Abstract:
:The absorption, protein binding, blood-to-plasma ratio, renal excretion, and pharmacokinetics of the dopamine-2 agonists (D2-agonists) 4-(2-di-n-propylaminoethyl)-7-hydroxy-2-(3H)-indolone (1), N-(2'-hydroxy-5'-[N,N-di-n-propylaminoethylphenyl])methanesulfonamide (2), and 4-(2-di-n-propylaminoethyl)-2-(3H)-indolone (3) were examined in dogs and rats. On the basis of relative cumulative urinary recoveries of radiolabeled drug, all three compounds are well absorbed in rats and dogs. In dogs, the free fractions in plasma of unchanged 1, 2, and 3, determined by in vitro studies, were 74, 86, and 63%, respectively, and the protein binding was constant with increasing concentration. The blood-to-plasma partition ratios of the respective compounds were 1.22, 1.14, and 1.16 in dogs, and the ratios were constant with increasing concentration. Large differences between species (dogs, rats, and humans) in protein binding and blood-to-plasma ratios were not seen. The clearances (blood or plasma) of 1 and 2 in dogs were significantly greater than the clearance of 3. The clearance of 3 was almost exclusively nonrenal, whereas 13% of 1 and 2 were recovered unchanged in urine. The steady-state volumes of distribution and the distribution and elimination half-lives of the three compounds were not significantly different. Importantly, the mean residence time of 3 (147 min) in dogs was significantly longer than those of 1 (90 min) and 2 (96 min). The results of analogous studies in rats indicate that 1 and 2 are more rapidly metabolized than 3.
journal_name
J Pharm Scijournal_title
Journal of pharmaceutical sciencesauthors
Swagzdis JE,Wittendorf RW,DeMarinis RM,Mico BAdoi
10.1002/jps.2600751002subject
Has Abstractpub_date
1986-10-01 00:00:00pages
925-8issue
10eissn
0022-3549issn
1520-6017pii
S0022-3549(15)47246-6journal_volume
75pub_type
杂志文章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::Health authorities require that suitable stability of the drug substance be shown in relevant materials of construction. ICH Q1A(R2) explicitly states that "stability studies should be conducted on drug substance packaged in a container closure system that is the same as or simulates the packaging proposed for storage...
journal_title:Journal of pharmaceutical sciences
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doi:10.1016/j.xphs.2020.09.052
更新日期:2020-10-07 00:00:00
abstract::The aminoxyl (nitroxyl) labeled (2-chloroethyl)nitrosocarbamoyl (CNC) derivatives of amino acids, i.e., N-[[N'-(2-chloroethyl)-N'-nitrosoamino]carbonyl]-A-(1-oxy-2,2,6,6- tetramethylpiperidin-4-yl)amides, A = glycyl (10a), A = L-alanyl (10b), A = L-valyl (10c), A = L-phenylalanyl (10d), were synthesized and evaluated ...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600830715
更新日期:1994-07-01 00:00:00
abstract::The metabolic fate of aprophen hydrochloride (2-diethylaminoethyl 2,2-diphenylpropionate) was studied in rats after intravenous administration. Both 14C-labeled and unlabeled aprophen were used in these studies. Blood samples were collected and analyzed to determine the identities of the metabolites formed. Utilizing ...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600770210
更新日期:1988-02-01 00:00:00
abstract::Water/n-octanol partition coefficients (log P) for 33 1,2-dithiole-3-thiones and for 18 1,2-dithiol-3-ones were determined by RP-HPLC measurement of the concentration of the solute in aqueous solution after equilibrium. Depending on the nature of the substituents (alkyl or aryl) and their position(s) (4,5, or both) on...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600840914
更新日期:1995-09-01 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
abstract::Pancreatic islet transplantation is a promising advanced therapy that has been used to treat patients suffering from diabetes type 1. Traditionally, pancreatic islets are infused via the portal vein, which is subsequently intended to engraft in the liver. Severe immunosuppressive treatments are necessary, however, to ...
