL/pmol P450/min, respectively, whereas, Vmax values were 2.58 and 14.73 pmol/pmol P450/min, respectively. (+)-KTZ and (-)-KTZ directly inhibited CYP1A1 activity by noncompetitive mechanism. The affinity of (-)-KTZ to interact with human CYP1A1 and murine Cyp1a1 was significantly different from (+)-KTZ, as the Ki values for human CYP1A1 and murine Cyp1a1 were 199.4 and 413.7 nM, respectively, for (+)-KTZ, and 269.3 and 230.8 nM, respectively, for (-)-KTZ.
journal_name
J Pharm Scijournal_title
Journal of pharmaceutical sciencesauthors
Anwar-Mohamed A,El-Sherbeni AA,Hamdy DA,Korashy HM,Brocks DR,El-Kadi AOdoi
10.1016/j.xphs.2015.12.009subject
Has Abstractpub_date
2016-03-01 00:00:00pages
1318-26issue
3eissn
0022-3549issn
1520-6017pii
S0022-3549(15)00206-3journal_volume
105pub_type
杂志文章abstract::α-Lipoic acid (ALA) is a powerful antioxidant valuable for prevention and treatment of ophthalmic complications such as diabetic keratopathy and retinopathy. The aim of this work was to develop micelle-based formulations that can enhance the solubility, stability, and corneal permeability of ALA. Compared to a convent...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1016/j.xphs.2016.03.006
更新日期:2016-09-01 00:00:00
abstract::A continuous nonisothermal-isothermal method for stability prediction was developed. The approach yields all necessary parameters for prediction, including reaction order. The experimental procedure involves changing the temperature of the samples being studied until degradation is rapid enough to proceed at a conveni...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600640826
更新日期:1975-08-01 00:00:00
abstract::Since the discovery of liposomes or lipid vesicles derived from self-forming enclosed lipid bilayers upon hydration, liposome drug delivery systems have played a significant role in formulation of potent drugs to improve therapeutics. Currently, most of these liposome formulations are designed to reduce toxicity and t...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.1023
更新日期:2001-06-01 00:00:00
abstract::This study was designed to examine the effect of benzalkonium chloride/ethylenediaminetetraacetic acid (BAK/EDTA) on the ocular bioavailability (Focular) of ketorolac tromethamine after ocular instillation to normal and de-epithelialized corneas of rabbits both in vitro and in vivo. The in vitro Focular of the formula...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1021/js9504189
更新日期:1996-04-01 00:00:00
abstract::In vitro iontophoretic administration of drugs through a microporous polyolefin membrane with hydrophilic urethane polymerfilled pores was done for the ionized drugs dexamethasone sodium phosphate, hydrocortisone sodium phosphate, and prednisolone sodium succinate, and for a nonionizable drug cortisone acetate. Curren...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600780308
更新日期:1989-03-01 00:00:00
abstract::A sensitive, simple, and rapid method for the quantitation of ibuprofen in plasma, using 1-(p-fluorobenzoyl)-5-methoxy-2-methylindole acetic acid as the internal standard, was developed. The method is based on reversed-phase high-pressure liquid chromatography with a mobile phase containing acetonitrile--0.1 M acetic ...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600700829
更新日期:1981-08-01 00:00:00
abstract::The α-keto carboxylic acid, pyruvic acid (1) was found to be a very effective peroxide scavenger but is subject to an aldol-like self-condensation/polymerization reaction. The purpose of this study was to evaluate the hydrogen peroxide, H2O2, scavenging ability of 3-methyl-2-oxobutanoic acid (2), 4-methyl-2-oxopentano...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1016/j.xphs.2016.03.041
更新日期:2016-09-01 00:00:00
abstract::Clinical lots of recombinant human platelet-activating factor acetylhydrolase (rhPAF-AH) were prepared in a lyophilized formulation. After reconstitution with sterile water for injection to form an aqueous solution (10 mM sodium citrate, 7.5 w/v% sucrose, and 0.1 w/v% Pluronic-F68, pH 6.5), a few visible, slowly growi...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.20237
更新日期:2005-02-01 00:00:00
abstract::The relationship between the lone tryptophan residue at position 214 and drug binding sites (Sites I and II) in human serum albumin (HSA) was studied by fluorescence energy transfer. The distance between the lone tryptophan residue and ligands bound to HSA was estimated by Förster's equation, taking into consideration...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600760510
更新日期:1987-05-01 00:00:00
abstract::Antisense phosphorodiamidate Morpholino oligomers (PMO) are resistant to degradation by cellular hydrolases, DNases, RNases, and phosphodiesterases, but remain sensitive to prolonged exposure to low pH. The present studies evaluate the oral fractional bioavailability, stability, and efficacy of two distinct PMO sequen...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.10088
更新日期:2002-04-01 00:00:00
abstract::Under pandemic-caused emergency, evaluation of the potential of existing antiviral drugs for the treatment of COVID-19 is relevant. Triazavirin, an antiviral drug developed in Russia for per-oral administration, is involved in clinical trials against SARS-CoV-2 coronavirus. This virus has affinity to epithelial cells ...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1016/j.xphs.2020.11.016
更新日期:2020-11-26 00:00:00
abstract::In recent years, controlled release coatings, comprised of drug-polymer composites, have been integrated with medical devices, improving device functionality and performance. However, relationships between material properties, manufacturing environment, composite (micro)structure, and subsequent release kinetics are n...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.21416
更新日期:2009-01-01 00:00:00
abstract::Nitroglycerin is rapidly lost from solution when incubated with red blood cells or whole blood. The assumption that the loss is enzymatic in nature may not be true, since no major metabolite is detected during this incubation. Explanation on the basis of a chemical reaction is also difficult, since the products of the...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600720403
更新日期:1983-04-01 00:00:00
abstract::Thiamine hydrochloride (Vitamin B(1), THCl) can exist as a nonstoichiometric hydrate (NSH) and as a hemihydrate (HH). NSH can contain up to approximately 1 molar equivalent of water and be dehydrated to an isomorphic desolvate (ID) with minimal change in lattice structure. Crystallographic and spectroscopic techniques...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.21876
