Metabolism of carprofen, a nonsteroid anti-inflammatory agent, in rats, dogs, and humans.

Abstract:

:The metabolic disposition of 14C-labeled carprofen [(+/-)-6-chloro-alpha-methylcarbazole-2-acetic acid] was investigated in rats, dogs, and humans. Carprofen is eliminated predominantly by biotransformation in these three species. In dogs and rats, the direct conjugation of carprofen to form an ester glucuronide and oxidation to the C-7 and the C-8 phenols followed by their conjugation represent the major metabolic pathways. Small amounts of the alpha-hydroxy derivative also are formed by these species and are excreted free in the urine. In dogs, biliary secretion predominates, and 70% of an intravenous dose of carprofen is excreted in the feces while 8--15% of the dose is excreted in the urine. In rats, fecal excretion due to biliary secretion varies from 60 to 75%, and urinary excretion accounts for 20--30% of an intravenous dose. In humans direct conjugation of carprofen represents the only significant pathway of metabolism. Between 65 and 70% of the orally administered carprofen was found to be excreted as the ester glucuronide in the urine, and most of the remaining dose was estimated to be secreted as this metabolite in the bile. Due to enterohepatic circulation, only a fraction of the biliary metabolite was recovered in the feces in humans. Less than 5% of the dose was excreted in human urine as free, intact carprofen. In dogs and humans, plasma levels of carprofen and of total radioactivity exhibit a multiphasic decline. In the three human subjects studied, the terminal component declined with a 13--26 hr half-life; the terminal half-life was approximately 40 hr in dogs.

journal_name

J Pharm Sci

authors

Rubio F,Seawall S,Pocelinko R,DeBarbieri B,Benz W,Berger L,Morgan L,Pao J,Williams TH,Koechlin B

doi

10.1002/jps.2600691104

subject

Has Abstract

pub_date

1980-11-01 00:00:00

pages

1245-53

issue

11

eissn

0022-3549

issn

1520-6017

pii

S0022-3549(15)43447-1

journal_volume

69

pub_type

杂志文章
  • Relationship between molecular structure and cytochrome P450-metabolic intermediate complex formation, studied with orphenadrine analogues.

    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

    authors: Bast A,Savenije-Chapel EM,Noordhoek J

    更新日期:1984-07-01 00:00:00

  • Determination of a cephalosporin antibiotic, ceftibuten, in human plasma with column-switching high-performance liquid chromatography with ultraviolet detection.

    abstract::A column-switching high-performance liquid chromatographic assay combined with a heart-cutting technique and UV detection (LC/LC/UV) was developed to determine ceftibuten, a new oral cephalosporin, in human plasma. Plasma samples were directly injected into the first chromatographic column for sample cleanup and extra...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.2600810715

    authors: Pan HT,Kumari P,Lim J,Lin CC

    更新日期:1992-07-01 00:00:00

  • Synthesis of 10alpha-methoxy-delta8,9-lysergaldehyde from elymoclavine.

    abstract::A new synthesis is described for 10alpha-methoxy-delta8,9-lysergaldehyde involving the oxidation of elymoclavine with manganese dioxide in methanol. Lysergol and agroclavine provide no reaction under the same conditions. ...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.2600660937

    authors: Choong TC,Thompson BL,Shough HR

    更新日期:1977-09-01 00:00:00

  • In Vivo Performance of Fenofibrate Formulated With Ordered Mesoporous Silica Versus 2-Marketed Formulations: A Comparative Bioavailability Study in Beagle Dogs.

    abstract::The present study aims to evaluate the in vitro and in vivo performance of ordered mesoporous silica (OMS) as a carrier for the poorly water-soluble compound fenofibrate. Fenofibrate was loaded into OMS via incipient wetness impregnation to obtain a 29% drug load and formulated into capsules. Two capsule dosage forms ...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1016/j.xphs.2016.05.019

    authors: Bukara K,Schueller L,Rosier J,Daems T,Verheyden L,Eelen S,Martens JA,Van den Mooter G,Bugarski B,Kiekens F

    更新日期:2016-08-01 00:00:00

  • Phosphodiesterase inhibition by succinic and related acid biphenylalkyl monoesters.

