Abstract:
:Prinomide tromethamine, a nonsteroidal antiinflammatory drug, was orally administered at doses of 250, 500, and 1000 mg every 12 hr for 28 days to healthy male volunteers. The pharmacokinetic behavior of prinomide and its primary plasma metabolite displayed nonlinear characteristics, while those of free prinomide and its metabolite were dose proportional. The nonlinear pharmacokinetic behavior of total prinomide and p-hydroxy metabolite was found to be caused by both saturable and mutually dependent competitive Langmuir-type plasma protein binding between prinomide and its p-hydroxy metabolite. The extent of the protein interaction displayed at steady state was due to the extensive accumulation of the p-hydroxy metabolite. While ligand-protein interactions are known for xenobiotic competitors, the characteristic behavior of prinomide is the first known example to be reported for a competitive protein interaction between a xenobiotic and its own in vivo generated metabolite. The findings of this study may have implications regarding the disposition of other extensively bound nonsteroidal antiinflammatory drugs with long-lived metabolites.
journal_name
Pharm Resjournal_title
Pharmaceutical researchauthors
Kochak GM,Pai S,Iannucci R,Honc F,Kachmar D,Perrino P,Egger Hdoi
10.1023/a:1018916811904subject
Has Abstractpub_date
1993-01-01 00:00:00pages
49-55issue
1eissn
0724-8741issn
1573-904Xjournal_volume
10pub_type
杂志文章abstract::We studied the effects of two verapamil analogs, anipamil and ronipamil, in traumatic shock. Noble-Collip drum trauma produced a shock state characterized by an eight-fold increase in plasma cathepsin D activity, a 13-fold increase in the rate of plasma myocardial depressant factor (MDF) accumulation, and a survival t...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/A:1016363316777
更新日期:1985-05-01 00:00:00
abstract::The synthesis of an homologous series of new water-soluble derivatives of pilocarpine is described. The new compounds, referred to as soft quaternary salts, are water soluble by virtue of a cationic ammonium head and their lipophilicity can be modulated by manipulating the size and the nature of the substituent in the...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1015847103862
更新日期:1992-03-01 00:00:00
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journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1018902404036
更新日期:1993-07-01 00:00:00
abstract:PURPOSE:The objective of this work was to assess, in vitro, the passage of P-glycoprotein dependent drugs across brain capillary endothelial cells, when these drugs are associated with a reversing agent. METHODS:An in vitro model of the blood-brain barrier consisting of a coculture of brain capillary endothelial cells...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1011913723928
更新日期:1998-07-01 00:00:00
abstract:PURPOSE:The purpose of the present study was to explore the involvement of indoxyl sulfate (IS) in nephrotoxicity and central nervous system (CNS) toxicity in cisplatin (CDDP)-treated rats. MATERIALS AND METHODS:Renal function was evaluated by serum creatinine and BUN levels. The IS levels in the serum, brain and kidn...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-006-9183-2
更新日期:2007-04-01 00:00:00
abstract:PURPOSE:To explore whether miR-19 is involved in the regulation of multidrug resistance (MDR), one of the main causes of breast cancer mortality, and modulates sensitivity of tumor cells to chemotherapeutic agents. METHODS:We analyzed miRNA expression levels in three MDR cell lines in comparison with their parent cell...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-011-0570-y
更新日期:2011-12-01 00:00:00
abstract::High molecular weight drugs in general, and peptides in particular, are usually delivered by parenteral route because they are poorly absorbed or degraded in the gastrointestinal tract. To optimize therapy, it is desirable to search for nonparenteral routes of administration and to deliver the drug in a controlled-rel...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1018948924992
更新日期:1993-06-01 00:00:00
abstract::Cyclosporine (CsA) is commercially available for oral administration as a solution in olive oil with alcohol and an emulsifier. To improve its variable absorption and low patient acceptability, several oral formulations were prepared and tested in vitro and in vivo in dogs. A tablet formulation prepared by direct comp...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1015815614959
更新日期:1991-04-01 00:00:00
abstract:PURPOSE:The aim of this work was to evaluate whether improved topical delivery of finasteride, focussed to the hair follicles of human scalp skin could be achieved with application of short durations of heat and use of specific chemical penetration enhancers. METHODS:Franz cell experiments with human scalp skin were p...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-020-02822-y
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abstract::Lidocaine was administered to healthy volunteers at different sites in the rectum. Unchanged drug and monoethylglycinexylidide (MEGX) concentrations were measured in plasma with a newly developed gas chromatographic method. Lidocaine was given rectally by means of an osmotic system (Osmet(®)) which delivered 25 mg/h a...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/A:1016380104424
更新日期:1984-05-01 00:00:00
abstract:PURPOSE:Monoamine oxidases (MAOs) are non-CYP enzymes that contribute to systemic elimination of therapeutic agents, and localized on mitochondrial membranes. The aim of the present study was to validate quantitative estimation of metabolic clearance of MAO substrate drugs using human liver microsomes (HLMs). METHODS:...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-017-2140-4
更新日期:2017-06-01 00:00:00
abstract::Sodium taurodihydrofusidate (STDHF) is one of the most promising absorption enhancers for nasal delivery of peptide drugs. Drugs and additives in nasal formulations should not interfere with the self-cleaning capacity of the nose by the ciliary epithelium. Measured in vitro on human adenoid tissue with a photoelectric...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1015872617511
