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Biomedical subjects

J Ramis

Publications and source records attributed to J Ramis.

29 records · Page 2Linked to original sources
PubMed1988

The effect of fosfosal and acetylsalicylic acid on leukocyte migration and PGE2 concentration in experimentally induced acute inflammation.

The effect of fosfosal, a non-acetylated salicylic acid derivative, on the content of prostaglandin E2 (PGE2) and the migration of polymorphonuclear leukocytes in inflammatory exudates induced by s.c. implantation of 0.5% carrageenan soaked sponges in rats has been determined. Fosfosal, which does not inhibit PG synthesis in vitro, is capable of reducing, in a dose-dependent manner, the PGE2 content of the exudates, with a maximum reduction of 50-60% at a total dose of 100 mg/kg i.p. Acetylsalicylic acid was slightly more potent (68% reduction, 2 x 50 mg/kg i.p.). Six hours after fosfosal administration, salicylic acid, the principal metabolite of fosfosal, accumulated in the exudates at concentrations of about 100 micrograms/ml. These concentrations were sufficient to inhibit PG synthetase activity in vitro. Neither fosfosal nor acetylsalicyclic acid affected polymorphonuclear leukocyte migration at doses which significantly reduced the concentrations of PGE2. Indomethacin, used as reference, reduced leukocyte migration by 28 and 45% at a dose of 1 and 10 mg/kg i.p. respectively. The results indicate that fosfosal, in spite of its lack of effect on PG biosynthesis in vitro, exerts an effect on the inflammatory locus in vivo which may account, at least in part, for its anti-inflammatory activity. Moreover, our results confirm that the inhibition of PG synthesis and leukocyte migration are mediated by different mechanisms.

Animals↗
PubMed1988

Pharmacokinetics of fosfosal after single and multiple oral doses in man.

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.

Administration, Oral↗
PubMed1986

Effect of triflusal and other salicylic acid derivatives on cyclic AMP levels in rat platelets.

The effect of triflusal, acetylsalicylic acid (ASA), and of their principal metabolites 2-hydroxy-4-trifluoromethylbenzoic acid (HTB) and salicylic acid (SA), alone or combined with dypiridamole (DIP) and/or PGE1 on cyclic AMP levels in washed rat platelets (37 degrees C, 4 min), has been determined. DIP at 0.1 mM increased cyclic AMP levels by 25%. The effect of triflusal and HTB was significant at therapeutic concentrations of triflusal (1 mM: 36% increase) and HTB (0.5 mM: 37% increase). The effect of HTB was always greater than that of triflusal. ASA, at 1 mM and 5 mM, alone or combined with PGE1 was without effect. When 1 mM triflusal was combined with 0.1 mM DIP an increased effect was obtained (95%). ASA, at the highest concentration tested (5 mM), did not modify the DIP-induced increase of cyclic AMP levels.

Alprostadil↗
PubMed1978

Iron metabolism in pigeons.

Several haematological parameters such as haemoglobin concentration, haematocrit, erythrocyte number, reticulocyte concentration, plasma iron and total iron binding capacity were determined in 118 urban pigeons of both sexes. No statistically significant sex differences among these parameters were found. In 36 specimens (23 males and 13 females), the plasma iron turnover was determined using 59Fe. The results obtained in this species, expressed per 100 ml-1 blood. day-1 and Kg-1 body weight. day-1, were compared with those of turkeys, ducks and chickens calculated from earlier papers. The highest values versus body weight were observed in pigeons. Organ (liver, spleen, tibia, heart, leg muscle, ribs, sternal keel, gonads and blood) distribution of 59Fe intravenous injection was analyzed during a period from 5 min up to 120 days (19 different times) in groups of 4 pigeons. At the 6 h period, the organs retained the highest dose (20% of total Fe injected), but by the 2nd day period, the radioiron in the blood represented about 98% of the total injected. A fast iron uptake by the circulatory blood was checked and compared with that of other species (domestic fowl, ducks and turkeys). The reticulocyte count in pigeons normally ranged from 4 to 12%, which was consistent with these results. A linear decreasing radioactivity in blood, with an inflexion point on the 40th day was observed. An inverse correspondence between blood and liver was found. Content in other organs decreased uniformly with time, except the heart where the iron content was practically constant during the whole time. Ribs and sternal keel are erythropoietic organs in young pigeons.

