E Cavalletti

Cell Therapeutics, Inc., Seattle, Washington, United States

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Publications (28)72.58 Total impact

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    ABSTRACT: Anthracyclines and anthracenediones are important oncotherapeutics; however, their use is associated with irreversible and cumulative cardiotoxicity. A novel aza-anthracenedione, pixantrone (BBR 2778), was developed to reduce treatment-related cardiotoxicity while retaining efficacy. This study evaluates the cumulative cardiotoxic potential of pixantrone compared with equiactive doses of doxorubicin and mitoxantrone in both doxorubicin-pretreated and doxorubicin-naïve mice. CD1 female mice were given doxorubicin 7.5 mg/kg (once weekly for 3 weeks) followed 6 weeks later by either sterile 0.9% saline, doxorubicin 7.5 mg/kg, pixantrone 27 mg/kg, or mitoxantrone 3 mg/kg (once weekly for 3 weeks). A second group of CD1 female mice were given 2 cycles of either sterile 0.9% saline, pixantrone 27 mg/kg, doxorubicin 7.5 mg/kg, or mitoxantrone 3 mg/kg (once weekly for 3 weeks). Animals were sacrificed at different time points for histopathologic examination of the heart. In the doxorubicin-pretreated mice, further exposure to doxorubicin or mitoxantrone resulted in a significant worsening of pre-existing degenerative cardiomyopathy. In contrast, pixantrone did not worsen pre-existing cardiomyopathy in these animals. Only minimal cardiac changes were observed in mice given repeated cycles of pixantrone, while 2 cycles of doxorubicin or mitoxantrone resulted in marked or severe degenerative cardiomyopathy. These animal studies demonstrate the reduced cardiotoxic potential of pixantrone compared with doxorubicin and mitoxantrone. Exposure to pixantrone did not worsen pre-existing cardiomyopathy in doxorubicin-pretreated mice, suggesting that pixantrone may be useful in patients pretreated with anthracyclines.
    No preview · Article · Jul 2007 · Investigational New Drugs
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    ABSTRACT: Pixantrone is an immunesuppressor similar to mitoxantrone but with lower cardiotoxicity. We evaluated the effect of pixantrone on B cells and lymphomononuclear cells in the course of acute EAE. Pixantrone reduced the number of B cells and suppressed myelin basic protein (MBP) specific IgG production. In vitro, pixantrone induced apoptosis of rat B lymphocytes in a way similar to mitoxantrone. In addition, pixantrone inhibited antigen specific and mitogen induced lymphomononuclear cell proliferation, as well as IFN-gamma production, during EAE. These findings suggest a similar mechanism of action for pixantrone and mitoxantrone on the effector function of lymphomonocyte B and T cells.
    No preview · Article · Dec 2005 · Journal of Neuroimmunology
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    ABSTRACT: Pixantrone is less cardiotoxic and is similarly effective to mitoxantrone (MTX) as an antineoplastic drug. In our study, pixantrone reduced the severity of acute and decreased the relapse rate of chronic relapsing experimental allergic encephalomyelitis (EAE) in rats. A marked and long-lasting decrease in CD3+, CD4+, CD8+ and CD45RA+ blood cells and reduced anti-MBP titers were observed with both pixantrone and MTX. In vitro mitogen- and antigen-induced T-cell proliferation tests of human and rodents cells evidenced that pixantrone was effective at concentrations which can be effectively obtained after i.v. administration in humans. Cardiotoxicity was present only in MTX-treated rats. The effectiveness and the favorable safety profile makes pixantrone a most promising immunosuppressant agent for clinical use in multiple sclerosis (MS).
    No preview · Article · Jul 2004 · Journal of Neuroimmunology
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    ABSTRACT: With the aim to provide second-generation anthracenedione analogues endowed with reduced side effects and a wider spectrum of action than mitoxantrone and doxorubicin, a large number of new molecules bearing nitrogen atoms in the chromophore was synthesized and screened in vitro and in vivo. From this screening, BBR 2778 (6,9-bis[(2-aminoethyl)amino] benzo[g]isoquinoline-5,10-dione dimaleate) emerged as the most interesting compound. BBR 2778 was tested in vitro on several murine and human tumor cell lines and showed cytotoxic potency lower than that of mitoxantrone and doxorubicin. BBR 2778 was more cytotoxic in leukemia and lymphoma cell lines than in solid tumor cell lines. Although against in vivo models BBR 2778 was less potent than mitoxantrone and doxorubicin, its antitumor activity was equal or superior (in certain tumor models) to that of the above standard compounds. In particular, BBR 2778 was curative against L1210 murine leukemia and YC-8 murine lymphoma. Moreover, it showed an antitumor activity comparable to that of mitoxantrone and doxorubicin on solid tumors. No cardiotoxic effect of BBR 2778 in animals not pretreated with anthracyclines was observed compared to standards. In light of its spectrum of activity and marked efficacy against lymphomas and leukemias over a wide dose range, together with its lack of delayed cardiotoxicity, BBR 2778 has been entered in clinical studies.
