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Biomedical subjects

A S Ridolfo

Publications and source records attributed to A S Ridolfo.

At least 19 recordsLinked to original sources
PubMed1985

Antihyperuricemic properties of amflutizole in gout.

The antihyperuricemic properties of amflutizole were investigated in studies designed to determine its efficacy and mechanisms of action in individuals with gout and hyperuricemia. In a randomized double blind, multiple dose, crossover study of 29 patients, amflutizole caused a significant dose dependent reduction in serum urate concentrations. Mean serum urate concentrations decreased significantly from 9.6 +/- 1.5 mg/dl to 7.2 +/- 1.3 mg/dl with the 500 mg dosage (p less than 0.01). Detailed studies in 5 patients demonstrated evidence for modest xanthine oxidase inhibition. However, the majority of the antihyperuricemic effect was derived from an enhanced renal clearance of uric acid. Although the drug has significant antihyperuricemic properties, these were inadequate to achieve adequate control of the serum urate concentration in hyperuricemia and gout at the doses utilized.

Adult↗
PubMed1982

Benoxaprofen kinetics in renal impairment.

To establish therapeutic guidelines, benoxaprofen kinetics were examined in 26 adult subjects with normal and decreased renal function. Mean peak plasma concentrations after a single 600-mg dose ranged from 58 to 72 mg/l, independent of renal function. Elimination half-life and benoxaprofen plasma clearance correlated with creatinine clearance. Hemodialysis did not remove benoxaprofen from plasma. A dosage nomogram was derived from which a dose one half of the normal maintenance dose was suggested for patients with severe renal failure.

Adult↗
PubMed1982

A double-blind study comparing benoxaprofen, aspirin, and benoxaprofen plus aspirin in patients with rheumatoid arthritis.

Ten patients with rheumatoid arthritis completed a study that consisted of 30-day treatment periods with aspirin, benoxaprofen, and benoxaprofen plus aspirin. There were two-week placebo washouts between each treatment. The patients were evaluated biweekly for 15 variables. Each variable was compared for each period; a pooled index was calculated on three combinations of variables. The benoxaprofen-plus-aspirin combination was significantly better than aspirin and better than benoxaprofen alone. This study indicates that combining nonsteroidal anti-inflammatory drugs which inhibit different sites of the inflammatory response (i.e., benoxaprofen, an inhibitor of the directional migration of monocytes, with aspirin, a potent inhibitor of prostaglandin synthesis) may be advantageous in treating patients with rheumatoid arthritis.

Adult↗
PubMed1982

The phototoxic effects of benoxaprofen and their management and prevention.

During clinical trials with benoxaprofen, some patients noted burning and stinging in the skin when exposed to light and some developed onycholysis. A four-part prospective study was undertaken. During the first part of the study it was demonstrated that (1) benoxaprofen is associated with a hypersensitivity to long wave-length ultraviolet light (UVA). During the remaining three parts of the study, patients were exposed to very high doses of UVA light in order to try to induce a photosensitivity response. These studies demonstrated that (2) the symptoms of burning and stinging in the skin and signs of erythema and induration after very high-dose UVA exposure (30 Joule) may be prevented by the prophylactic application of a factor 15 sunscreen; (3) exposure to sunlight is required for the development of onycholysis in patients on benoxaprofen; and (4) the development of onycholysis was prevented by the regular use of a nail polish containing sunscreen. A commercially available, colored, opaque nail polish also would be expected to provide protection from onycholysis.

Anti-Inflammatory Agents↗
PubMed1982

Clinical pharmacology of benoxaprofen.

Eating does not modify benoxaprofen blood concentrations. Combining benoxaprofen with tolbutamide does not significantly change plasma glucose, insulin, or tolbutamide concentrations. Probenecid, by blocking renal tubular secretion of benoxaprofen, increases the benoxaprofen half-life and decreases its renal clearance and urinary excretion. Excretion rate is halved in patients with severe renal impairment. Hemodialysis inefficiently lowers benoxaprofen plasma concentrations. Neither glomerular nor renal tubular function is affected by benoxaprofen, even after five years of therapy. The incidence in urine of microscopic spheroids (benoxaprofen glucuronide complexes) is related to urinary drug concentration and osmolality; increasing the fluid intake decreases incidence.

Adult↗
PubMed1980

Effects of benoxaprofen and indomethacin on platelet function and biochemistry.