    abstract::Biphenylalkyl monoesters of succinic and related acids represent a potent new class of cyclic AMP phosphodiesterase inhibitors. The biphenyl group is necessary for potent inhibition. The spatial relationship of the carboxyl and ester groups and alkyl chain length are important to inhibitory potency. ...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.2600680732

    authors: Rogers ME,Boots SG,Boots MR

    更新日期:1979-07-01 00:00:00

  • Drug delivery trends in clinical trials and translational medicine: evaluation of pharmacokinetic properties in special populations.

    abstract::In spite of the recent advances in technology to optimize the absorption, distribution, metabolism and elimination (ADME) properties of new and promising medicinal products to reduce clinical failures, the investigation of drug disposition in the pediatric and elderly populations continues to be under evaluated. With ...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章,评审

    doi:10.1002/jps.22253

    authors: Chien JY,Ho RJ

    更新日期:2011-01-01 00:00:00

  • Respirable form of crystals of cromoglycic acid.

    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

    authors: Chan HK,Gonda I

    更新日期:1989-02-01 00:00:00

  • Effect of Controlled Ice Nucleation on Stability of Lactate Dehydrogenase During Freeze-Drying.

    abstract::Several controlled ice nucleation techniques have been developed to increase the efficiency of the freeze-drying process as well as to improve the quality of pharmaceutical products. Owing to the reduction in ice surface area, these techniques have the potential to reduce the degradation of proteins labile during free...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1016/j.xphs.2017.10.020

    authors: Fang R,Tanaka K,Mudhivarthi V,Bogner RH,Pikal MJ

    更新日期:2018-03-01 00:00:00

  • Methionine, tryptophan, and histidine oxidation in a model protein, PTH: mechanisms and stabilization.

    abstract::Recent oxidation events on monoclonal antibody candidates prompted us to investigate the mechanism of oxidation of Met, Trp, and His residues and to search for suitable stabilizers. By using parathyroid hormone (1-34), PTH, as a model protein and various oxidants, aided by liquid chromatography, peptide mapping, and m...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.21746

    authors: Ji JA,Zhang B,Cheng W,Wang YJ

    更新日期:2009-12-01 00:00:00

  • InVitro, Ex Vivo, and In Vivo Evaluation of a Dual pH/Redox Responsive Nanoliposomal Sludge for Transdermal Drug Delivery.

    abstract::A dual pH/redox responsive copper-glyglycine-prednisolone succinate-loaded nanoliposomal (NL) sludge was successfully synthesized and optimized using a Box-Behnken design of experiments. Preformulation design variables indicated that relative ratios of phospholipids, considerably influences NL size, thus altering the ...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1016/j.xphs.2017.11.011

    authors: Mavuso S,Marimuthu T,Kumar P,Kondiah PPD,du Toit LC,Choonara YE,Pillay V

    更新日期:2018-04-01 00:00:00

  • Finding the Needle in the Haystack: High-Resolution Techniques for Characterization of Mixed Protein Particles Containing Shed Silicone Rubber Particles Generated During Pumping.

    abstract::During the manufacturing process of biopharmaceuticals, peristaltic pumps are employed at different stages for transferring and dosing of the final product. Commonly used silicone tubings are known for particle shedding from the inner tubing surface due to friction in the pump head. These nanometer sized silicone rubb...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1016/j.xphs.2020.12.002

    authors: Deiringer N,Haase C,Wieland K,Zahler S,Haisch C,Friess W

    更新日期:2020-12-09 00:00:00

  • Investigation of atypical dissolution behavior of an encapsulated amorphous solid dispersion.

    abstract::Poor dissolution performance is one of the challenges encountered in dosage form design of amorphous solid dispersions (ASDs). This study was aimed to investigate the effect of solid-liquid interactions of an encapsulated ASD on drug release. Drug release profiles of a molecularly interacting amorphous celecoxib solid...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.22462

    authors: Puri V,Dantuluri AK,Bansal AK

    更新日期:2011-06-01 00:00:00

  • Spatiotemporal Programing for the On-Demand Release of Bupivacaine Based on an Injectable Composite Hydrogel.

    abstract::We report a programed drug delivery system that can tailor the release of anesthetic bupivacaine in a spatiotemporally controlled manner. The drug delivery system was developed through the combination of a collagen-based injectable hydrogel and 2 types of poly(lactic-co-glycolic acid) (PLGA) particles. As a rapid-rele...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1016/j.xphs.2016.09.020

    authors: Dinh VV,Suh YS,Yang HK,Lim YT

    更新日期:2016-12-01 00:00:00

  • Evaluation of New Chemical Entities as Substrates of Liver Transporters in the Pharmaceutical Industry: Response to Regulatory Requirements and Future Steps.

    abstract::This article discusses the evaluation of drug candidates as hepatic transporter substrates. Recently, research on the applications of hepatic transporters in the pharmaceutical industry has improved to meet the requirements of the regulatory guidelines for the evaluation of drug interactions. To identify the risk of t...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章,评审

    doi:10.1016/j.xphs.2017.05.009

    authors: Okudaira N

    更新日期:2017-09-01 00:00:00

  • A potentiometric study of lithium complexation with catecholamines.

