Abstract：
:There has been a growing interest in predicting in vivo metabolic drug-drug interactions from in vitro systems. High-throughput screening methods aimed at assessing the potential of drug candidates for drug interactions are widely used in industry. However, at present, there is no consensus on methodologies that would yield reliable quantitative predictions, because a number of issues remain unsolved, such as estimations of inhibition constants in vitro and inhibitor concentration around the enzyme site in vivo. In the present review, different approaches to estimation of inhibitor concentration around the enzyme site are summarized; also, the problems associated with estimation of in vitro K(i) values due to incubation conditions and environment differences between in vitro and in vivo are presented. A new approach based on comparisons of in vitro and in vivo inhibition potencies by calculation of in vivo inhibition constants is discussed. Examples of predictions of in vivo drug interactions based on mechanism-based inactivation are described. Unresolved issues that would allow further refinement of existing prediction models are also evaluated.
journal_name
J Pharm Scijournal_title
Journal of pharmaceutical sciencesauthors
Yao C,Levy RHdoi
10.1002/jps.10179subject
Has Abstractpub_date
2002-09-01 00:00:00pages
1923-35issue
9eissn
0022-3549issn
1520-6017pii
S0022-3549(16)31070-Xjournal_volume
91pub_type
杂志文章,评审abstract：:The bioavailability of clofibric acid from formulations containing calcium clofibrate along and mixed with calcium carbonate (1:1 w/w) was compared to that from a standard clofibrate formulation in a crossover study in 12 human subjects. The 95% confidence intervals of bioavailability differences were such that they ...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600661138
更新日期：1977-11-01 00:00:00
abstract：:Anthralin and its decomposition products were separated by both column chromatographic and TLC techniques. Two decomposition products were characterized by TLC, melting-point data, and UV and IR spectroscopy. Pure anthralin and its decomposition products also were determined quantitatively. ...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600680340
更新日期：1979-03-01 00:00:00
abstract：:Previous studies have shown that protein storage stability in freeze-dried l-arginine-based systems improved in the presence of chloride ions. However, chloride ions reduced the glass transition temperature of the freeze concentrate (Tg') and made freeze drying more challenging. In this study, l-arginine was freeze dr...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1016/j.xphs.2016.07.001
更新日期：2016-10-01 00:00:00
abstract：:A three-way crossover bioavailability study was performed using nine adult male volunteers with three different commercial prednisone tablets. Plasma samples were assayed for prednisolone, the active metabolite of prednisone, by a radioimmunoassay method. Statistical analysis showed significant differences in the rate...
journal_title：Journal of pharmaceutical sciences
pub_type： 临床试验,杂志文章
doi：10.1002/jps.2600641035
更新日期：1975-10-01 00:00:00
abstract：:This work involves the study of the solid-phase and solution crystallization behavior of the N-methylephedrine enantiomers. A systematic investigation of the melt phase diagram of the enantiomeric N-methylephedrine system was performed considering polymorphism. Two monotropically related modifications of the enantiome...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1016/j.xphs.2016.08.005
更新日期：2016-11-01 00:00:00
abstract：:Development of high-throughput release and characterization assays is critical for the effective support of the rapidly growing biologics pipeline for biotherapeutics. Clipping of polypeptide chains is commonly monitored during process optimization, formulation development, and stability studies. A reduced capillary e...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.22710
更新日期：2011-12-01 00:00:00
abstract：:The dissolution characteristics of dicumarol were markedly enhanced by preparing dispersions of drug in polyethylene glycol 4000. Solid dispersions of varying weight fractions were formed by a melt method without measurable drug degradation or evaporation. There were no significant differences in dissolution rates amo...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600701217
更新日期：1981-12-01 00:00:00
abstract：:A study of the pH of saliva produced by humans sucking hard candy lozenges containing zinc gluconate and citric acid demonstrated the probability that the formulation delivered an insignificant amount of the contained zinc as Zn2+. This could account for the negative results of several clinical studies of this lozenge...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600810205
