[How can we optimize therapy with sustained-release theophyllines?].
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Biomedical subjects
Publications and source records attributed to J Torrent.
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One tablet containing 755 mg of lithium tryptophanate (10.8 mEq of lithium) was administered to eight healthy volunteers. The main pharmacokinetic parameters for the group of subjects were estimated. Pharmacokinetic parameters (mean +/- SD) from plasma and saliva were respectively: half life (t1/2) 17 +/- 6 vs. 21.8 +/- 14 h; mean residence time 23.7 +/- 7.4 vs. 24.4 +/- 15.3 h; total clearance 30.6 +/- 9.3 vs. 28.6 +/- 6.2 ml/h/kg; and apparent volume of distribution 0.71 +/- 0.20 vs. 0.84 +/- 0.37 L/kg. Although the mean pharmacokinetic parameters in plasma and saliva were similar, there was no significant correlation between the calculated parameters in the individual subject (p greater than 0.05). The usefulness of monitoring salivary levels of lithium is questionable.
In making a protocol it is necessary that all members of the team who are going to collect information have the same unity of criterion about the different variables that compose it. The drawing up of this document is as much or more necessary than the protocol itself.
A simple way to study a histamine antagonist in man is to observe the effect it has on the magnitude of the skin reaction to intradermal histamine. The aim of the present study was to evaluate the antihistamine activity of single oral doses of 75 mg cinnarizine using 75 mg diphenhydramine as control, both being compared to placebo. The study was performed with two groups of 5 healthy subjects, each group receiving one of the active treatments or placebo randomly under blind conditions. All subjects received intradermal injections on the forearm of a 0.05 ml saline solution containing 5 micrograms of histamine before and at different times after drug intake. The histamine-induced wheal area was measured and, after drug administration, the percent decrease of the wheal area was calculated. Results showed that diphenhydramine produced a significant inhibition of the histamine-induced wheal size at 1.5 h which lasted up to 4 h after drug administration, reaching maximum inhibition at 2.5 h. After cinnarizine treatment no significant decrease of the histamine-induced wheal area was observed at any time.
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.
UV-induced erythema is a well known inflammatory model applied both in animal and human skin to test the activity of topical non-steroidal anti-inflammatory compounds in a great variety of pharmaceutical formulations. The aim of this study was to evaluate the inhibitory efficacy of piroxicam in two different topical formulations (cream 0.5, 1 and 1.5% and gel 1%) as compared to three non-steroidal compounds, benzydamine, etofenamate and indomethacin (cream 5%), on erythema induced after UV-injury on the back of 5 healthy subjects. The results showed that piroxicam in cream formulation, indomethacin cream and etofenamate gel have a similar effect, decreasing the erythema size 7 h after irradiation. However, benzydamine cream and piroxicam gel showed no effect with this method. We may conclude that this model is adequate and precise for selecting the most appropriate galenic dosage form for an active compound in terms of its clinical efficacy when topically administered.
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Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
A pharmacokinetic study of carbimide, an inhibitor of aldehyde dehydrogenase, used as an adjuvant in the aversive therapy of chronic alcoholism, has been carried out in male human volunteers for intravenous and oral administration. Carbimide plasma concentrations were determined by a sensitive and specific high performance liquid chromatographic method. The intravenous doses administered were 0.1, 0.3, 0.6, and 1 mg kg-1 and linear pharmacokinetics were observed for this dose range. Elimination half-life and total plasma clearance values ranged from 42 to 52 min and from 14.4 to 20.5 ml kg-1 min-1, respectively. After oral administration of 1 and 1.5 mg kg-1 of carbimide, elimination half-life values were 75 and 61 min, respectively, being higher than the corresponding value obtained after 0.3 mg kg-1 doses, i.e. 39 min. In all cases, rapid absorption was indicated by tmax values ranging from 10.5 to 15.5 min. Absorption was not complete, the oral bioavailability being 53 per cent and 70 per cent for the 0.3 and 1 mg kg-1 carbimide dose, respectively. The data indicate that there is a first-pass effect for carbimide.
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.
The aim of this study was to evaluate the pharmacokinetic profile after single and multidose oral administration of a new slow-release theophylline formulation and the bioavailability at steady-state during two dosing intervals (5th and 8th day) in 6 healthy subjects. A dose of 6 mg/Kg (capsules) was given for the single and at fixed 12 h intervals during 10 days for the multidose schedule. Theophylline kinetics were best described by a one-compartment open model. After single dose the elimination half-life was 7.22 +/- 2.36 h, the Vd area/F was 0.50 +/- 0.07 l/kg and the total clearance/F was 0.86 +/- 0.24 ml/Kg/min, which was similar to results reported in other studies. Steady-state plasma levels were predictable from the kinetic data and were reached between the 4th and 6th dose, falling within the therapeutic range throughout the dosing interval. The percentage of fluctuation remained constant during both intervals, around 33 and 35% respectively. Bioavailability parameter values for the two intervals showed no differences either in extent or in rate. A circadian rythm was confirmed with the mean morning trough values significantly greater than the corresponding mean evening values. From these results it may be concluded that the formulation studied produces few fluctuations of theophylline levels during the 12 h interval between both administrations, thus permitting a good therapeutic cover in chronic therapy.
The growing concerns about water eutrophication have made it urgent to restrict losses of phosphorus (P) from agricultural soils and to develop methods for predicting such losses. In this work, we used the paradigm of P sorption-desorption curves to confirm the hypothesis that the amount of dissolved reactive phosphorus (DRP) released to a dilute electrolyte tends to be proportional to the concentration of DRP in the soil solution raised to a power that decreases with increasing solution to soil ratio (W). The hypothesis was tested for a group of 12 widely ranging European agricultural soils fertilized with P in excess of crop needs. Phosphorus desorption was studied under near-static and turbulent conditions in laboratory experiments. The concentration of DRP in the 1:1 soil to water extract (P1:1) was used as a proxy for the DRP concentration in the soil solution. The amount of desorbed P was found to be correlated with P1:1 raised to a power that decreased from 0.7 to 0.9 at W=100 to 0.2 to 0.4 at W=10 000. Correlation was not improved by introducing additional variables related to P sorption-desorption properties. Olsen P was found to be of lower predictive value than P1:1. Also, the index of degree of soil saturation with phosphorus (DSSP) based on oxalate extraction failed to predict P desorption. The fact that P1:1 seemingly predicts P desorption accurately for a wide range of soils makes it potentially useful in areas of high soil diversity.