更新日期:1990-02-01 00:00:00
abstract:PURPOSE:The specific interactions between three lectin-latex conjugates and different structures of rat intestinal mucosa have been studied ex vivo. METHODS:These systems were prepared by covalent coupling of different ligands, i.e., tomato lectin (TL), asparagus pea lectin (AL), mycoplasma gallisepticum lectin (ML), ...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1016405126656
更新日期:1996-11-01 00:00:00
abstract:PURPOSE:Since a previous qualitative study carried out by us showed the existence of an important influence of the particle size on the percolation thresholds and taking into account that the existing theoretical models can only provide qualitative explanation to this influence, the purpose of this work is to carry out...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1016088424993
更新日期:1996-03-01 00:00:00
abstract::Biotherapeutics, including recombinant or plasma-derived human proteins and antibody-based molecules, have emerged as an important class of pharmaceuticals. Aggregation and immunogenicity are among the major bottlenecks during discovery and development of biotherapeutics. Computational tools that can predict aggregati...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-011-0414-9
更新日期:2011-05-01 00:00:00
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journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-009-0020-2
更新日期:2010-02-01 00:00:00
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journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-005-6947-z
更新日期:2005-10-01 00:00:00
abstract:PURPOSE:The objective of this study was to evaluate nanoparticle uptake by the Caco-2 monolayer model in vitro. Special emphasis was placed on the localization and the quantification of the uptake of fluorescently labeled polystyrene and poly(lactic-co-glycolic acid) (PLGA) nanoparticles. METHODS:Intracellular fluores...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1015393710253
更新日期:2002-05-01 00:00:00
abstract:PURPOSE:To examine the inhibitory potential of enalapril [and other angiotensin converting enzyme (ACE) inhibitors] on glycylsarcosine (GlySar) transport by the high-affinity renal peptide transporter. METHODS:Studies were performed in rabbit renal brush border membrane vesicles in which the uptake of radiolabeled Gly...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1018847818766
更新日期:1999-05-01 00:00:00
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journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/b:pham.0000016251.42392.1e
更新日期:2004-02-01 00:00:00
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journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-009-0004-2
更新日期:2010-01-01 00:00:00
abstract::The role of a bile salt (sodium taurocholate) and lipolysis products (monoglyceride and fatty acid) in the intestinal absorption of a poorly water-soluble drug, diazepam, was investigated. Absorption rates and bioavailabilities were determined with the in situ rat gut technique of Doluisio et al. and analyzing the dia...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/A:1016312827680
更新日期:1985-09-01 00:00:00
abstract:PURPOSE:Covalent binding between N-acetyl-L-cysteine (NAC) and albumin was evaluated kinetically by conducting in vitro experiments. METHOD:After 14C-NAC was incubated with human or rat serum, the solution was analyzed by anion-exchange HPLC. The albumin-bound 14C-NAC was quantified by measuring the radioactivity in t...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1020749211745
更新日期:2002-11-01 00:00:00
abstract:PURPOSE:A Selegiline Transdermal System (STS) is under development for indications which may not be optimally or safely treated with oral selegiline. Studies were conducted to evaluate the in vitro penetration and skin metabolism of selegiline in order to better understand the toxicological findings and the observed pl...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1012051300130
更新日期:1997-01-01 00:00:00
abstract:PURPOSE:This study aims to develop a characterization method for coating structure based on image analysis, which is particularly promising for the rational design of coated particles in the pharmaceutical industry. METHODS:The method applies the MATLAB image processing toolbox to images of coated particles taken with...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-008-9805-y
更新日期:2009-04-01 00:00:00
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journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1012058323754
更新日期:1997-03-01 00:00:00
abstract:PURPOSE:To produce and characterize a nonviral ultrasound-controlled release system of plasmid DNA (pDNA) encapsulated in gas-filled poly(D,L-lactide-co-glycolide) microparticles (PLGA-MPs). METHODS:Different cationic polymers were used to form pDNA/polymer complexes to enhance the stability of pDNA during micropartic...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1014430631844
更新日期:2002-03-01 00:00:00
abstract:PURPOSE:Ultrasound can be used to release a therapeutic payload encapsulated within a perfluorocarbon (PFC) emulsion via acoustic droplet vaporization (ADV), a process whereby the PFC phase is vaporized and the agent is released. ADV-generated microbubbles have been previously used to selectively occlude blood vessels ...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-010-0277-5
更新日期:2010-12-01 00:00:00
abstract::The role of phosphatidylserine in the cellular and subcellular lung distribution of quinidine was investigated in rats, since quinidine was found to bind preferentially to phosphatidylserine. The concentration of phosphatidylserine in the cellular and subcellular fractions was determined after separation by two-dimens...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1015985511653
更新日期:1988-04-01 00:00:00
abstract:PURPOSE:This study aimed to investigate the impact of the size of X-ray iodinated contrast agent in nano-emulsions, on their toxicity and fate in vivo. METHODS:A new compound, triiodobenzoate cholecalciferol, was synthetized, formulated as nano-emulsions, and followed after i.v. administration in mice by X-ray imaging...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-015-1813-0
更新日期:2016-03-01 00:00:00