    No preview · Article · Nov 2001 · Tumori
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    ABSTRACT: The issue of dimethylsulfoxide (DMSO) neurotoxicity is an important one, given its wide use in experimental toxicology as a solvent for hydrophobic substances. We examined the effect of the intraperitoneal administration of different DMSO solutions (1.8-7. 2%) on the peripheral nervous system of Wistar rats treated for 10 consecutive days and followed-up for an additional 45 days. DMSO administration induced a dose-dependent reduction in nerve conduction velocity, with complete recovery occurring in the follow-up. No structural changes were found in the sciatic nerve at 1.8% and 3.6% DMSO concentrations, suggesting that the mechanism of action of DMSO involves a functional impairment (i.e. conduction block) similar to that already described for this substance in isolated systems. However, when DMSO was administered at the 7.2% concentration, evident structural changes were observed in the sciatic nerve, with myelin disruption and uncompacted myelin lamelle. The neurophysiological and pathological changes observed in our study are severe enough to merit careful consideration in the course of experimental studies involving DMSO as a solvent for drugs which are under evaluation for their potential neurotoxicity.
    Full-text · Article · Jan 2001 · Toxicology Letters
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    ABSTRACT: Multinuclear platinum complexes represent a new class of anticancer agents, distinct in terms of DNA binding features and the profile of antitumor activity from their mononuclear counterparts, in particular cisplatin. Among complexes of this class, BBR 3464, a trinuclear platinum compound has been selected for preclinical development. In the present study, we describe the preclinical evaluation of BBR 3464 in a series of human tumor cell lines and tumor xenografts, with special emphasis on tumor types known to be resistant to cisplatin. In a panel of seven human tumor cell lines naturally resistant to cisplatin (three ovarian and four melanomas), BBR 3464 was extremely potent with IC50 values at least 20-fold lower than cisplatin. Against eight human tumor xenografts including four tumors refractory to cisplatin, BBR 3464 was confirmed to be very active with a tumor weight inhibition >80% in seven of them. The efficacy of BBR 3464 against cisplatin-resistant tumors was consistent with the ability of the drug to completely overcome resistance in three cell systems characterized by acquired resistance to cisplatin. Moreover, BBR 3464 caused a more prolonged effect than cisplatin, which was reflected by higher specific growth delay values. This prolonged effect is likely to be related to a more persistent perturbation of the cell cycle induced by BBR 3464 than by cisplatin, as shown in one ovarian tumor cell line. Finally, the profile of sensitivity to BBR 3464 within the 60-cell-lines screening panel of the National Cancer Institute, NIH (Bethesda, MD) differed from those of established drugs, thus supporting the hypothesis of a distinct mechanism of cytotoxic activity of BBR 3464. The novel trinuclear platinum complex, in light of its innovative antitumor activity profile, has the potential to become a useful clinical agent for the treatment of unresponsive tumors.
    No preview · Article · Aug 2000 · Clinical Cancer Research
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    ABSTRACT: The distribution of paclitaxel (Taxol) within the central and peripheral nervous system after repeated administration of this antineoplastic agent is still largely unknown. In this study we determined for the first time paclitaxel tissue concentration in the brain, spinal cord, dorsal root ganglia (DRG) and sciatic nerve using an experimental paradigm in the rat which reproduces the features of paclitaxel peripheral neurotoxicity in humans. Pathological confirmation of the onset of paclitaxel-induced peripheral neurotoxicity was performed. In order to achieve reliable results even with low concentrations of paclitaxel, a newly reported analytical method (high-performance liquid chromatography with tandem mass spectrometry) was used. We demonstrated that paclitaxel has easy access to the DRG, where it accumulates, while the lowest concentrations of the drug were measured in the brain. The intermediate concentrations of paclitaxel observed in the sciatic nerve and spinal cord may be due to paclitaxel transport along the centrifugal and centripetal branches of the DRG neuron axons.
