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PubMed1981

Double-blind cross-over study of indoprofen versus ibuprofen and placebo in rheumatoid arthritis patients.

Thirty patients with classical or definite rheumatoid arthritis were given indoprofen 800 mg/day, ibuprofen 1200 mg/day or placebo in a double-blind cross-over trial, for three consecutive 10-day periods. The two drugs were both superior to placeto, intoprofen on more parameters than ibuprofen. Indoprofen was on the whole better than ibuprofen and the difference was statistically significant on pain, grip strength, morning stiffness, patients' preference and investigators' opinion of the therapeutic effect. Both drugs were well tolerated clinically.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1980

Pharmacokinetics and metabolism of indoprofen in the hamster.

2-[p-(1-Oxo-2-isoindolinyl)phenyl]propionic acid (indoprofen) is rapidly absorbed after oral administration (2 mg/kg) to male and female hamsters. Peak plasma levels of about 12-13 microgram/ml are reached within 1 h of dosing. Plasma concentrations in males and females are similar until 4 h but different at subsequent observation times. The half-life of indoprofen in plasma is approximately 7 h for males and 16 h for females. In experiments with 14C-labelled compound, radioactivity is mainly excreted in the urine: 94% of the dose in 6 days for males and 73% in 5 days for females. The females also excrete a significant amount of the drug (22%) in the faeces, probably via the bile. Residual radioactivity in female carcasses on the 5th day represents 1% of the dose. The main excretory product is the unchanged drug as such (about 35% and 21%, respectively, in 0-24 hour urine for males and females) and as glucuronic acid conjugate (29% and 12%). Small amounts of 5- and 6-hydroxy-isoindolinyl derivatives, and of two metabolites whose structures have not been identified, are also found in the urine of the animals of both sexes.

Animals↗
PubMed1981

Kinetics of indoprofen in patients with renal insufficiency (a preliminary report).

Plasma and urinary indoprofen concentrations were determined by liquid chromatography in healthy subjects and two patients with reduced glomerular filtration rate (GFR) of about 25 ml/min. The plasma half-life of the drug was prolonged in renal insufficiency. Until further studies have been performed indoprofen should be used with care in patients with renal impairment. Tentatively, the size of the dose or interval should be adjusted in proportion to the estimated preserved GFR.

Administration, Oral↗
PubMed1975

Indoprofen, a new analgesic and anti-inflammatory drug in cancer pain.

Evaluation of the analgesic activity of indoprofen was carried out in patients with cancer pain under double-blind conditions and compared with aspirin and placebo. A randomized experimental design was followed. Single oral doses were given of the test drug (100 and 200 mg), aspirin (600 and 1,000 mg), and placebo. For measuring analgesia, 5-point pain intensity and pain relief semiquantitative scales were used. Potency ratio between drugs was calculated on SPID (sum of pain intensity differences) and TOTPAR (total pain relief) and resulted in 10.3 by combination of estimates. In a group of only 24 patients, the data supported the following conclusions: indoprofen at 100 and 200 mg single doses is effective in relieving cancer pain; it displays a dose-related analgesic effect comparable to that of aspirin with only one-tenth the dose.

Adult↗
PubMed1977

GLC determination of indoprofen in plasma.

Implementation of human bioavailability studies with the analgesic indoprofen required a rapid, sensitive, and convenient assay in blood plasma. A procedure based on ether extraction of acidified plasma, derivatization with diazomethane, and GLC analysis using a 3% OV-1 column was sufficiently sensitive for measurement of plasma indoprofen concentrations in the 0.4-16 mug/ml range. An average recovery of 99.0 +/- 7.6% (SD) was achieved when the pentanoic acid homolog was employed as an internal standard.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1976

Indoprofen in the treatment of osteoarthrosis. A controlled trial in comparison with ibuprofen.

A controlled research has been carried out in 39 patients with osteoarthrosis in order to evaluate the efficacy of Indoprofen, a new analgesic-antiinflammatory compound. This product, a phenylpropionic acid derivative, was given by mouth at the dose of 600 mg daily for 7 days. For comparison a treatment with 900 mg daily of Ibuprofen for the same length of time was given to patients according to a double-blind cross-over experimental design. Significant decrease in overall pain intensity was observed together with significant improvement in motility. Indoprofen at the daily dose of 600 mg was comparable in efficacy with 900 mg of Ibuprofen in the relief of pain related to osteoarthrosis. Toleration of the drugs was very good.

Aged↗
PubMed1981

High-pressure liquid chromatographic determination of acetylsalicylic acid, salicylic acid, diflunisal, indomethacin, indoprofen and indobufen.

