Biomedical subjects

C F Lastra

Publications and source records attributed to C F Lastra.

9 recordsLinked to original sources

PubMed2000

A comparative in vitro study of percutaneous penetration of beta-blockers in human skin.

In vitro diffusion experiments with propranolol, oxprenolol, metoprolol and atenolol were carried out using excised human abdominal skin. The main permeation parameters (permeability coefficient, flow and lag time) were calculated and compared as measurement of intrinsic permeability across human skin. A long lag time and a low steady-state flow were found for all drugs assayed. Skin permeability predicted at steady state did not reach therapeutic concentrations, which indicated the need for appropriate chemical penetration enhancers or vehicles to overcome limiting factors. The results, including those of celiprolol and bisoprolol reported previously, correlated with physicochemical properties, especially with lipophilicity, one of the main factors in drug permeability prediction through human skin.

Administration, Cutaneous↗

PubMed1998

Error structure for the HPLC analysis for atenolol, metoprolol and propranolol: a useful weighting method in parameter estimation.

Three reversed-phase high performance liquid chromatography (HPLC) methods with UV detection were developed and fully validated for the quantification of three beta-blockers: atenolol, metoprolol and propranolol. After validation, error structures for the HPLC analysis were established using a convenient and practical procedure. The mean percentage of relative standard deviation (RSD) of the experimental concentrations (C), were less than 4.29% for proportionality and less than 3.68% for precision for any of the drugs, which allowed the quantitation of beta-blockers assayed at concentrations in the range 25-0.78 micrograms.ml-1. The error structures for the HPLC analysis were: SD (micrograms.ml-1) = 5.02 x 10(-2) C for atenolol, SD (micrograms.ml-1) = 4.55 x 10(-2) + 0.63 x 10(-2) C - 7.58 x 10(-6) C3 for metoprolol and SD (micrograms.ml-1) = 2.73 x 10(-2) C - 3.49 x 10(-4) C2 for propranolol. The reciprocal of the square of the SD of the drug concentrations measured within the calibration curve could be used as weighting methods in parameter estimation by non-linear regression.

Adrenergic beta-Antagonists↗

PubMed1998

Comparative study of different weighting methods in non-linear regression analysis: implications in the parametrization of carebastine after intravenous administration in healthy volunteers.

The influence of different weighting methods in non-linear regression analysis was evaluated in the pharmacokinetics of carebastine after a single intravenous dose of 10 mg in 8 healthy volunteers. Plasma concentrations were measured by HPLC using an on-line solid-phase extraction method and automated injection. The analytical method was fully validated and the function of the analytical error subsequently determined. The parametric approach was performed using different weighting methods, including the homoscedastic method (W = 1) and heteroscedastic methods using weights of 1/C, 1/C2, and the inverse of the concentration variance calculated through the analytical error function (1/V), and the results were statistically evaluated according to the normal distribution. Statistically significant differences were observed in the representative parameters of the disposition kinetics of carebastine. The use of a multiple comparison test for statistical analysis of all differences among group means indicated that differences were generated between the homoscedastic method (W = 1) and the heteroscedastic methods (1/C, 1/C2, and 1/V). The results obtained in the present study confirmed the utility of the analytical error function as a weighting method in non-linear regression analysis and reinforced the importance of the correct choice of weights to avoid the estimation of imprecise or erroneous pharmacokinetic parameters.

Adult↗

PubMed1997

Pentoxifylline, ciprofloxacin and prednisone failed to prevent transplant-related toxicities in bone marrow transplant recipients and were associated with an increased incidence of infectious complications.

TNF-alpha (Tumor necrosis factor-alpha) is involved in many immunological and inflammatory processes, and might be expected to play an important role in the development of BMT-related complications. Triple therapy (pentoxifylline, ciprofloxacin and prednisone) with known anti-TNF activity was tested in 37 patients undergoing a hematopoietic progenitor transplant (HPT). A control group of 16 patients with similar characteristics was selected among consecutive patients receiving a HTP in a neighboring center who did not receive anti-TNF prophylaxis. Major transplant-related complications were registered (VOD, acute GVHD, infectious episodes, renal failure and mucositis) and survival status. TNF plasma concentrations were determined by ELISA, and pentoxifylline plasma concentrations were determined by HPLC. Among patients treated with pentoxifylline (PTX), ciprofloxacin and steroids, no difference in the mean survival time was observed compared with the control group. The incidence of procedure-related death up to day +35 was 11% in the study group and 6% in the control group. In spite of a tendency to a lower incidence of mucositis there was a higher incidence of infections (positive blood cultures) in the study group (49%) than in the control group (16.7%) (P = 0.16). This difference achieved statistical significance in patients receiving an allogeneic HPT (P = 0.05). It is likely that the use of steroids in the early period after transplant increases infectious episodes and makes control of GVHD difficult. The combined administration of steroids with pentoxifylline and ciprofloxacin has not proved beneficial in preventing mucositis, renal failure, VOD or GVHD, or in improving patient survival.

Adolescent↗

PubMed1996

Determination of analytical error function for beta-blockers as a possible weighting method for the estimation of the regression parameters.