    Full-text · Article · Jul 2000 · NeuroToxicology
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    E Scanziani · A Gobbi · L Crippa · A M Giusti · E Pesenti · E Cavalletti · M Luini
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    ABSTRACT: Hyperkeratosis-associated coryneform (HAC) is a coryneform bacterium, with a biochemical profile similar to Corynebacterium bovis, that causes hyperkeratotic dermatitis in athymic nude mice. In the present study 28 severe combined immunodeficient (SCID) mice coming from six different animal facilities were submitted for bacteriological and pathological examination. HAC was isolated from 10 SCID mice belonging to two of these facilities. Two of the HAC-infected mice showed macroscopical lesions consisting in large alopecic areas, with small white flakes, involving the dorsum, flanks, neck and cheeks. Histologically, the skin of these animals was characterized by diffuse acanthosis and hyperkeratosis. In the other eight HAC-infected SCID mice no macroscopical lesions were observed but focal areas of minimal to mild acanthosis were histologically detected in five cases. These results suggest that HAC can infect SCID mice inducing skin lesions similar, although generally less severe, to those observed in nude mice with hyperkeratotic dermatitis. Our results pointed out that SCID mice may play an important role in the epidemiology of hyperkeratotic dermatitis of athymic nude mice.
    Full-text · Article · Aug 1998 · Laboratory Animals
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    E Scanziani · A Gobbi · L Crippa · A M Giusti · R Giavazzi · E Cavalletti · M Luini
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    ABSTRACT: Hyperkeratotic dermatitis of athymic nude mice is an infectious disease caused by a coryneform bacterium. During the spring of 1995, outbreaks of hyperkeratotic dermatitis were observed in several nude mice facilities in northern Italy. In this report we describe the clinical, histopathological and microbiological features of the disease in two different animal facilities. Affected animals showed a typical 'scaly' appearance with small white flakes of material adherent to the skin. In one of the outbreaks (facility 2) the lesions were less severe and involved only limited areas of the body. The infection spread very quickly and the morbidity reached more than 80% in a few days, while the mortality was about 1%. The lesions resolved spontaneously within 7-10 days. Histological examination of affected skin revealed orthokeratotic hyperkeratosis, acanthosis and dermal inflammatory infiltration which were more severe in mice from facility 1. In Gram-stained sections groups of rods consistent with coryneform bacteria were detectable in the keratin layers covering the epidermal surface. A coryneform bacterium, biochemically typed as Corynebacterium bovis, was isolated from 11 out of 11 mice from facility 1 and from 8 out of 11 mice from facility 2.
    Full-text · Article · Aug 1997 · Laboratory Animals
  • L Crippa · A M Giusti · G Sironi · E Cavalletti · E Scanziani

    No preview · Article · May 1997 · Laboratory animal science
  • G Cavaletti · E Cavalletti · P Montaguti · N Oggioni · O De Negri · G Tredici
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    ABSTRACT: The effectiveness of paclitaxel (Taxol) in the treatment of different tumors is well-known but, on the other hand, there is little information regarding its neurotoxicity and the mechanism(s) underlying this potentially severe side effect. In this study, using behavioral, neurophysiological, morphological and morphometric methods, we evaluated the effect of intravenous administration of paclitaxel on the rat nervous system. After 2 pilot studies, 40 female Wistar rats were treated with intravenous paclitaxel via a catheter placed in the jugular vein, while 20 animals were used as controls. Paclitaxel dissolved in ethanol/Tween 80/saline (5/5/90%) was administered 5 times over a period of 10 days. At the end of the experiment half the surviving animals in each group were evaluated and sacrificed (day 11), while the rest of the rats were evaluated and sacrificed on day 25. On day 11 the treated animals had significant impairment in pain perception (tail-flick test), coordination (rota-rod test) and nerve conduction velocity in the tail nerve. At the light microscope minimal axonal damage and Schwann cell activation were observed in the sciatic nerve. At the electron microscope microtubular accumulation was present within the axon in dorsal and ventral spinal roots and in the sciatic nerve. On day 25 the behavioral tests were normal in treated rats, while the nerve conduction velocity was still moderately reduced in comparison with the controls. At the electron microscope a morphological examination evidenced that microtubular accumulation was less severe, but still evident, especially in the sciatic nerve. Morphometric determinations performed on days 11 and 25 did not evidence differences between paclitaxel-treated rats and controls. The results of this study, the first in which an extended examination of the nervous system of animals treated intravenously with paclitaxel has been carried out, suggest that short-term administration of the drug induces mainly reversible changes in the peripheral nerves and spinal roots. Microtubules seem to be the main target of paclitaxel neurotoxicity, in much the same way as has been described for its antineoplastic activity. Finally, no pathological changes were seen in the neuronal bodies of the spinal cord and dorsal root ganglia. This model may be used for further studies with combination treatments with other antineoplastic or neuroprotective agents.