Benoxaprofen did not impair platelet function or platelet prostaglandin synthesis in vivo or in vitro in contrast to indomethacin, a known prostaglandin synthesis inhibitor. Platelet cyclic AMP levels were not changed by either drug in vivo or in vitro. The results of routine tests for hemostatic function (template bleeding time and blood clotting assays) were not changed by either drug. A trend towards inhibition of cAMP-dependent protein kinase by benoxaprofen was observed. The significance of this observation, if valid, remains obscure. These studies suggest that benoxaprofen, which does not appreciably suppress hemostatic function, may be used safely in patients with acquired or congenital coagulation defects (e.g. patients receiving oral anticoagulant, hemophiliacs with arthropathy).

Adult↗
PubMed1980

Pharmacokinetic studies of benoxaprofen after therapeutic doses with a review of related pharmacokinetic and metabolic studies.

The pharmacokinetics of benoxaprofen in therapeutic doses of 400 or 600 mg as a solution, capsule or tablet were determined in 44 men after single or multiple doses. The plasma levels of the drug after oral administration of a solution best fitted a 2-compartment open pharmacokinetic model, whereas the levels after the solid dosage forms more appropriately fitted the simple 1-compartment open model. The plasma elimination half-life of the drug, when in solid dosage form, was found to be in the range of 19-26 h, justifying once-a-day dosage. Steady state levels of benoxaprofen were obtained after the 5th dose of a 400 mg capsule every 24 h.

Administration, Oral↗
PubMed1980

Gastrointestinal microbleeding: comparisons between benoxaprofen and other nonsteroidal antiinflammatory agents.

Unlike other nonsteroidal antiinflammatory agents, benoxaprofen has only minor antiprostaglandin synthetase activity. This property may explain the lack of gastric irritation seen in animal studies. To evaluate gastric irritation in man, benoxaprofen was compared with aspirin, naproxen, ibuprofen, sulindac, and indomethacin by measuring fecal blood loss with chromium-51 tagged red blood cells in randomized double-blind crossover and parallel studies. Benoxaprofen produced significantly less blood loss than aspirin, naproxen, or indomethacin, and less blood loss than ibuprofen or sulindac. Benoxaprofen also caused the fewest gastrointestinal complaints.

Anti-Inflammatory Agents↗
PubMed1979

The effect of crystal size on the bioavailability of benoxaprofen: studies utilizing deuterium labeled drug.

A study of the effect of crystal size on the bioavailability of benoxaprofen, 2-[4-chlorophenyl]-alpha-methyl-5-benzoxazoleacetic acid, in man is reported. The technique utilized comparison of either the plasma concentrations or urine levels, resulting from administration of deuterium labeled (2H7) drug in solution coadministered with a test capsule formulation. Drug concentrations were determined by gas chromatography, and the ratio of labeled to unlabeled drug was obtained by gas chromatography mass spectrometry. Measurements following coadministration of labeled and unlabeled drug in solution established the absence of an isotope effect due to the presence of deuterium. The dry formulations consisted of either a 3.17--100 micron fraction (mean = 18.5 microns) or a 32--1000 micron fraction (mean = 610 microns) formulated with starch powder. The results in three subjects indicate an almost complete availability (0.95--0.98) of the small crystals as measured by comparison of either area under the plasma level curves or urine excretion (0.94--0.97) of labeled versus unlabeled drug measured to 168 hours. The larger crystals exhibited a lower availability as shown by plasma levels (0.41--0.46) or urine recovery (0.39--0.43). A higher dose of the large crystal formulation resulted in decreased relative availability with a fourfold dose dropping availability to 0.22 in a single subject.

Adult↗
PubMed1979

Benoxaprofen, a new anti-inflammatory agent: particle-size effect on dissolution rate and oral absorption in humans.

The particle-size effect of benoxaprofen, a new nonsteroidal anti-inflammatory agent, on the in vitro dissolution rate and oral absorption in humans was evaluated. Ten normal subjects participated in a randomized crossover-designed absorption study with two sieved particle-size formulations: one with crystals larger than 60 mesh (mean equivalent spherical diameter = 640 micron) and the other with crystals smaller than 100 mesh (mean equivalent spherical diameter = 67 micron). Plasma drug concentrations and urinary drug excretion were used to determine the relative absorption of the two formulations. The standard USP procedure was used for the dissolution study. Particle size had a dramatic effect on both the in vitro drug dissolution and its oral absorption in humans. In vitro, the smaller crystals dissolved more rapidly and more efficiently than the larger crystals. In vivo, the smaller crystals produced higher plasma concentrations, more rapid peak concentration attainment, and more drug excreted in the urine.

