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Biomedical subjects

J Ramis

Publications and source records attributed to J Ramis.

At least 19 recordsLinked to original sources
PubMed1995

The instrumented walker: usage patterns and forces.

Studies documenting the forces that are transmitted through a walker's frame are still scant. The purpose of this study was to evaluate the pattern and magnitude of forces that are transmitted through the frame of a walker during ambulation. A standard aluminum walker was instrumented. Gauges, which were mounted on all four legs, recorded axial, frontal, and sagittally oriented forces. A custom made computerized system registered the forces during 30 seconds of data acquisition. Twelve patients with ambulation dysfunction were tested with this system. Two different usage patterns emerged from the study. One usage pattern was observed in patients who were using the walker as a mean to reduce the amount of weight transmitted through the lower extremity. The second pattern was observed in patients with severe balance problems. These patients used the walker to enhance their balance and stability. The system described allows walker usage pattern analysis. Better understanding of force distribution and usage patterns may lead to improved or new walker design.

Adult↗
PubMed1994

On-line fully automated solid-phase extraction-liquid chromatography analysis of 1,2-dihydro-4-(1,2-dihydro-2-oxo-1-pyridyl)-2,2-dimethyl-1-oxonaphthale ne-6- carbonitrile (UR-8225), a new potassium channel opener, in plasma samples.

A fully automated reversed-phase HPLC method for pharmacokinetic studies was developed for the determination in plasma samples of 1,2-dihydro-4-(1,2-dihydro-2-oxo-1-pyridyl)-2,2-dimethyl-1-oxonaphtha lene-6- carbonitrile (compound I), a new potassium channel opener. On-line solid-phase extraction was performed with disposable C18 cartridges. After clean up, the samples were eluted and transferred onto an RP-18 analytical column, where separation was performed with a mobile phase of acetonitrile-10 mM di-n-butylamine phosphate (28:72, v/v). Ultraviolet absorbance detection was used at 236 nm. The detector response was linear in the range 25-2500 ng/ml, and the lowest limit of quantitation was determined at 2.5 ng/ml. The inter-day variability was < 4% for samples at 1000 ng/ml and < 15% for samples at 10 ng/ml. This method was used for the pharmacokinetic study of compound I in rats at three different dosage levels.

Animals↗
PubMed1993

Species scaling of propafenone disposition and concentration--time relationships among eight mammalian species.

Usually, smaller mammals have higher clearances per unit body mass than do larger mammalian species. When clearance and other pharmacokinetic parameters are correlated with internal physiological processes, species tend to dispose of drugs at a similar pace. The first application of this concept is pharmacokinetic time, expressed with different units: Kallynochron, Apolysichron, Dienetichron, and Syndesichron. The present work describes pharmacokinetic time in these units from data obtained with propafenone in eight animal species: mouse, rat, rabbit, dog, sheep, human, cow, and horse. Additionally, volume of distribution (Vdss = 6.5 B0.94) and clearance (CL = 0.17 B0.86) were correlated to body weight (B). Different units of pharmacokinetic time were evaluated with an Akaike Information Criterion test, and the Syndesichron was the unit that provided the best superimposition for the concentration-time plot for all animal species. It can be inferred that all mammalian species eliminated half of the dose from their bodies in 4759 Syndesichrons.

Adult↗
PubMed1992

Binding of a metabolite of triflusal (2-hydroxy-4-trifluoromethylbenzoic acid) to serum proteins in rat and man.

2-hydroxy-4-trifluoromethylbenzoic acid (HTB) is the main active metabolite of the platelet antiaggregant drug triflusal. Its binding to plasma proteins of rats and healthy volunteers in vitro and in vivo has been studied. Rats were given a single oral dose of 50 mg.kg-1 triflusal and the healthy volunteers received 300 mg as a single oral dose or a multiple dose regimen of 600 mg every 24 h and 300 mg every 8 h, both for 13 days. Protein-free HTB was obtained by ultrafiltration. Unbound and total HTB concentrations were determined by HPLC. HTB was primarily bound to albumin in plasma. The Scatchard plots suggested two types of binding sites for HTB on the albumin molecule. In rats, the binding constants (K = intrinsic affinity constant, n = number of binding sites) were K1 = 1.4 x 10(5) l.mol-1, n1 = 1.23, and K2 = 4.1 x 10(3) l.mol-1 and n2 = 3.77. The mean plasma concentration in rats after oral administration was 185 (37) micrograms.ml-1 (protein-free HTB:2.44 (0.77)%). The binding constants in human plasma were K1 = 4.7 x 10(5) l.mol-1, n1 = 1.93, K2 = 4.3 l.mol-1 and n2 = 4.28. The plasma HTB concentration in man (n = 8) was 35 micrograms.ml-1 (Cmax) after a single oral dose of triflusal 300 mg, 172.96 micrograms.ml-1 (Cmax.ss) during the multiple dosage regimen of 300 mg every 8 h, and 131 micrograms.ml-1 (Cmax.ss) during the multiple oral dose regimen of 600 mg every 24 h. Unbound HTB ranged from 0.27 to 0.43%, depending on dose.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1992