    No preview · Article · Feb 1997 · NeuroToxicology
  • E Cavalletti · P Montaguti · F Sala · R Ceserani
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    ABSTRACT: Moguisteine (R,S(+/-)-2-(2-methoxyphenoxy)-methyl-3-ethoxycarbonylacetyl-1,3-t hiazolidine, CAS 119637-67-1), a new peripheral non-narcotic antitussive drug, is a racemate composed of an equimolar mixture of R(+) and S(-) enantiomers (BBR 2221 and BBR 2222, respectively). Since in some cases the use of only one enantiomer instead of a racemate may increase the efficacy and/or the tolerability of a compound, moguisteine enantiomers were submitted to toxicological evaluation. Given in a single oral (gavage) or intraperitoneal administration to mice and rats, both moguisteine enantiomers show very low general toxicity. Administered by gavage to rats and dogs for four consecutive weeks, BBR 221 and BBR 2222 are tolerated at up to the dose of 240 mg/kg/day in both sexes with no appreciable toxic changes. Finally, the mutagenicity tests show that both enantiomers are devoid of any mutagenic potential both in vitro and in vivo. Considering the overall results of the toxicological studies and comparing them with the data obtained from the previously performed studies with the racemate moguisteine, it can be affirmed that no differences can be identified between the two enantiomers and the racemate moguisteine. These findings justify the development of moguisteine as a racemate since neither enantiomer should offer any advantage over the racemate.
    No preview · Article · Jan 1997 · Arzneimittel-Forschung
  • L Gallico · A Borghi · E Cavalletti · R Ceserani · S Tognella
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    ABSTRACT: The antitussive effect of the R-(+)- and S-(-)-enantiomers of moguisteine were evaluated in comparison with the racemate in cough induced by 7ṁ5% citric acid and 30 μM capsaicin aerosol in conscious guinea-pigs. No difference in potency was observed between moguisteine and the enantiomers. The oral ED50 values (with 95% confidence limits) for moguisteine, R-(+)- and S-(-)-enantiomers were respectively: 20ṁ4 (12ṁ9−26ṁ6), 20ṁ9 (14ṁ9−26) and 21ṁ6 (11ṁ8−30ṁ0) mg kg−1 in cough provoked by citric acid and 17ṁ7 (12ṁ5−29ṁ8), 18ṁ9 (14ṁ1−30ṁ1) and 20ṁ5 (15ṁ1−36ṁ6) mg kg−1 in cough induced by capsaicin. The acute oral and intraperitoneal toxicities of the enantiomers and moguisteine in the rat are very similar. These findings suggest that the use of either enantiomer does not offer any advantage over the racemate.
    No preview · Article · Feb 1996 · Journal of Pharmacy and Pharmacology
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    ABSTRACT: Interstitial nephritis was seen histologically in 19 (59%) out of 32 pure-breed beagle dogs (16 males and 16 females) subjected to standard safety tests. In these animals no clinical abnormalities were observed and all the tested parameters (haematology, biochemistry and urine analysis) were within the normal ranges. Leptospiral antibody titres ranging from 1 : 100 to 1 : 6400, against a serovar (hardjo) belonging to the Sejroe serogroup, were detected by the microscopic agglutination test (MAT) in the serum of the 19 dogs with interstitial nephritis. All animals without renal lesions were seronegative. Leptospiral antigen was detected immunohistochemically in the kidneys of 4 dogs; leptospires were detected in Warthin-Starry stained sections of one dog. Leptospires were isolated from the kidneys of 3 of the 4 dogs examined by bacterial culture. The isolated strains were typed as serovar sejroe by restriction endonuclease digestion and Southern blot hybridization analysis of their DNA. It was concluded that Leptospira interrogans serovar sejroe, was responsible for an asymptomatic chronic renal infection which was widespread in this group of laboratory dogs.