    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

    authors: Sandmann BJ,Luk HT

    更新日期:1986-01-01 00:00:00

  • Diffusion of nutrients molecules and model drug carriers through mucin layer investigated by magnetic resonance imaging with chemical shift resolution.

    abstract::Magnetic resonance imaging (MRI) with chemical shift resolution is a recent extension of MRI and it provides information about species resolved molecular transport on the macroscopic scale in complex systems. In this contribution, we show that by using this novel method, one can predict the behavior of drug and food m...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.20749

    authors: Lafitte G,Thuresson K,Söderman O

    更新日期:2007-02-01 00:00:00

  • Concomitant adsorption and stability of some anthracycline antibiotics.

    abstract::Using liquid scintillation counting and liquid chromatographic techniques, it has been demonstrated that the anthracycline antibiotics, doxorubicin hydrochloride, N-trifluoroacetyladriamycin-14-valerate, and N-trifluoroacetyladriamycin-14-octanoate, can be strongly absorbed to the walls of containers, depending on the...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.2600711011

    authors: Tomlinson E,Malspeis L

    更新日期:1982-10-01 00:00:00

  • Mechanism of action of retinyl compounds on wound healing IV: effect of desmethylretinoic acid and its vinylogs on granuloma formation.

    abstract::The effect of side-chain length of desmethylretinoic acid on granuloma formation induced by implantation of cotton pellets was studied. As in the homologous series of retinoic acid studies, compounds with side chains shorter than retinoic acid were not active while compounds with side chains as long or longer than ret...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.2600650425

    authors: Lee KH,Fu CC,Jung M

    更新日期:1976-04-01 00:00:00

  • Comparative pharmacokinetics of free muramyl tripeptide phosphatidyl ethanolamine (MTP-PE) and liposomal MTP-PE.

    abstract::The comparative pharmacokinetics of free MTP-PE (muramyl tripeptide phosphatidyl ethanolamine) and MTP-PE entrapped in negatively charged multilamellar liposomes (liposomal MPT-PE) was evaluated in rats at a bolus intravenous (i.v.) dose of 0.2 mg/kg and in dogs at a bolus i.v. dose of 0.1 mg/kg. Additional studies we...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.2600821005

    authors: Gay B,Cardot JM,Schnell C,van Hoogevest P,Gygax D

    更新日期:1993-10-01 00:00:00

  • Potentiation of the antitumor effect of 5-fluoro-2'-deoxyuridine esters in combination with acyclothymidine esters on L1210 in mice via oral administration.

    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

    authors: Kawaguchi T,Saito M,Saneyoshi M

    更新日期:1988-11-01 00:00:00

  • Influence of race or ethnicity on pharmacokinetics of drugs.

    abstract::Review of the current literature on racial differences in pharmacokinetics of drugs supports the premise that only pharmacokinetic processes which are biologically or biochemically mediated have the potential to exhibit differences between racial or ethnic groups. Thus, the pharmacokinetic factors which can be expecte...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章,评审

    doi:10.1021/js9702168

    authors: Johnson JA

    更新日期:1997-12-01 00:00:00

  • Simultaneous GLC determination of methyl salicylate and menthol in a topical analgesic formulation.

    abstract::A simultaneous GLC determination for methyl salicylate and menthol in a topical analgesic formulation is reported. n-Nonadecane is used as the internal standard. The method is rapid, accurate, precise, and selective in the presence of salicylic acid and ethyl salicylate. ...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.2600680431

    authors: Sapio JP,Sethachutkul K,Moody JE

    更新日期:1979-04-01 00:00:00

  • Effect of basic cholane derivatives on intestinal cholic acid metabolism: in vitro and in vivo activity.

