Biomedical subjects

P Fagiolino

Publications and source records attributed to P Fagiolino.

11 recordsLinked to original sources

PubMed1998

Lipidic matrix of albendazole: an alternative for systemic infections.

Albendazole is a poorly water soluble drug, with low oral bioavailability, used in pharmacological treatment of a systemic disease as hydatid parasitosis. Lipidic matrices of Gelucires (44/14 and 35/02) were developed. After "in vitro" studies, one formulation was chosen for a single dose study in 8 healthy volunteers, with a cross-over and randomised design, taking a commercially available tablet as reference. Drug absorption was followed by albendazole sulphoxide dosage in urine by high pressure liquid chromatography. Neither albendazole nor albendazole sulphoxide were recovered in urine after tablet administration while 0.18% (+/- 0.06) of dose was recovered after lipidic matrix administration in the first 24 hours. Besides ageing control were performed up to 18 months post-elaboration. Lipidic matrix with Gelucire 44/14 was revealed as a promising attempt for oral pharmaceutical form in albendazole systemic treatment.

Administration, Oral↗

PubMed1998

Lipidic matrix of albendazole sulphoxide: is it an alternative for systemic infections?

As albendazole sulphoxide (ABZS) shows better dissolution properties than albendazole (ABZ), a lipidic matrix with this drug was formulated in order to evaluate if its absorption and so systemic infection chemotherapy could be improved. A cross-over, randomised study in 8 healthy volunteers was carried out, after single administration of 1 g of albendazole or albendazole sulphoxide in lipidic matrix of Gelucire 44/14 (ABZLM and ABZSLM). Absorption was followed performing albendazole sulphoxide dosage in urine samples by high pressure liquid chromatography analysis, during 48 hours. Significant differences were found (p = 0.02) between the urinary recoveries (% E48), being 1.74% and 0.19% the percentage of dose recovered when ABZSLM or of ABZLM were respectively administered. In a previous study of our group similar values were obtained of urinary recovery percentages after albendazole sulphoxide powder administered to another group of healthy volunteers. Lipidic matrix does not improve the physicochemical properties of albendazole sulphoxide powder.

Adult↗

PubMed1995

Bioavailability comparison between albendazole and albendazole sulphoxide in rats and man.

Albendazole (ABZ) is a broad spectrum anthelmintic benzimidazole with very low bioavailability, and its activity is due to its main metabolite, Albendazole sulphoxide (ABZS). This work demonstrates the improvement of bioavailability when the ABZS is directly administered, compared with the ABZ administration, both orally given. This observation may be used as an interesting target in the design of new drugs with antihelmintic activity in systemic diseases, using ABZS as a parent drug.

Adult↗

PubMed1994

Influence of the emulsion sign in phenytoin bioavailability.

To study the influence of the emulsion sign in phenytoin bioavailability, two emulsions (w/o and o/w) were prepared. Bioavailability studies were carried out with both emulsions in Wistar male rats. The study was of a randomized two-way cross over design. A radiotracer technique was chosen as analytical procedure, due to the small blood sample collected. 14C-phenytoin was synthesized with a high yield and suitable radiochemical purity. It is concluded, from a biopharmaceutic point of view, that the emulsion sign does not seem to affect the amount of phenytoin absorbed, as it is shown through the comparison of the areas under curve up to 24 h. An emulsion with oil as an external phase is responsible of a longer absorption, taking into account the apparent elimination constant rates.

Animals↗

PubMed1992

Bioavailability study of furosemide prodrugs in rats.

According to the hydrolysis performance "in vitro" and lipophylicity, two Furosemide (F) prodrugs were chosen from a series of acyloxymethylesters of F synthesized previously: P1 (acetyloxymethyl-4-chloro-N-furfuryl-5-sulfamoylanthranilate ) and P4 (pivaloyloxymethyl-4-chloro-N-furfuryl-5-sulfamoylanthranilate+ ++). The bioavailability studies were assayed over two groups of eight male Wistar rats as a randomized two-way crossover and balanced design: group 1) a solution of P1 in propylenglycol/ethyl acetate vs an aqueous solution of F, and group 2) P1 vs. P4 solutions in oleic acid (P1#, P4#). These assays showed a better absorption performance of P1 and P4 than F, while the two prodrugs showed a similar bioavailability. The oleic acid seems to be responsible for the delay in the recovery of 50% of the total amount of F excreted in urine (T50%). When the monitoring is done in plasma after the administration of P1#, P1 was not detected as circulating prodrug. The analytical determinations of F in urine and plasma were done by high performance liquid chromatography (HPLC). From the urinary excretion data, a slope that indicates a slow elimination was found with a half-life of 12 hours approximately.

Animals↗

PubMed1992

Development of absorption furosemide prodrugs: synthesis, in vitro and in vivo evaluation.

Six acyloxymethyl esters of Furosemide were synthesized and the structures were determined by chemical and spectroscopic methods. Lipophilicity parameters were analysed by high performance liquid chromatography (HPLC). Hydrolysis performances in human plasma and intestinal fluids anticipate their properties as absorption prodrugs of Furosemide. A bioavailability study carried out with 8 male Wistar rats with one of the synthesized prodrug (acetyloxymethyl 4-chloro-N-furfuryl-5-sulfamoylanthranilate) showed a greater absorption in relation to Furosemide. The percentages of mean urinary recovery of Furosemide for the prodrug and for the standard solution of the drug were 20.84 and 14.36 respectively. The doses were 10 mg/Kg in Furosemide. The analytical determinations of Furosemide in biological fluids were done by HPLC.