Animals↗
PubMedDate not supplied

Pharmacokinetics of triflusal and its main metabolite in rats and dogs.

The methods for determining plasma concentrations of triflusal (2-acetoxy-4-trifluoromethyl benzoic acid) that have been described, do not distinguish between the drug and its main metabolite HTB (2-hydroxy-4-trifluoromethyl benzoic acid). In the present study, we have developed a new analytical technique based on HPLC that enabled us to carry out a pharmacokinetic study of the drug and its metabolite in animals. An intravenous or oral dose of 50 mg/kg was administered to male Sprague-Dawley rats, and 15 mg/kg was administered to beagle dogs. Plasma levels of triflusal and HTB were determined. In rats, triflusal was quickly eliminated from plasma with a biological half-life (t1/2) of 2.7 min and a clearance (Cl) of 73.4 (ml/kg)/min. The elimination of HTB was much slower with a t1/2 of 21.5 h and a Cl of 5.1 (mg/kg)/h. The maximum concentration (Cmax) of triflusal in rats after an oral administration was 8.1 +/- 2.0 micrograms/ml reached between 2.5 and 10 min. The Cmax of HTB was 237.7 micrograms/ml and was achieved at 0.7 h. The bioavailability of triflusal in rats was only 10.6% while the bioavailability of HTB was more than 100% indicating an important first pass effect. In dogs the t1/2 of triflusal was 14.4 +/- 5.9 min and the Cl was 25.1 +/- 4.7 (ml/kg)/min. HTB was also eliminated very slowly with a t1/2 of 71.1 +/- 12.5 h and a Cl of 2.4 +/- 0.3 (ml/kg)/h. The Cmax of triflusal in dogs was 13.3 +/- 2.9 micrograms/ml and was reached after 19.2 +/- 6.1 min (tmax).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMedDate not supplied

Pharmacokinetics of triflusal and its main metabolite HTB in healthy subjects following a single oral dose.

The pharmacokinetic profile of triflusal (2-acetoxy-4-trifluoromethyl benzoic acid) and its main metabolite HTB (2-hydroxy-4-trifluoromethyl benzoic acid) has been studied in 8 healthy subjects (4 males and 4 females), after a single oral dose of 900 mg of triflusal. Plasma concentrations were determined by a sensitive HPLC method. Sampling was performed up to 120 h post medication. Triflusal displays a Cmax of 11.6 +/- 1.7 micrograms/ml and a tmax of 0.88 +/- 0.26 h. The elimination half-life (t1/2) was 0.55 h with a clearance (Cl/F) of 45.5 +/- 11.0 l/h. HTB kinetic parameters were: tmax 4.96 +/- 1.37 h and Cmax 92.7 +/- 17.1 micrograms/ml, with an elimination t1/2 of 34.3 +/- 5.3 and a clearance of 0.18 +/- 0.04 l/h. The results obtained in this study show a rapid absorption of triflusal and an immediate biotransformation into HTB. The long lasting platelet anti-aggregatory effect of triflusal in spite of its short t1/2, could be explained by the irreversible inhibition of platelet cyclo-oxygenase and the sustained levels of HTB, which also possess anti-aggregant properties.

Administration, Oral↗
PubMedDate not supplied

Hematological parameters and iron metabolism in pigeons and chickens with phenylhydrazine-induced anemia.

A single phenylhydrazine injection (1.8 mg/kg body weight in chickens and 2.2 mg/kg body weight in pigeons) was administered intramuscularly to different lots of animals. The modification of hematocrit, hemoglobin, erythrocyte number, reticulocyte concentration, plasma iron, and total iron-binding capacity was monitored versus time. Depression of the hematological parameters in chickens was greatest on the second day (27-40%), and the values returned to normal by day 7. The drop in pigeons was greater (28-51%) and took longer to return to normal (day 22). The highest percentage of reticulocytes was 35-37%. A plasma iron increase was concomitant to cell destruction and decreased later. The plasma iron clearance values showed a double slope line as a result of the presence of reticulocytes. A high correlation existed between iron uptake by red blood cells at 5 min and the reticulocyte concentration. The responses of the two species to the phenylhydrazine were similar, and differences were more quantitative than qualitative. Reticulocytes were present in normal pigeons, which introduces an important variant in iron metabolism in birds.

Anemia↗