salicylates and fosfosal

Topics: Aged; Analgesics; Aspirin; Bone Diseases; Clinical Trials as Topic; Double-Blind Method; Female; Humans; Joint Diseases; Lysine; Middle Aged; Muscular Diseases; Organophosphates; Organophosphorus Compounds; Pain; Placebos; Salicylates; Stomach

Fosfosal or 2-phosphonoxybenzoic acid is a new analgesic drug, whose analgesic activity and side effects have been determined in a double blind clinical study in comparison with placebo. The study has been done with 60 outpatients, of both sexes, which suffered musculoskeletal and arthritic pains. Patients were treated with fosfosal or placebo for eight days. The daily dose of fosfosal was 1 gram three times a day, once every 6-8 hours. The results obtained show that fosfosal has a clear analgesic activity, statistically significant versus placebo in all the parameters that were measured: pain severity, activity impairment and insomnia. The overall evaluation of the group of patients treated with fosfosal showed a marked improvement with a difference statistically significant with respect to the control group treated with placebo (p less than 0.001). The distribution of results in the fosfosal treated group was as follows: poor, 1; regular, 8; good, 10 and excellent, 6. The distribution in the placebo group was as follows: poor, 15; regular, 3; good, 2 and excellent, 0. The marked analgesic activity, the absence of side effects and the excellent gastric tolerance suggest that fosfosal is a promising new analgesic drug useful for the treatment of painful syndromes of several etiologies.

Topics: Adult; Aged; Analgesics; Arthritis; Bone Diseases; Clinical Trials as Topic; Double-Blind Method; Female; Humans; Male; Middle Aged; Muscular Diseases; Organophosphates; Organophosphorus Compounds; Pain; Salicylates

Fosfosal (Disdolen) is a non acetyl derivative of salicylic acid with antiinflammatory and analgesic properties and a greater tolerance than acetylsalicylic acid and lysine acetylsalicylate. In the present work the pharmacokinetics of fosfosal have been studied after oral and intravenous administrations of 100 and 80 mg/kg in rats and dogs, respectively. Plasma concentrations of fosfosal and salicylic acid were determined by an HPLC method. After intravenous administration fosfosal plasma levels decreased rapidly showing a half-life of 2.7 min in rats and 6.7 min in dogs. Fosfosal in plasma is quickly hydrolyzed into salicylic acid producing high concentrations in few minutes after administration. The half-life of salicylic acid was 13.8 and 7.1 h for rats and dogs, respectively. After oral administration only salicylic acid was detected in plasma, indicating that fosfosal, when orally administered, behaves as a prodrug. From the comparison of the AUC for salicylic acid obtained after oral and intravenous administrations it can be deduced that fosfosal it totally absorbed in the two species studied.

Topics: Administration, Oral; Animals; Chromatography, High Pressure Liquid; Dogs; Female; Half-Life; Injections, Intravenous; Organophosphates; Organophosphorus Compounds; Rats; Salicylates; Species Specificity

Fosfosal is a new salicylic acid derivative used in analgesic and anti-inflammatory therapy. In this study, pharmacokinetic evaluation of fosfosal after a single 2,400 mg and three different oral dose schedules (1,200 mg t.i.d., 2,400 mg b.i.d. and 2,400 mg t.i.d.) was carried out, in six healthy male volunteers, to assess which doses provide steady state plasma concentrations within the therapeutic range (150-300 micrograms/ml). Plasma concentrations of both fosfosal and its active metabolite, salicylic acid, were determined by means of an HPLC method. For the 2,400 mg t.i.d., Cmin-ss and Cmax-ss values were 184 micrograms/ml and 276 micrograms/ml, respectively, being significantly higher (p less than 0.02) than with the other regimes and, unlike the latter, falling within the anti-inflammatory therapeutic range. In addition, the 2,400 mg t.i.d. showed a significant prolongation (p less than 0.005) of salicylic acid t1/2, as well as a higher AUC-ss 0-8 h dosing interval compared to the other multidose schedules and to the AUC0-infinity for the single dose. As expected, both facts reflect that the highest daily dose of fosfosal has a nonlinear concentration-dependent elimination rate.

Topics: Administration, Oral; Adult; Anti-Inflammatory Agents, Non-Steroidal; Drug Administration Schedule; Humans; Male; Organophosphates; Organophosphorus Compounds; Salicylates

Topics: Animals; Aspirin; Chemical Phenomena; Chemistry; Organophosphates; Platelet Aggregation; Rats; Salicylates

Topics: 3',5'-Cyclic-AMP Phosphodiesterases; Analgesics; Animals; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Hemolysis; Male; Mice; Organophosphates; Organophosphorus Compounds; Platelet Aggregation; Prostaglandins; Rats; Salicylates; Stomach Ulcer

Acute, subacute and chronic toxicity studies of 2-phosphonoxy benzoic acid (fofosal) were carried out in several animal species. LD50 values in mice and rats were determined at two pH values; an additional toxic effect of acidity was found at the lowest pH tested (pH = 1.0), specially so by i.p. route. Differences in LD5- values between mice and rats of either sex were not significant; however, acute toxicity of male rabbits was higher than that of rats and mice. Long-term toxicity studies revealed a slight growth retardation and a significant mortality at the highest dose tested (500 mg/kg). These studies showed that fosfosal produced no hematological, blood chemical or pathological changes.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Female; Lethal Dose 50; Organ Size; Organophosphates; Organophosphorus Compounds; Rats; Salicylates; Sex Factors; Species Specificity; Time Factors

Topics: Alkaline Phosphatase; Escherichia coli; Hydrogen-Ion Concentration; Kinetics; Organophosphates; Osmolar Concentration; Phosphorylation; Salicylates; Tromethamine