    Full-text · Article · Aug 1995 · Laboratory Animals
  • P Montaguti · R Ceserani · R Bussi · E Cavalletti · S Tognella
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    ABSTRACT: Moguisteine (R,S(+/-)-2-(2-methoxyphenoxy)-methyl-3-ethoxycarbonylacetyl- 1,3-thiazolidine, CAS 119637-67-1), a new oral non narcotic peripherally acting antitussive drug, was examined for effects in the rat on general reproductive performance (at 0, 50, 212, 900 mg/kg/d,) for embryotoxicity (at 0, 25, 75, 225, 900 mg/kg/d) and for peri-postnatal toxicity (at 0, 62.5, 250, 1000 mg/kg/d). Embryotoxicity (at 0, 75, 225, 900 mg/kg/d) was also examined in the New Zealand White rabbit. In all the studies, moguisteine was administered orally as a suspension by gavage. At the tested doses, moguisteine did not interfere with general reproductive performance, either in the F0 or in the F1 generation. The drug did not show any toxic effect on the dams and their fetuses, nor did it have any teratogenic effect in either of the tested species. Finally, moguisteine had no adverse effects, either on parturition or on peri-and postnatal survival and/or development of the offspring.
    No preview · Article · Jan 1995 · Arzneimittel-Forschung
  • E Cavalletti · R Ceserani · F Sala · P Montaguti · S Tognella
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    ABSTRACT: Moguisteine (R,S(+/-)-2-(2-methoxyphenoxy)-methyl-3-ethoxycarbonylacetyl- 1,3-thiazolidine, CAS 119637-67-1), a new oral non-narcotic peripherally acting antitussive drug, was submitted to toxicological evaluation. The oral (gavage) and intraperitoneal routes in mice and rats and the oral route in rabbits produce very low acute toxicity. Administered by oral route, moguisteine proved to be well tolerated for 26 consecutive weeks and did not induce any general or local effect at up to the respective doses of 240 and 60 mg/kg/day for rats and dogs. In oral (dietary) carcinogenicity studies, moguisteine did not exhibit any carcinogenic effect in mice and rats treated for 87 and 104 weeks, respectively, at up to the dose of 600 mg/kg/day. These results are supported by the absence, both in vitro and in vivo, of mutagenic potential. Considering the overall results of the toxicological studies, it can be affirmed that moguisteine enjoys reliable tolerability, as also shown by a wide safety margin calculated on the basis of the animal and human exposures.
    No preview · Article · Dec 1994 · Arzneimittel-Forschung
  • P Montaguti · E Melloni · E Cavalletti
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    ABSTRACT: Acute intravenous toxicity of some solvents, i.e. dimethyl sulfoxide (DMSO), polyethylene glycol 400 (PEG 400), dimethylformamide (DMF), absolute ethanol (EtOH) and benzyl alcohol (BeOH), was determined in three inbred (CD2F1, B6D2F1 and C57BL/6N) mouse strains used in many preclinical tests, mainly in oncology and toxicology. Haemolytic and precipitation potential tests in vitro were performed to assess the blood compatibility of the investigated solvents and its relationship with the observed symptoms. The single tested solvents did not show any major differences in acute toxicity in the three tested strains with the exclusion of DMSO (less toxic in CD2F1) and BeOH and EtOH (less toxic in B6D2F1). The tested dose ranges in the three strains (in ml/kg) were 1.0-5.66 for DMSO, 2.0-8.0 for PEG 400, 1.0-4.0 for DMF, 0.75-4.24 for EtOH, 0.025-0.4 for BeOH. The lowest tested dose was a safe dose and the highest one was the dose causing mortality in no more than half the animals in each group. The in vitro results suggest avoiding the use of BeOH (which also is more toxic than the other solvents in the in vivo test) and DMSO and using PEG400, EtOH and DMF even though the latter induced a body weight decrease in the B6D2F1 mouse strain. As a general conclusion, dilution of these solvents in water is suggested to ameliorate their blood compatibility and the use of doses not higher than the lowest dose tested in this study is recommended.