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abstract::Several amides of cyclic amines were prepared and tested as penetration enhancers in the diffusion of various drugs through hairless mouse skin in vitro. Hexamethylenelauramide (hexahydro-1-lauroyl-1H-azepine) was selected as a broad spectrum penetration enhancer worthy of further study. Later, the duration of the eff...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600751114
更新日期:1986-11-01 00:00:00
abstract::A number of arylidene derivatives of alicyclic ketones and some corresponding oximes, oxime esters, and related compounds were prepared as candidate cytotoxic agents. All of the compounds were evaluated against murine L1210 lymphoid leukemia cells. In general, cytotoxicity was greatest with the alpha,beta-unsaturated ...
journal_title:Journal of pharmaceutical sciences
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doi:10.1002/jps.2600830619
更新日期:1994-06-01 00:00:00
abstract::The effects of permeant charge (z) on iontophoretic-enhanced transport were investigated with synthetic Nucleopore membranes and with human epidermal membranes using a four-electrode potentiostat with side-by-side diffusion cells. The modified Nernst-Planck model (Nernst-Planck theory with an additional transport term...
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pub_type: 杂志文章
doi:10.1021/js960479m
更新日期:1997-06-01 00:00:00
abstract::The mechanism of organic solvent evaporation during microencapsulation and its role during microsphere hardening has been investigated. Evaporation and encapsulation studies were carried out in a jacketed beaker, filled with aqueous hardening solution, which was maintained at constant temperature and constant stirring...
journal_title:Journal of pharmaceutical sciences
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doi:
更新日期:1999-10-01 00:00:00
abstract::The relationship between chemical structure and antifungal activity of quaternary imidazolium compounds is analyzed. The compounds are described by a set of condition attributes concerning structure and by a decision attribute concerning activity. The description builds up an information system. The smallest set of co...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600840225
更新日期:1995-02-01 00:00:00
abstract::The stereoselective pharmacokinetics of suprofen enantiomers has been studied in humans by means of stable isotope-labeled pseudoracemate-diastereomer methodology. After a single oral dose of a near equimolar mixture of unlabeled-(R)-(-)- and [2H3]-(S)-(+)-suprofen [or unlabeled-(S)- and [2H3]-(R)-suprofen] to three h...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600801116
更新日期:1991-11-01 00:00:00
abstract::The purpose of this study was to examine the role of multidrug resistance-associated protein-1 and -2 (Mrp1 and Mrp2) in the efflux transport of organic anions across the blood-cerebrospinal fluid (CSF) barrier. The CSF concentration of estradiol-17beta-glucuronide (E(2)17betaG) and 2,4-dinitrophenyl-S-glutathione (DN...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.10521
更新日期:2004-01-01 00:00:00
abstract::Simple and sensitive enzyme immunoassays (EIAs), discriminating a new angiotensin-converting enzyme (ACE) inhibitor, cilazapril [9(s) - [1(s)-(ethoxycarbonyl)-3-phenylpropylamino]-octahydro-10-oxo-6H- pyridazo[1,2-a] [1,2]diazepine-1(s)carboxylic acid] and its active metabolite [9(s)-[1(s)-carboxy-3-phenylpropylamino]...
journal_title:Journal of pharmaceutical sciences
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doi:10.1002/jps.2600760308
更新日期:1987-03-01 00:00:00
abstract::Complexation of ferrous cytochrome P450 by metabolic intermediates formed during NADPH-catalyzed metabolism of compounds structurally related to orphenadrine was studied. This so-called metabolic intermediate complexation was determined in rat liver microsomes, obtained from phenobarbital-pretreated rats, at 455 nm us...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600730723
更新日期:1984-07-01 00:00:00
abstract::The tissue:plasma partition coefficients (Kp ) are good indicators of the extent of tissue distribution. Therefore, advanced tissue composition-based models were used to predict the Kp values of drugs under in vivo conditions on the basis of in vitro and physiological input data. These models, however, focus on animal...
journal_title:Journal of pharmaceutical sciences
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doi:10.1002/jps.24427
更新日期:2015-06-01 00:00:00
abstract::We report a semiquantitative method for determining trace amounts (<1%) of thermodynamically stable forms in polymorphic mixtures, focusing on sample preparation effects on solid phase transitions. Tegafur [5-fluoro-1-(oxolan-2-yl)-1,2,3,4-tetrahydropyrimidine-2,4-dione] was used as a model material in this study. The...
journal_title:Journal of pharmaceutical sciences
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doi:10.1002/jps.23323
更新日期:2012-12-01 00:00:00
abstract::Deflocculated suspensions of coarse powders tend to cake as the individual particles settle out and form compact, cohesive sediments. Limited flocculation results in looser sediments because the settled-out flocs incorporate large amounts of the liquid suspending medium. Controlled flocculation of bismuth subnitrate s...