更新日期：1992-02-01 00:00:00
abstract：:Scale up of pan coating process is of high importance to the pharmaceutical and food industry. The number of process variables and their interdependence in a pan coating process can make it a rather complex scale-up problem. This review discusses breaking down the coating process variables into three main categories: ...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章,评审
doi：10.1002/jps.24582
更新日期：2015-11-01 00:00:00
abstract：:Foam granulation is a relatively newer wet granulation process whereby foamed binder solutions are added to powders in a mixer. It is essential to understand the effect of powder substrate on foam drainage and half-life, which are relevant to nucleation and agglomeration during foam granulation. Hydroxypropyl methylce...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.23053
更新日期：2012-04-01 00:00:00
abstract：:An F(ab')2 fragment of an IgG has been spray-dried on a bench-top machine to examine the presence of insoluble particulates in the redissolved powder product. Preliminary experiments showed that treatment of the F(ab')2 in aqueous solution in a water bath at 65°C for 1 h produced fragmentation and also insoluble parti...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.23891
更新日期：2014-04-01 00:00:00
abstract：:The decomposition of a 1% dilution of nitrazepam in microcrystalline cellulose was established by quantitative determination of the two main breakdown products, 2-amino-5-nitrobenzophenone and 3-amino-6-nitro-4-phenyl-2(1H)-quinolone, using in situ diffuse reflectance measurements on thin-layer chromatograms. The deco...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600660517
更新日期：1977-05-01 00:00:00
abstract：:Polymer shielded liposomes were investigated as detoxifying agents for the weak bases imipramine and dosulepin and the diprotic drug opipramol. In vitro binding measurements in the presence of human serum samples revealed that the liposomes reduced the free drug concentration of the weak bases (corrected for protein b...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.21683
更新日期：2009-10-01 00:00:00
abstract：:The wettability of the (001), (100), and (011) crystallographic facets of macroscopic aspirin crystals has been experimentally investigated using a sessile drop contact angle (theta) method. theta for a nonpolar liquid was very similar for all three facets, though significant theta differences were observed for three ...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.20841
更新日期：2007-08-01 00:00:00
abstract：:The aim of this study was to investigate the role of porosity on the compression behavior and tablet tensile strength for granules produced by a dry granulation procedure. Microcrystalline cellulose was used as a typical pharmaceutical excipient and a comparison was made with the effect of granule porosity on the comp...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.24439
更新日期：2015-06-01 00:00:00
abstract：:(14)N nuclear quadrupole resonance (NQR) in two known polymorphs of famotidine was measured. At room temperature, seven quadrupolar sets of transition frequencies (ν(+), ν(-), and ν(0)) corresponding to seven different nitrogen sites in the crystal structure of each of the two polymorphs were found. This confirms the ...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.23956
更新日期：2014-09-01 00:00:00
abstract：:A semi-automated protein binding assay using equilibrium dialysis (ED) and a novel mixed-matrix methodology has been developed. This method decreases mass spectrometer run time and reduces the likelihood of experimental artifacts. In this cassette-based approach, a single matrix is prepared following dialysis by mixin...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.22188
更新日期：2010-12-01 00:00:00
abstract：:The capacity factors of several penicillins and cephalosporins, as well as those of 7-aminocephalosporanic acid, 6-aminopenicillanic acid, and 7-aminodeacetoxycephalosporanic acid, were determined at pH 2.5-7.5 with different methanol concentrations in the mobile phase. The influence of ionic strength on activity fact...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600690506
更新日期：1980-05-01 00:00:00
abstract：:Tritium-labeled progesterone was administered to mature female rats in the proestrous stage by three different routes, gastric intubation, subcutaneous injection, and uterine intraluminal instillation, to study the kinetics involved in the uptake and retention of radioactivity by the uterus and various other tissues. ...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600661223
