Effect of aspirin on liver tests in patients with ra or sle and in normal volunteers

Seaman, William E.; Plötz, Paul H.

doi:10.1002/art.1780190205

Cited by 89 publications

(20 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Oral administration of sodium salicylate to rhesus monkeys did not produce a consistent choleresis when the serum salicylate level was less than 1.0 mmol l. Our studies in man were performed after a large loading dose, but the salicylate levels were within the therapeutic range for patients taking salicylates for rheumatoid arthritis (Seaman & Plotz, 1976).…”

Section: Methodsmentioning

confidence: 66%

The action of salicylates on bile flow in man.

Cooper¹,

Williamson²

1983

Brit J Clinical Pharma

View full text Add to dashboard Cite

Following oral administration of 1.5 g of sodium salicylate or acetylsalicylate to five patients with indwelling T‐tubes there was an approximately 50% increase in bile flow. The increase appeared to be in the bile‐acid independent fraction of canalicular flow and was not accompanied by a change in lithogenicity. Neither agent would be of use in the medical treatment of cholesterol gallstones.

show abstract

Section: Methodsmentioning

confidence: 66%

The action of salicylates on bile flow in man.

Cooper¹,

Williamson²

1983

Brit J Clinical Pharma

View full text Add to dashboard Cite

show abstract

“…The mechanism by which frentizole caused hepatotoxicity is unknown. This drug is metabolized rapidly by the liver ( 12), and it is suspected that frentizole induces idiosyncratic hepatitis similar to that experienced by some patients with SLE who take aspirin (13). No other toxic effects were detected in this short-term trial.…”

Section: Discussionmentioning

confidence: 82%

Frentizole Therapy of Active Systemic lupus Erythematosus

Kay

Valentine

Walker

et al. 1980

Arthritis & Rheumatism

View full text Add to dashboard Cite

Frentizole is a benzimidazoleurea that has immunosuppressive properties in mice. Eleven steroid-treated patients with active systemic lupus erythematosus received frentizole (150-350 mg/day) in combination with stable or decreasing doses of prednisone in an open label trial. Nine patients completed at least one 21-to 75-day course of therapy with this drug. Clinical parameters of disease improved in 8 of these 9 patients. Mean DNA binding decreased by 28%, mean CH50 increased by 20%, and mean absolute lymphocyte and T cell counts decreased by 25-2696. Granulocytopenia was not observed. Three patients developed reversible hepatic toxicity. Clinical and serologic improvement was noted in 3 patients who accepted a second W a y course of frentizole therapy. tive to cytotoxic antineoplastic agents which are used to treat selected autoimmune diseases (1). This drug was selected for testing in humans after initial screening showed that it had immunosuppressive properties in mice (24). In the NZB/NZW mouse model of systemic lupus erythematosus (SLE), therapy with frentizole prolonged life and decreased proteinuria (43). Frentizole had a therapeutic index 3 to 7 times greater than cytotoxic antineoplastic drugs and was synergistic with cortisone (43). When frentizole was given to mice in a dose greater than the amount needed to cause immunosuppression, the incidence of infection was not increased (6). In experimental animals, therapy with frentizole was associated with anemia, hepatic toxicity, and thyroid toxicity after large doses were given over an extended period of time (5,7). The effectiveness of this drug as an immunosuppressive agent and its relatively low toxicity in animals prompted us to design a trial to determine if frentizole had immunosuppressive and/or toxic effects in patients with SLE. PATIENTS AND METHODSEleven adult SLE patients were enrolled in the trial (Table 1). Each patient met the five predetermined selection criteria outlined in Table 2. Patients with one or more of the following findings were excluded: central nervous system lupus; lupus pneumonitis; infection; pregnancy or lactation; earlier cytotoxic drug therapy; uncompensated hemolytic anemia; hematocrit less than 26% or hemoglobin less than 9 gm/ 100 ml; platelet count less than 80,000/mm3; serum creatinine greater than 3 mg/100 ml; blood urea nitrogen greater than 40 mg/100 ml; creatinine clearance less than 50 ml/minUte.Three protocols were utilized in this trial. In each protocol, patients were maintained on previous doses of prednisone, and frentizole was added in a single daily dose for a predetermined length of time. Other concomitantly administered

show abstract

“…For example, highdose salicylate is commonly used in rheu matic diseases. It is known that some, but not all, rheumatic diseases are associated with a much higher incidence of salicylate hepatotoxicity (lupus and juvenile rheuma toid arthritis but not adult rheumatoid ar thritis) [Seaman and Plotz, 1976]. This hepa totoxicity can include hyperammonemia and encephalopathy [Ulshen et al, 1978].…”

Section: Discussionmentioning

confidence: 99%

Salicylate Potentiates Valproate-induced Hyperammonemia in the Rat

Uetrecht¹

1987

Pharmacology

View full text Add to dashboard Cite

Valproic acid is known to cause an increase in blood ammonia levels in humans at the usual clinical dose. In most patients, this increase is small and asymptomatic, but in some patients the increase is larger and is associated with encephalopathy. In this study, valproate also caused a small increase in blood ammonia level (from 50 to 83 μmol/l) in Wistar rats. Salicylate potentiated this increase in blood ammonia (>210 μmol/l) when coad-ministered with valproate at a dose of salicylate which did not cause a significant increase when given alone. Other nonsteroidal anti-inflammatory drugs tested (ibuprofen and naproxen) did not potentiate valproate-induced hyperammonemia, and paracetamol actually appeared to decrease ammonia levels. The degree of hyperammonemia was dependent upon diet, and fasting decreased the level of hyperammonemia. In order to determine what component of the diet was responsible for this effect, protein, fat and carbohydrate were given by gavage, individually and also a mixture of the three. Only the mixture was able to increase the degree of hyperammonemia, even though the number of calories in the mixture and in each nutrient given individually was approximately the same. 2,4-Dinitrophenol, which like salicylate uncouples oxidative phosphorylation, potentiated valproate-induced hyperammonemia at a much lower dose than salicylate. Whether salicylate can potentiate hyperammonemia and lead to encephalopathy in some patients and therefore represents one of the risk factors for observed cases of valproate toxicity remains to be determined. Potentiation of hyperammonemia by salicylates is also consistent with the apparent association between salicylates and Reye’s syndrome which is also characterized by hyperammonemia.

show abstract

Effect of aspirin on liver tests in patients with ra or sle and in normal volunteers

Cited by 89 publications

References 21 publications

The action of salicylates on bile flow in man.

The action of salicylates on bile flow in man.

Frentizole Therapy of Active Systemic lupus Erythematosus

Salicylate Potentiates Valproate-induced Hyperammonemia in the Rat

Contact Info

Product

Resources

About