更新日期:2010-02-01 00:00:00
abstract::Experimental solubilities are reported for anthracene in binary solvent mixtures containing p-dioxane with n-hexane, cyclohexane, n-heptane, methylcyclohexane, n-octane, cyclooctane, and isooctane at 25 degrees C. Results of these measurements, used in conjunction with the nearly ideal binary solvent (NIBS) model, ena...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600760807
更新日期:1987-08-01 00:00:00
abstract::Evidence is provided for the existence of a second discrete chemical form of meropenem at clinically relevant concentrations prepared from the marketed formulation of the drug. Proton and carbon-13 NMR spectra in D2O, coupled with tandem mass spectroscopy (MS/MS) and cross polarization/magic angle spinning (CP-MAS) NM...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1021/js970370u
更新日期:1998-05-01 00:00:00
abstract::Aliphatic polyesters have great utility as temporary prosthetics and surgical aids, and in drug delivery systems. Knowledge of the mechanism and pathways of hydrolysis can form a basis for the design and selection of a controlled-release system. Because of the importance of hydrolysis to the properties of such a syste...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600800815
更新日期:1991-08-01 00:00:00
abstract::The permeability coefficient, Kp, of pure unbranched alkanoic acids (C2-C7) applied to isolated porcine skin, reached a maximum in the solubility parameter (delta 2) range of 9.7-10 cal1 /2/cm3/2. When these and other penetrants were delivered from a solvent vehicle, the following linear relationships could be demonst...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600730426
更新日期:1984-04-01 00:00:00
abstract::This study compares one of the previously studied formulations with commercial amoxicillin capsules. The results indicate that the percentage of the dose absorbed is similar in both formulations; nevertheless, the amoxicillin capsules present a higher absorption rate. The in vivo--in vitro correlations in terms of res...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600710823
更新日期:1982-08-01 00:00:00
abstract::Currently, conjunctivitis is treated by frequent high dose administration of sparfloxacin eye drop solution. However, the eye drops are inconvenient because of low bioavailability, short ocular drug residence time, and need of frequent instillation, which lead to patient noncompliance affecting the routine life style ...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1016/j.xphs.2020.02.008
更新日期:2020-06-01 00:00:00
abstract::Free radical polymerization converts aqueous solutions of methacrylated inulin into cross-linked hydrogels. The purpose of this work was to study the hydrogel formation and to characterize the fully cured hydrogels. The gelation process of aqueous solutions of methacrylated inulin was monitored as a function of time b...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1021/js9802796
更新日期:1999-02-01 00:00:00
abstract::This whitepaper highlights current challenges and opportunities associated with continuous synthesis, workup, and crystallization of active pharmaceutical ingredients (drug substances). We describe the technologies and requirements at each stage and emphasize the different considerations for developing continuous proc...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.24252
更新日期:2015-03-01 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::In this study, the cytotoxicity of doxorubicin (DOX) loaded stearic acid grafted chitosan oligosaccharide (CSO-SA) micelles and its core modified drug delivery systems were investigated in vitro. The in vitro drug release experiments using cellular culture medium, Roswell Park Memorial Institute 1640 (RPMI-1640) mediu...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.21464
更新日期:2009-02-01 00:00:00
abstract::Nephropathic cystinosis is a rare autosomal recessive disease characterised by raised lysosomal levels of cystine in the cells of all the organs. It is treated by the 6-h oral administration of the aminothiol, cysteamine, which has an offensive taste and smell. In an attempt to reduce this frequency and improve the tr...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.23246
更新日期:2012-10-01 00:00:00
abstract::We extend and modify the Noyes-Whitney equation and the Hixon-Crowell cube root law to include surface roughness effects on the dissolution rate of drugs. The problem is treated theoretically in terms of the fractal reaction dimension, DR, of the effective surface which undergoes dissolution. Effects of changes in DR ...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600810111
更新日期:1992-01-01 00:00:00
abstract::Pharmaceutical scientists are often asked to assess the impact of modifications to the illumination in the manufacturing and product packaging environment on product quality. To assess the impact of switching light sources, four model compounds were exposed to standard fluorescent light, LED, and "yellow light" and th...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1016/j.xphs.2020.07.020
更新日期:2020-11-01 00:00:00
abstract::The binding of Cu2+ and Ni2+ to bovine, dog, and human serum albumin has been studied by the 35Cl NMR probe technique. The number of primary copper sites were estimated to be 1.3 for human serum albumin, 3.1 for bovine serum albumin, and 6.6 for dog serum albumin. A similar number of primary nickel sites was determine...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600740116
更新日期:1985-01-01 00:00:00
abstract::Blends of polymers with complementary properties hold promise for addressing the diverse, demanding polymer performance requirements in amorphous solid dispersions (ASDs), but we lack comprehensive property understanding for blends of important ASD polymers. Herein, we prepare pairwise blends of commercially available...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.23991
更新日期:2014-09-01 00:00:00
abstract::The overall apparent first-order rate constants (Kab) of small intestinal absorption of sulfadiazine were determined in rats in situ at various pHs (4.01-7.42) of the recirculation fluids at 32 degrees. The purpose of the study was to verify our hypothesis that the rate-determining step for the absorption of sulfonami...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600830208
更新日期:1994-02-01 00:00:00