Anti-Inflammatory Agents↗
PubMed1979

Pseudolymphoma of the lung in a patient with systemic lupus erythematosus.

A 47 year old woman with systemic lupus erythematosus was found to have asymptomatic pulmonary nodules. Histologically they represented benign reactive lymphoreticular hyperplasia compatible with the diagnosis of pseudolymphoma. Immunofluorescence and electron microscopy demonstrated immunoreactants and electron-dense deposits in the alveolar and vascular walls, suggesting that an immune complex mechanism may be involved in this case.

Complement C3↗
PubMed1978

Nonsteroidal anti-inflammatory agents in arthritis.

Aspirin remains the agent of first choice, but ibuprofen, fenoprofen, naproxen and tolmetin are useful drugs in rheumatoid arthritis. Ibuprofen and fenoprofen are also approved for use in osteoarthritis. Each shares anti-inflammatory, analgesic and antipyretic properties with aspirin, phenylbutazone and indomethacin. The nonsteroidal anti-inflammatory agents have fewer minor side effects than aspirin and fewer major side effects than indomethacin or phenylbutazone. The patient must understand that drugs are but one part of a comprehensive management program.

Administration, Oral↗
PubMed1977

Gastrointestinal blood loss. Effect of aspirin, fenoprofen, and acetaminophen in rheumatoid arthritis as determined by sequential gastroscopy and radioactive fecal markers.

The feasibility of determining the exact site and amount of drug-induced gastric bleeding was tested. Fourteen patients with rheumatoid arthritis received equivalent therapeutic doses of the antinflammatory drugs aspirin, 4 gm/day, and fenoprofen calcium, 2.4 gm/day, in randomized order for seven days. Acetaminophen was given for 14 days just prior to each of these periods. By fiberoptic gastroscopy, antral ulceration and acute mucosal lesions were found in seven patients following aspirin ingestion, in one taking fenoprofen, and in none taking acetaminophen. Fecal blood loss in four-day stool collections, quantitated by autologous chromium 51-labeled erythrocytes shed into the stool averaged 5.0 ml/day while taking aspirin, 2.2 ml/day while taking fenoprofen calcium, and 0.8 ml/day while taking acetaminophen. The mean blood loss was greater for those in whom gastric lesions developed while taking aspirin than for those in whom lesions did not develop. The short-term risk of erosive gastritis was greater for aspirin than fenoprofen.

Acetaminophen↗
PubMed1977

A quantitative evaluation of rheumatoid arthritic activity with Tc-99m HEDP.

In an attempt to develop a quantitative method of evaluating rheumatoid arthritic activity, Tc-99m HEDP joint uptake values and joint-to-bone ratios were studied in ten adult rheumatoid arthritic patients and 17 nonarthritic patients. A joint-to-bone activity ratio of 1.8 at the fourth hour after injection (RA Index) discriminated clinically active rheumatoid arthritic joints from control joints with 95% accuracy. Serial studies on five patients during drug trial demonstrated a positive correlation between RA Index and the clinical manifestations of rheumatoid arthritic activity. The RA Index may be a useful quantitative parameter for evaluation of rheumatoid arthritic activity following therapy.

Adult↗
PubMed1976

Comparison of benefit-to-risk ratios of aspirin and fenoprofen: controlled multicentre study in rheumatoid arthritis.

The benefit-to-risk ratios of fenoprofen (2.4 gm/day) and aspirin (3.9 gm/day) were compared in a randomized, double-blind, 26-week parallel study involving 216 patients. Criteria for inclusion, exclusion, subjective, and objective evaluations were based on the PMA-FDA Nonsteroidal Anti-Inflammatory Drug Clinical Testing Guidelines. Thirty-four of 109 aspirin-treated patients and 23 of 107 patients on fenoprofen dropped out of the study. Both fenoprofen and aspirin brought about improvement in most efficacy parameters measured, but fenoprofen was superior to aspirin (p less than 0.05) in reduction of swollen joints, grip strength, activity index, and patients' preference of medication. The number and frequency of complaints and the incidence of abnormal SGOT levels, were greater with aspirin than with fenoprofen. The study suggests that fenoprofen has a better benefit-to-risk ratio than aspirin, when given in equally effective doses.

Adolescent↗