更新日期：1977-12-01 00:00:00
abstract：:Daunorubicin (DAUN) and doxorubicin (DOX) are used to treat a variety of cancers. The use of DAUN and DOX is hampered by the development of cardiotoxicity. Clinical evidence suggests that patients with leukemia and Down syndrome are at increased risk for anthracycline-related cardiotoxicity. Carbonyl reductases and al...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1016/j.xphs.2016.03.013
更新日期：2016-06-01 00:00:00
abstract：:Carboxy group-terminated synthetic polymers--branched poly(ethylene glycol), poly(acryloylmorpholine), and poly(vinylpyrrolidone)--were made amphiphilic by derivatization with phosphatidyl ethanolamine via the terminal carboxy group and then incorporated into lecithin-cholesterol liposomes prepared by the detergent di...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600840904
更新日期：1995-09-01 00:00:00
abstract：:A pharmacokinetic model that permits prediction of aqueous humor pilocarpine levels following topical application to rabbit eyes was developed. The model is able to account for changes in both instilled solution volume and drug concentration. The model, although simplified, relies mainly on experimentally verifiable a...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600670507
更新日期：1978-05-01 00:00:00
abstract：:The advisability of a progressive curtailment of organic solvent film coating offers an incentive to develop latex systems. Here, the use of aqueous colloidal dispersions of cellulose acetate, plasticized with water-soluble additives, is proposed as an alternative way to obtain cellulose acetate membranes either by ca...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600760609
更新日期：1987-06-01 00:00:00
abstract：:In this work, a novel risk-based methodology for lot release is proposed. Its objective is to assess the risk that a lot declared to have passed truly meets product specifications. The methodology consists of 3 parts: adaptive sample size determination, estimation of the probability that the product was within specifi...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1016/j.xphs.2019.10.011
更新日期：2020-02-01 00:00:00
abstract：:Tissue damage caused by subcutaneous and intramuscular administration of three phenytoin prodrugs to rats was assessed. Since two of the prodrugs caused significant irritation, only 3-(hydroxymethyl)-5,5-diphenylhydantoin disodium phosphate ester might be useful as a nonirritant phenytoin prodrug suitable for parenter...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600730815
更新日期：1984-08-01 00:00:00
abstract：:A simple solution model that has lead to successful predictive equations for the partial molar excess properties of a solute in simple binary solvent mixtures containing only nonspecific interactions is extended to include association between the solute and one of the solvent components. An expression is derived and t...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600720822
更新日期：1983-08-01 00:00:00
abstract：:Multidrug resistance (MDR) mediated by the overexpression of the drug efflux protein P-glycoprotein is one of the major obstacles to successful cancer chemotherapy. The development of safe and effective MDR-reversing agents is an important approach to addressing this problem clinically. In this study, we evaluated the...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.22082
更新日期：2010-07-01 00:00:00
abstract：:Mathematical relationships describing the delivery of drug to a target organ after intra-arterial, intravenous, and oral administration are presented. This discussion clearly demonstrates that administration into a blood vessel leading to the target organ often is superior to intravenous administration. However, this ...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600701214
更新日期：1981-12-01 00:00:00
abstract：:Fifteen pyrimidine-related compounds were evaluated for their ability to inhibit enzymatic degradation of 5-fluoro-2'-deoxyuridine (FUdR). Acyclothymidine [5-methyl-1-(2'-hydroxyethoxymethyl)uracil] showed the highest inhibitory effect on the phosphorolytic degradation of FUdR in various tissue homogenates derived fro...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600771108
更新日期：1988-11-01 00:00:00
abstract：:Dogs were used to examine the effect of elevated gastric pH on the absorption of controlled-released theophylline dosage forms with pH-dependent dissolution. In vitro studies showed that a controlled-release theophylline tablet dissolved more rapidly if it was initially exposed to an acidic media. In contrast, a contr...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600770908
更新日期：1988-09-01 00:00:00