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doi:10.1002/jps.2600650614
更新日期:1976-06-01 00:00:00
abstract::Complex dosing regimens simulated in the literature using a universal dosing regimen were calculated with a general dosing program developed using the program CONSAM. The program provides a rapid method of calculating nonuniform dosing regimens for up to n = 3 compartments for any linear model. Subject data can also b...
journal_title:Journal of pharmaceutical sciences
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doi:10.1002/jps.2600800406
更新日期:1991-04-01 00:00:00
abstract::A highly sensitive assay for the measurement of all-trans-retinoic acid (tretinoin) and 13-cis-retinoic acid (isotretinoin) has been developed. Collected plasma samples were protein precipitated with 2-propanol followed by solid phase extraction. The retinoic acids were subsequently derivatized to their pentafluoroben...
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pub_type: 杂志文章
doi:10.1021/js950339x
更新日期:1996-03-01 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::Nasal administration as a means of delivering therapeutic agents preferentially to the brain has gained significant recent interest. While some substrates appear to be delivered directly to the brain via this route, the mechanisms governing overall brain uptake and exposure remain unclear. Some substrates utilize the ...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章,评审
doi:10.1002/jps.20318
更新日期:2005-06-01 00:00:00
abstract::Biodegradable, dextran-based ion-exchange microspheres (IE-MS) have been used for localized delivery of anticancer drugs and chemosensitizers. Because of their hydrophilic nature, the IE-MS release their payload quickly. The purpose of this work was to develop an IE-MS system that could provide a broad range of releas...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/(SICI)1520-6017(200006)89:6<807::AID-JPS13
更新日期:2000-06-01 00:00:00
abstract::DNA co-condensates were formed by reacting [125I]DNA with an admixture of a high-mannose glycopeptide (Man9-CWK(18)) and either of two poly(ethylene glycol) peptides (PEG-VS-CWK(18) or PEG-SS-CWK(18)) followed by cross-linking with 6-50 mol equiv of glutaraldehyde. [125I]DNA co-condensates were administered intravenou...
journal_title:Journal of pharmaceutical sciences
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doi:10.1002/jps.1152
更新日期:2001-12-01 00:00:00
abstract::Progesterone release from monolithic devices prepared from various copolymers of poly(hydroxyethyl methacrylate) and poly(methoxyethoxyethyl methacrylate) or poly(methoxyethyl methacrylate) was examined. In general, plots of the fraction of drug released versus (time)1/2 were linear during the early stages of drug rel...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600700226
更新日期:1981-02-01 00:00:00
abstract::Hydrolytic degradation products of cefdinir were studied in acidic (pH 1), neutral (pH 6), and basic (pH 9) solutions. Seven major degradation products were isolated by preparative and/or high-performance liquid chromatography and characterized by UV, IR, 1H-NMR, and mass spectra. To clarify degradation pathways in ea...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1021/js950446r
更新日期:1996-09-01 00:00:00
abstract::The dissolution behavior and absorption of mefenamic acid following oral and rectal administration from drug:egg albumin solid dispersions have been studied in comparison with those of the drug alone. The interaction of drug with egg albumin in aqueous solution and solid state were examined by solubility analysis, dia...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600800517
更新日期:1991-05-01 00:00:00
abstract::The concentrations of antipyrine in plasma and saliva were equivalent in normal volunteers and in patients with acute viral hepatitis following oral doses of antipyrine. Estimates of clearance, volume of distribution, and half-life made from either plasma or saliva samples were not statistically different in these sub...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600660140
更新日期:1977-01-01 00:00:00
abstract::The effect of the oral dosing volume (DV) on both gastric emptying and intestinal absorption was examined by analyzing the gastrointestinal disposition of a model solute, L-glucose, in rats. The amount of 14C-labeled L-glucose in the gastric and intestinal contents of sacrificed rats was measured at various times afte...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.2600840417
更新日期:1995-04-01 00:00:00