In-vitro protein binding interaction between a metabolite of triflusal, 2-hydroxy-4-trifluoromethylbenzoic acid and other drugs.

2-Hydroxy-4-trifluoromethylbenzoic acid (HTB) is the main active metabolite of triflusal, an antiplatelet drug. The in-vitro binding of HTB to human serum was studied in the presence of different drugs. The results indicate that no statistically significant changes are observed in the HTB binding in the presence of caffeine, theophylline, glisentide, enalapril, cimetidine or warfarin. The free fraction of HTB increases significantly in the presence of the non-steroidal anti-inflammatory drugs studied: diclofenac, ibuprofen, indomethacin, naproxen, piroxicam and salicylic acid. At high concentrations, HTB displaces these anti-inflammatory drugs and also glisentide and warfarin from their protein binding sites.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1992

Percutaneous absorption and skin distribution of [14C]flutrimazole in mini-pigs.

The percutaneous absorption and skin distribution of a skin cream containing 1% 14C-labelled 1-[(fluorophenyl) (4-fluorophenyl) phenylmethyl]-1H-imidazole (flutrimazole, UR-4056, CAS 119006-77-8) was studied in minipigs. The same dose of flutrimazole was administered i.v. and topically (as a cream) on scarified skin according to a crossover protocol. Samples of urine and faeces were taken at various intervals after administration, and radioactivity was measured. The percentage of radioactivity accumulated in urine after topical and intravenous administration were 1.46% and 41.7%, respectively. In faeces, the percentage of radioactivity observed was 6.0% after intravenous administration, and none was detected after topical application. In order to study the distribution and penetration of [14C]flutrimazole, the cream was applied to intact and scarified skin. At various intervals after administration, skin samples were taken. The samples for the autoradiographic studies were cut transversely, and for the measurement of the levels of radioactivity at different skin depths, slices were cut parallel to the cutaneous layers. The results obtained indicate that [14C]flutrimazole penetrates quickly into the different epidermic layers and is retained mainly in the strata spinosum, granulosum and basale. The stratum basale possibly acts as a selective barrier preventing the penetration of the compound into the dermis. The percentage of radioactivity in the stratum corneum is lower than that detected in all the other epidermic layers taken together. The stratum corneum offers low resistance to penetration by the flutrimazole, which very probably crosses the epidermic strata by a transcellular route.

Animals↗
PubMed1992

Pharmacokinetic study of [14C]flutrimazole after oral and intravenous administration in dogs. Comparison with clotrimazole.

This trial involved a comparative study using 6 Beagle dogs on the pharmacokinetics of 14C-labelled 1-[(2-fluorophenyl)(4-fluorophenyl)phenylmethyl]-1H-imidazole (flutrimazole, CAS 119006-77-8) and [14C]clotrimazole labelled in the imidazole ring. On the basis of a cross-over trial, each animal received a dose of 5 mg/kg (approx. 100 microCi) [14C]flutrimazole and [14C]clotrimazole, both intravenously and orally. The levels in plasma, urine and faeces of the total radioactivity, unchanged drug and the [14C]imidazole formed by metabolization of the unchanged drug were determined. Flutrimazole presented a biological half-life (t1/2) of 14.4 +/- 3.8 h and a clearance (Cl) of 6.7 +/- 0.8 l/h, while the values for clotrimazole were very different: t1/2 4.6 +/- 0.8 h and Cl: 13.6 +/- 1.0 l/h. After oral administration a fraction of absorbed dose (f) of 78 +/- 21% and bioavailability of 8.9 +/- 6.1% were calculated for flutrimazole. For clotrimazole, these were: 52 +/- 10% and 4.9 +/- 1.9%, respectively. Both drugs showed a significant first-pass effect, with 90% of the absorbed dose being metabolized before reaching the systemic circulation. The total recovery of radioactivity in faeces and urine 5 days after i.v. and oral administration was 58% and 68%, respectively, for [14C]flutrimazole, and 81% and 79% for [14C]clotrimazole. In both cases, most of the radioactivity was recovered in the faeces. The high radioactivity obtained in faeces after i.v. administration of both drugs confirms biliary elimination. For both flutrimazole and clotrimazole, less than 1% of the total recovered in the urine after i.v. administration was recovered as unchanged drug.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1992

Pharmacokinetic profile of [14C]flutrimazole following single topical application in normal and scarified skin of healthy volunteers.