Three analytical methods have been developed and validated for the quantification of beta-blockers (celiprolol, bisoprolol and oxprenolol) using high performance liquid chromatography (HPLC) with UV detection. The methods were determined to be linear, precise and accurate (RSDs were lower than 5%), which allowed the quantitation of beta-blockers assayed at concentrations in the range 25-0.78 micrograms ml-1. After validation of reversed-phase HPLC methods, their analytical error functions were established by a rapid, simple and economical procedure. The discrimination of the best function for each active principle was performed by an appropriate polynomial statistical analysis, yielding SD (microgram ml-1) = 0.0295 + 0.0124C - 3.88 x 10(-4)C2 for celiprolol, 0.0199 + 0.011C - 1.27 x 10(-5)C3 for bisoprolol; and 0.0183 + 0.0089C - 9.68 x 10(-6)C3 for oxprenolol. These analytical error functions are an alternative to the weighting methods used in parameter estimation of beta-blockers.

Adrenergic beta-Antagonists↗

PubMed1996

Parametrization by nonlinear regression analysis of the active acid metabolite of ebastine using different weighting methods.

The study of the analytical error function has been applied to evaluate the pharmacokinetics of ebastine active acid metabolite after a single oral dose of 10 mg of metabolite in 6 healthy volunteers. Plasma concentrations were measured using an automated solid phase extraction method. The analytical method was fully validated and the function of the analytical error subsequently determined. The parametric approach was performed by nonlinear regression analysis comparing the results obtained after the application of different weighted least square methods including the homoscedastic method (W = 1) and heteroscedastic methods using weights of 1/C, 1/C2 and the inverse of the concentration variance calculated through the function of the analytical error. The results obtained in the study showed no influence of the different weighting methods used on the estimation of the pharmacokinetic parameters of ebastine acid metabolite.

Administration, Oral↗

PubMed1991

Open-loop feedback control of serum bentazepam concentrations and Bayesian estimation in multiple dosage regimens in patients.

The time course of serum levels of bentazepam was studied in 10 patients receiving anxiolytic agent orally at a dose of 25 mg on multiple dosage regimens with dosage intervals of 8 and 12 h. Using the methods of "open-loop feedback control", no linear regression programs and Bayesian estimation, it was possible to establish the best estimates of the pharmacokinetic parameters corresponding to the single-compartment model for each patient from all their data relating to the serum levels obtained after the first dose and after multiple dosing with different regimens. The application of the Kruskal Wallis test showed that there were only statistical differences for the absorption constant, determined with and without Bayesian estimation. However, no statistically significant differences were found on comparing the experimentally obtained serum levels with the corresponding theoretical values calculated independently for each patient from the parameters established with and without Bayesian estimation. As population pharmacokinetic parameters of bentazepam, the following were established: Ka = 2.330 +/- 0.665 l/h; Vd = 1.209 +/- 0.546 l/Kg and Ke = 0.160 +/- 0.118 l/h, corresponding to a mean value for the elimination half-life of 4.33 h.

Administration, Oral↗

PubMed1991

Adaptive and bayesian control of digoxin in geriatric patients.

The study was carried out in a total of 22 patients classified in two groups: Group "A" (n = 12) was constituted by geriatric patients with cardiac failure diagnostic and with digoxin treatment previously to start our study. Group "B" (n = 10) was also constituted by geriatric patients, but with arteriosclerosis diagnostic and without prior digoxin treatment. Doses of 0.25 mg of digoxin was administered by oral route in a multiple dosage regimen with dosification at times of 0, 24, 48, 72 and 96 h. Samples of blood were obtained at 0, 0.5, 1.75, 7, 24, 49.75, 72 and 168 h after the first administration. The classics one and two-open kinetic model were considered. The elimination constant (Ke) was estimated in function of creatinine clearance (Clcr) according to the following expression: Ke = Kslope * Clcr. The mean value of kinetic parameters established were: For one-compartment kinetic model: Ka = 15.2 and 15.7 h-1, Vd = 5.4 and 4.5 l/Kg and Kslope 0.0006 and 0.0001 min/ml * h for groups "A" and "B", respectively. For two-compartment kinetic model: Ka = 11.5 and 3.6 h-1, K12 = 0.7 and 0.8 h-1, k21 = 0.2 and 0.2 h-1, Vc = 2.7 and 1.9 l/Kg and Kslope 0.0002 and 0.0002 min/ml * h for groups "A" and "B", respectively.

Adaptation, Physiological↗

PubMed1984

Disposition of phosphomycin in patients with pleural effusion.

The pharmacokinetics of phosphomycin were studied in seven patients with pleural effusion of varied etiologies. All patients received a single intravenous bolus of 30 mg of antibiotic per kg. Phosphomycin levels in plasma and pleural fluid were determined simultaneously. Antibiotic levels in plasma followed a two-compartment open kinetic model. In the pleural fluid, maximum concentrations of phosphomycin, 42.63 +/- 16.03 micrograms/ml (mean +/- standard deviation), were reached at 3.69 +/- 1.08 h after administration of the antibiotic. The disappearance constant of the antibiotic from the pleural fluid was significantly smaller (0.16 +/- 0.06 h-1) than the elimination constant determined from the levels of drug in plasma (0.73 +/- 0.26 h-1). Phosphomycin persisted in antibacterial concentrations in the pleural fluid for a considerable period of time. The low accessibility of phosphomycin observed in one of the patients in the study, with a maximum concentration value of 2.16 micrograms of phosphomycin per ml of pleural fluid, could be due to the existence of pachypleuritis in that patient; this was later confirmed in clinical and histological studies done after the research described here.

Aged↗