A high-pressure liquid chromatographic technique was developed which allowed concurrent measurement of acetylsalicylic acid (ASA) and salicylic acid (SA) in plasma. ASA was extensively deacetylated to SA not only in vivo but also in vitro, even in frozen plasma. The in vitro conversion could be prevented by physostigmine. In vivo, ASA was eliminated within few hours, whereas SA was continuously present following daily administration of conventional doses of ASA. A slight modification of a similar method, originally developed for naproxen determination [9], was found appropriate for measurement of the SA derivative diflunisal, of two non-SA antiinflammatory agents, indomethacin and indoprofen, and of a related anti-platelet agent, indobufen.

Anti-Inflammatory Agents↗
PubMed1986

Indoprofen-induced aplastic anemia in active connective tissue disease detected by drug-specific lymphocyte transformation.

In connective tissue diseases, the differentiation of disease-related hematological aberrations from drug-induced cytotoxic or allergic blood-cell dyscrasias is often difficult. In this paper we report on the positive identification of an indoprofen-induced severe pancytopenia in a multi-drug-treated patient with active systemic lupus erythematosus by use of a drug-specific lymphocyte transformation test.

Adult↗
PubMed2004

Indoprofen upregulates the survival motor neuron protein through a cyclooxygenase-independent mechanism.

Most patients with the pediatric neurodegenerative disease spinal muscular atrophy have a homozygous deletion of the survival motor neuron 1 (SMN1) gene, but retain one or more copies of the closely related SMN2 gene. The SMN2 gene encodes the same protein (SMN) but produces it at a low efficiency compared with the SMN1 gene. We performed a high-throughput screen of approximately 47,000 compounds to identify those that increase production of an SMN2-luciferase reporter protein, but not an SMN1-luciferase reporter protein. Indoprofen, a nonsteroidal anti-inflammatory drug (NSAID) and cyclooxygenase (COX) inhibitor, selectively increased SMN2-luciferase reporter protein and endogenous SMN protein and caused a 5-fold increase in the number of nuclear gems in fibroblasts from SMA patients. No other NSAIDs or COX inhibitors tested exhibited this activity.

Animals↗
PubMed2005

Comparative study of the photophysical properties of indoprofen photoproducts in relation with their DNA photosensitizing properties.

The photophysical properties of indoprofen photoproducts have been examined in various solvents by absorbance and emission spectroscopies in relation with their photosensitizing properties. The photophysical properties of 2-[4-(1-hydroxy)ethylphenyl]isoindolin-1-one (HOINP) and 2-(4-ethylphenyl)isoindolin-1-one (ETINP) are typical of a singlet excited state when the ones of 2-(4-acetylphenyl)isoindolin-1-one (KINP) are based on its triplet excited state according to previous work. The effect of solvent polarity on the absorption and fluorescence properties of HOINP and ETINP has been investigated as a function of Delta f, the Lippert solvent polarity parameter. A solvatochromic effect, function of the polarity region, has been observed for both photoproducts due to a change in the dipole moment of the compound upon excitation. In low-polarity regions, the excited state dipole moment of HOINP undergoes only a moderate increase (11.5 D) as compared to the dipole moment of the ground state (4.5 D) suggesting that the fluorescence arises from the locally excited state while in high-polarity regions it is strongly increased (42.9 D), which can imply that the emission takes place from a charge transfer state. In the case of ETINP, it would seem that the emitting state is rather a charge transfer state whatever the region is (16.9 and 31.8 D for the calculated excited-state dipole moments in the low and high-polarity regions, respectively). HOINP and ETINP do not produce thymine dimers by photosensitization but induce photooxidative damage via an electron transfer mechanism.

DNA↗
PubMed1981

How frequently should anti-inflammatory drugs be given? A study with indoprofen.

Indoprofen, despite its relatively short plasma half-life, was just as effective given twice daily as when the same daily total was given in four divided doses. There was a trend in favour of the twice daily regime for changes in morning pain and the duration of morning stiffness. Preferences were equally divided between the two regimes and efficacy was the usual reason for patients preferring one or other. Side-effects were no more frequent with the twice daily regime. Pharmacokinetics are no substitute for clinical experiment in planning the dosage regime of a non-steroidal anti-inflammatory drug.

Arthritis, Rheumatoid↗
PubMed1994

Non-steroidal anti-inflammatory drugs. III. Structure of indoprofen: 2-[4-(1-oxo-2-isoindolinyl)phenyl]propionic acid.

Indoprofen, 4-(1,3-dihydro-1-oxo-2H-isoindol-2-yl)-alpha-methylbenzeneaceti c acid, C17H15NO3, a non-steroidal anti-inflammatory agent, falls into the class of phenylpropionic acids that includes ibuprofen, ketoprofen and flubirprofen. It adopts a planar conformation apart from the carboxylic acid group. There is a small twist of 8.8 (2) degrees between the mean planes of the isoindolinyl and phenyl rings. The rotation of the carboxyl group out of the plane of the adjacent phenyl ring seems to be connected with anti-inflammatory activity and is similar to that found in other 2-phenylpropionic acids. A pair of intermolecular hydrogen bonds connects two carboxylic acid groups across a centre of symmetry with an O...O distance of 2.61 (1) A.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1985

Stereoselective disposition of indoprofen in surgical patients.