    No preview · Article · May 1994 · Arzneimittel-Forschung
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    ABSTRACT: Liver fluke infection (Fasciola hepatica) depresses the drug-metabolizing capacity of the hepatic mixed function oxidase (MFO) and glucuronosyltransferase (GT) enzyme systems, throughout a free radicals mediated lipid peroxidation process. Glutathione (GSH, CAS 70-18-8) administered chronically (100 mg/kg i.p. once daily for 40 days) to experimentally infested rats from the onset to the maximal development of the infection (40th day), greatly reduced the damage to membrane lipids of the liver tissue (primary event of the disease), as judged by malonic dialdehyde (MDA) content (decreased by 80%) and diene conjugation absorption (delta E 1% value falls from 1.94 to 0.67). As a consequence, serum glutamate-oxaloacetate (GOT) and glutamate-pyruvate (GPT) transaminases levels, liver GSH and phospholipid (PL) contents, cytochrome P-450, NADPH-cytochrome-P-450 reductase and some typical cytochrome P-450-dependent activities (p-nitroanisole O-demethylase, aniline hydroxylase, as well as UDP-glucuronosyltransferase (GT) activity, all markedly affected in the acute stage of the disease, tend to recover to the control values. The efficacy of GSH in preventing the impairment of the hepatic drug metabolizing capacity was also demonstrated by using as substrate the widely employed flukicidal agent nitroxinil (3-iodo-4-hydroxy-5-nitrobenzonitrile). The in vitro cytochrome P-450-dependent nitroxinil detoxification (reduction to 3-iodo-4-hydroxy-5-aminobenzonitrile), drastically impaired in infested animals (-80%), is markedly restored (3-fold increase) in GSH-treated rats.(ABSTRACT TRUNCATED AT 250 WORDS)
    No preview · Article · May 1993 · Arzneimittel-Forschung
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    L Crippa · E Ferro · E Melloni · P. G. Brambilla · E Cavalletti
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    ABSTRACT: M-mode and two-dimensional echocardiographic measurements were made from the right sternal border of 50 healthy Beagles (25 males and 25 females) approximately 7 months old. The dogs were conscious and standing during the investigation. The following parameters, in systole and diastole, were measured on the echocardiographic images: left ventricular posterior wall thickness (LVWT); intraventricular septum thickness (IST); left ventricular internal dimension (LVID); and circumference (LVC). Fractional shortening (FS) and ejection fraction (EF) were also calculated. Mean, standard deviation, range and coefficient of variation are reported for each echocardiographic parameter and for body weight. Males and females were considered separately and together. Each parameter was analysed statistically to check for differences between the sexes and for correlations with body weight. A statistically significant difference between the sexes was only observed for LVWT in systole and diastole. A linear regression with body weight was obtained only for LVID in systole and in diastole. The results show that morphofunctional cardiac homogeneity is independent of size in dogs of this breed and age.
    Full-text · Article · Aug 1992 · Laboratory Animals
  • Dr R. Ceserani · I. Casciarri · E. Cavalletti · P. Cazzulani
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    ABSTRACT: Nimesulide, a nonsteroidal anti-inflammatory drug (NSAID), was shown to be less ulcerogenic [dose inducing ulceration in 50% of rats (UD50) > 20 mg/kg orally] than indomethacin (UD50 = 1.6mg/kg orally) and, in contrast to indomethacin, to affect prostaglandin E2 (PGE2) [dinoprostone] and thromboxane A2 (TXA2) formation more potently in inflammatory exudate than in the gastric mucosa in rats. After administration for 3 consecutive days, nimesulide in doses of up to 9 mg/kg orally (about 7 times the anti-inflammatory dose in the carrageenan rat paw oedema assay) did not modify renal function parameters or urinary PGE2 concentrations. In contrast, indomethacin caused a significant increase in blood urea and urinary N-acetyl-β-glucosaminidase and proteins at doses of 9 mg/kg orally (about 3 times the anti-inflammatory dose in the carrageenan rat paw oedema assay), and also significant inhibition of urinary PGE2 concentrations at doses of 3 and 9 mg/kg orally. These results, which have been confirmed by clinical data, suggest that nimesulide has good gastric and renal tolerability.
    No preview · Article · Jan 1991 · Drug Investigation

Publication Stats

813 Citations
72.58 Total Impact Points


  • 2004-2005
    • Cell Therapeutics, Inc.
      Seattle, Washington, United States
  • 1992-1998
    • Boehringer Ingelheim Research Italia
      Milano, Lombardy, Italy
  • 1989
    • Università degli Studi di Sassari
      Sassari, Sardinia, Italy
  • 1985
    • Boehringer Laboratories
      Phoenixville, Pennsylvania, United States