Animals↗

PubMed1991

Linear relationships in systems with non linear kinetics.

The elimination rate of drug from a capacity-limited one-compartment model can be expressed by equation (1): [formula: see text] Traditionally equation (1) was linearized according to equation (2): [formula: see text] Here, an alternative linear relationships between concentration and the area under the curve of C/(Km + c]) is proposed: [formula: see text] By iteration of Km into equation (3) until the statistic of analysis of variance for the regression is maximized, both Km and Vmax can be obtained. Several cases were considered: a) Intravenous bolus (single dose): Km (mg/L), Vmax (mg/L h), Vd (L) and V (mg/h) can be estimated. b) Extravascular administration (single dose): by the method of residuals it is possible to make additional estimations of FD/Vd (mg/L) and Ka (1/h). c) Bioequivalence studies: with parameters obtained at single dose, the simulated levels at steady-state are considered for the bioequivalence assessments. d) Km, Vmax estimation with two (C,t) points (single dose): double iteration (Km values and interpolated fictitious third points) are needed. e) Multiple dose: [formula: see text] If t2-t1 = T (interval of administration) it is possible to calculate operatives Km, Vmax, FD/Vd and to estimate Css (steady-state concentration). C1 and C2 correspond to different intervals. All the areas were calculated by the trapezoidal rule.

Biological Availability↗

PubMed1990

Alternative approach to relative bioavailability and bioequivalence evaluation, with drugs following Michaelis-Menten elimination kinetics.

An alternative approach to bioavailability and bioequivalence assessment is presented. By a modified Wagner-Nelson procedure, the parameters of a monocompartmental model are calculated, after single oral dose administration trials. The usefulness of the procedure described here is that it permits comparison between two different brands of drug in multiple doses, without the need to administer repeated doses. Only one dose is necessary in order to calculate model parameters and infer steady-state levels.

Biological Availability↗

PubMedDate not supplied

Average parameters as a trend to reduce the residual variability in bioequivalence trials.

Bioavailability and bioequivalence evaluations of drug products carried out using the experimental maximum concentration (Cmax) and the experimental time to reach Cmax (Tmax), are not advisable for slow-release formulations and for trials performed with saliva as biologic fluid. When slow-release curves are considered the drug concentration profiles usually show multiple peaks, making it difficult to compute a Cmax,Tmax value. The saliva profile throughout time shows a high variability observed as more than one peak in the saliva concentration versus time curves. In both cases, even if there is a major peak, when the statistical analysis of the data is performed, an important variability in Cmax results in high values in the residual variance of the ANOVA test. Consequently, the power of the bioequivalence test decreases and sometimes it is not possible to conclude on bioequivalence. The average concentration (Cav), the average maximum concentration (Cmax,av) and Cmax,av/Cav x 100 (%Cmax,av) are proposed in this paper as possible parameters in order to evaluate the profile of the concentration-time curves, as they reduce the residual variability in bioequivalence studies.

Analysis of Variance↗

PubMedDate not supplied

Average parameters in bioavailability studies: an application to slow-release amitriptyline formulation.

In order to assess the extent and the rate of absorption in bioavailability studies, area under the curve (AUC), experimental maximum concentration (Cmax) and experimental time to reach Cmax (Tmax), are used. But when slow-release formulations are considered, the drug concentration-time curves usually show multiple peaks, and it is difficult to compute a Cmax and Tmax value. In case a Cmax value is computed, important variability in this parameter results in high values in the residual variance of the ANOVA test. So in order to decrease the high variability, average parameters: average concentration (Cav), average maximum concentration (Cmax,av) and Cmax,av x 100/Cav (%Cmax,av), are proposed. These new parameters were applied in a bioavailability study of slow-release amitriptyline formulation.

Adult↗

PubMedDate not supplied

In vitro approach to study the influence of the cardiac output distribution on drug concentration.

Blood flow is not constant during the day, not only due to cardiac output variation but to the variable blood flow fraction supplied to the organs. To what extent these variations could affect the relative drug concentration between two different tissues, is the purpose of this work. In order to study that, a device was designed which took into account different fluid flows towards two flasks. Connections between flasks and pump are shown in text (figure 1). At the bottom of each flask a non-miscible liquid (dichloromethane: CH2Cl2, 100 mL, places 2 and 3) with the circulating fluid (water, 1350 mL, places 1, A, B) was placed. Malachite Green (MG) was introduced as solute into the system (place 1, 5 mL, 700 mg/L aqueous solution). The pump output was set at 1080 mL/min, serving more fluid (five times) to flask A than to flask B. Samples were drawn from compartments 1, A and B, and from organic compartments, during experiences taking several hours. MG concentrations were colorimetrically measured at 619 nm. Room temperature was between 15-25 degrees C. CH2Cl2 MG concentration ratio([2]/[3]) was similar to fluid flow ratio (sigma/(1-sigma)) all over the experience time. Other experiences changing the stop time, room temperature, CH2Cl2 volumes and places, pump output distribution, led us to different evidences that supported a theoretical model. As a conclusion, the most important feature was that whereas MG concentrations in water (1, A, B) were close, in CH2Cl2 these were very different. So, is drug effect prediction reliable by monitoring free drug concentrations in blood?

Cardiac Output↗