14C-labelled 1-[(2-fluorophenyl)(4-fluorophenyl)phenylmethyl]-1H- imidazole (flutrimazole, UR-4056, CAS 119006-77-8) was administered topically (dermally) in three male volunteers to normal skin and scarified skin, respectively. Blood, urine and faeces were collected and radioassayed by liquid scintillation counting techniques. After topical application to healthy skin area, less than 1% of flutrimazole was absorbed percutaneously from a 1% cream and the amount absorbed was excreted with the urine. Following administration of the drug to scarified skin, the proportions absorbed were very similar to those measured after application to normal skin. About 0.5% of the administered dose is recovered in urine. The absorbed amount of drug leads to very low concentrations in the circulation, lower than a few ng/ml.

Administration, Topical↗
PubMed1990

Pharmacokinetics of triflusal after single and repeated doses in man.

Triflusal pharmacokinetics were evaluated in 8 healthy subjects after a single 300 mg dose and after repeated doses of 300 mg every 8 h and 600 mg every 24 h during 13 days, with the aim of establishing a relationship between plasma levels and dosage patterns. Plasma concentrations of triflusal and its main metabolite, 2-hydroxi-4-trifluoromethylbenzoic acid (HTB), were determined by HPLC. Triflusal (t1/2 = 29-35 min) metabolized rapidly into HTB. Four h after the first or last repeated dose administration, triflusal levels could not be detected. After the administration of 300 mg every 8 h, the parameters obtained for HTB were: Cmax-ss = 178 +/- 42 micrograms/ml, tmax-ss = 1.9 +/- 0.7 h, Cmin-ss = 155.6 +/- 41.2 micrograms/ml, Cavg-ss = 168.0 +/- 41.8 micrograms/ml and a t1/2 of 48 +/- 15 h. The parameters obtained for the dosage of 600 mg every 24 h were: Cmax-ss = 153 +/- 40 micrograms/ml, tmax-ss = 2.7 +/- 0.9 h, and a t1/2 of 50 +/- 16 h. No significant differences were observed between the elimination half-life obtained after the single dose and after the two repeated dose regimens studied. This finding suggests that HTB displays a linear pharmacokinetic behaviour.

Adult↗
PubMed1989

Pharmacokinetics of fosfosal in rats and dogs.

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.

Administration, Oral↗
PubMed1989

Bioavailability study of fosfosal and codeine administered alone or in combination.

Fosfosal (2-phosphonoxybenzoic acid) is a new salicylic acid derivative which is used for treating inflammatory disease as well as in analgesic therapy. On the other hand, codeine together with acetylsalicylic acid is widely used in patients who require analgesic treatment for mild to moderate pain. The present study was carried out in ten healthy subjects to assess the pharmacokinetic profiles of single oral doses of fosfosal (1,200 mg) and codeine (30 mg) when administered alone or in combination. Blood samples were drawn on each study day and salicylic acid and codeine plasma concentrations were determined by HPLC and enzyme immunoassay methods, respectively. Individual pharmacokinetic parameters were calculated according to standard procedures and the magnitude and rate of bioavailability were tested using a 95% confidence internal approach. Results indicated no statistical differences in any of the kinetic parameters studied except for tmax values which were higher for fosfosal combined with codeine (2 +/- 0.39 h) when compared to fosfosal alone (1.55 +/- 0.35 h). Regarding codeine compared in combination with fosfosal, no significant differences were observed in Cmax and AUC values, while tmax showed a higher value for the combination (1.75 +/- 0.6 vs 0.85 +/- 0.32 h). Although statistical differences in the elimination constant rate and MRT were found between both codeine administrations, these cannot be considered significant in clinical terms. The changes in bioavailability rate observed for both drugs when administered together provide support for the use of this combination in a single formulation.

Adult↗
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↗