    abstract::A representative series of hydroxy-5 beta-cholanyl-24-amines were tested both in vitro and in vivo with respect to their activity against the intestinal bacteria responsible for bile acid metabolism. For the in vitro studies, radiolabeled [14C]cholic acid was incubated with human stools both in aerobic and anaerobic c...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.2600810310

    authors: Roda A,Bellini AM,Mencini E,Minutello A,Fini A,Guarneri M

    更新日期:1992-03-01 00:00:00

  • Nanoscale surface characterization and miscibility study of a spray-dried injectable polymeric matrix consisting of poly(lactic-co-glycolic acid) and polyvinylpyrrolidone.

    abstract::Injectable controlled-release formulations are of increasing interest for the treatment of chronic diseases. This study aims to develop and characterize a polymeric matrix for intramuscular or subcutaneous injection, consisting of two biocompatible polymers, particularly suitable for formulating poorly soluble drugs. ...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.23131

    authors: Meeus J,Chen X,Scurr DJ,Ciarnelli V,Amssoms K,Roberts CJ,Davies MC,van Den Mooter G

    更新日期:2012-09-01 00:00:00

  • Determination of the chemical constituents and spectral properties of commercial and NF reference standard potassium guaiacolsulfonate: implications of the findings on compendial analytical methodology.

    abstract::HPLC analysis confirmed a difference in the chemical composition of commercial versus NF reference standard potassium guaiacolsulfonate. After separation by fractional crystallization, the two constituents comprising the former sample were identified by 1H-NMR as potassium guaiacol-4- and -5-sulfonate, respectively. T...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.2600730911

    authors: Tangtatsawasdi P,Krikorian SE

    更新日期:1984-09-01 00:00:00

  • A valid equation for the well-stirred perfusion limited physiologically based pharmacokinetic model that consistently accounts for the blood-tissue drug distribution in the organ and the corresponding valid equation for the steady state volume of distribu

    abstract::A consistent account of the assumptions of the well-stirred perfusion limited model leads to the equation for the organ tissue that does not coincide with that often presented in books and papers. The difference in pharmacokinetic profiles calculated by the valid and the commonly used equations could be quite signific...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.21798

    authors: Berezhkovskiy LM

    更新日期:2010-01-01 00:00:00

  • Pharmacokinetics of the antirheumatic proquazone in healthy humans.

    abstract::The pharmacokinetics of the antirheumatic proquazone and its conjugated and unconjugated m-hydroxy metabolites were investigated in five healthy male volunteers after both intravenous (75 and 122 mg) and peroral (300 and 900 mg via capsules) administration. For adequate intravenous dosing of the poorly water-soluble p...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.2600730312

    authors: Hinderling PH,Roos A

    更新日期:1984-03-01 00:00:00

  • Diffusion modeling of percutaneous absorption kinetics: 2. Finite vehicle volume and solvent deposited solids.

    abstract::The diffusion model for percutaneous absorption is developed for the specific case of delivery to the skin being limited by the application of a finite amount of solute. Two cases are considered; in the first, there is an application of a finite donor (vehicle) volume, and in the second, there are solvent-deposited so...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/1520-6017(200104)90:4<504::aid-jps1008>3.0

    authors: Anissimov YG,Roberts MS

    更新日期:2001-04-01 00:00:00

  • In vitro percutaneous absorption and in vivo protoporphyrin IX accumulation in skin and tumors after topical 5-aminolevulinic acid application with enhancement using an erbium:YAG laser.

    abstract::5-aminolevulinic acid (ALA) is used as a precursor of protoporphyrin IX (PpIX) for photodynamic therapy (PDT) of superficial skin cancers and subcutaneous metastases of internal malignancies. The permeability of ALA across intact skin is always low, making it difficult to achieve the desired therapeutic benefits. Henc...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.20577

    authors: Shen SC,Lee WR,Fang YP,Hu CH,Fang JY

    更新日期:2006-04-01 00:00:00

  • The Hypotonic Environmental Changes Affect Liposomal Formulations for Nose-to-Brain Targeted Drug Delivery.

    abstract::Systemic administration of drugs is ineffective in the treatment of central nervous system disorders because of the blood-brain barrier. Nasal administration has been suggested as an alternative administration route as drugs absorbed in the olfactory epithelium bypass the blood-brain barrier and reach the brain within...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1016/j.xphs.2019.03.006

    authors: Wu IY,Nikolaisen TE,Škalko-Basnet N,di Cagno MP

    更新日期:2019-08-01 00:00:00