The pharmacokinetics of the enantiomers of indoprofen were determined after intravenous administration of the racemate to 10 surgical patients. The mean volume of distribution was 8.97 +/- 2.21 (s.d.) 1 for the pharmacologically active S(+)-enantiomer and 12.60 +/- 4.21 1 for the R(-)-enantiomer (P less than 0.001). The corresponding values for clearance were 32.2 +/- 11.1 ml min-1 and 48.8 +/- 15.5 ml min-1 (P less than 0.001). There was no significant difference in mean terminal half-life between the enantiomers.

Adult↗
PubMed1986

Pharmacokinetic profile of indoprofen in elderly subjects.

Multiple dosing four times daily for 7 days of indoprofen 200 mg, a non-steroidal anti-inflammatory drug with a short half-life (t1/2), revealed drug accumulation in eight elderly subjects. This indicates a substantially longer t1/2 (11 h) than that reported in young persons (3 h). A reduction in dose compared to younger subjects is recommended in elderly patients with osteoarthritis.

Aged↗
PubMed1982

Effects of intravenous indoprofen on bleeding time and other haemostatic parameters.

The influence of i.v. administration of indoprofen on template bleeding time and other haemostatic parameters was investigated in ten elderly subjects with osteoarthritis. The drug was given first as a single dose (400 mg bolus) and then, after an appropriate interval, as a short-term treatment (200 mg bolus t.i.d. for 7 days). Platelet count, prothrombin time and partial thromboplastin time were never affected, whereas a significant, though moderate, lengthening of bleeding time and a parallel reduction of platelet aggregation were observed in both trials. In the acute one these changes were seen at the first hour following administration and waned in all patients within 96 hours. In the subacute test the bleeding time was steadily prolonged throughout the week of treatment, being slightly still above the baseline value 7 days later, at which time no residual effects were noticeable in platelet aggregation.

Aged↗
PubMed1979

Indoprofen, a new non-steroidal anti-inflammatory drug, in the treatment of osteoarthrosis: report on a multi-centre study in 1629 patients.

A multi-centre trial was carried out in 1629 patients with osteoarthrosis in 233 clinical centres to investigate the therapeutic efficacy and tolerability of indoprofen in this clinical condition. The results from assessments of both subjective and objective variables were comparable to those obtained in Phase 3 studies. Moreover, 87.2% of patients expressed a 'good' or 'very good' opinion on the product's efficacy after treatment, usually with 3 tablets (600 mg) daily for 4 weeks. The benefit/risk relationship was confirmed as very favourable on account of the marked activity of the drug and the acceptable frequency of adverse reactions, which were mainly subjective and slight and confined to the gastro-intestinal tract.

Adult↗
PubMed2003

Photochemical and photophysical properties of indoprofen.

The photophysical properties and photochemistry of indoprofen (INP) have been investigated. Absorption and emission spectroscopies in phosphate buffer, ethanol and ether show that INP photophysics is dominated by a singlet-singlet transition of pipi* character. INP fluoresces at room temperature, with a quantum yield approximately 0.04. Flash photolysis experiments together with the lack of phosphorescence at room temperature point to a very weak intersystem crossing. The photoreactivity of INP is centered on the propionic acid chain and gives rise to photoproducts similar to those obtained with other arylpropionic acids (ethyl, hydroxyethyl and acetyl derivatives). Thus, irradiation of INP in aqueous buffer results in photodecarboxylation and leads mainly to oxidative compounds whose proportions increase with increasing oxygen concentration. These data suggest a photoreactivity occurring from the excited singlet state.

Cyclooxygenase Inhibitors↗
PubMed1988

Transsynovial kinetics of indoprofen in patients with rheumatoid arthritis and cyclooxygenase-inhibition in vitro.

Twenty-four patients suffering from rheumatoid arthritis and requiring articular punctures were treated with 200 mg of indoprofen thrice daily for four days. The subjects were divided into four groups each of six patients. Following the last dose, blood and synovial fluid samples were taken simultaneously according to different time schedules. Maximum plasma levels of 17.5 micrograms/ml were observed after 2.5 h. Peak synovial fluid concentrations amounted to 8.1 micrograms/ml 4 h following the last dose. Elimination from synovial fluid occurred at 10.6 h compared to 9.3 h from plasma. Free synovial fluid levels of approximately 50 ng/ml are in the range of concentrations necessary for cyclooxygenase inhibition in mouse peritoneal macrophages.

Arthritis, Rheumatoid↗