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Biomedical subjects

E L Mariño

Publications and source records attributed to E L Mariño.

At least 19 recordsLinked to original sources
PubMed2001

Pharmacokinetics of amoxycillin in normal horses and horses with experimental arthritis.

The serum and synovial pharmacokinetics of amoxycillin (AMX) were studied after i.v. administration at a dosage of 40 mg/kg to normal horses and horses with induced aseptic carpal arthritis. The best estimates of serum and synovial pharmacokinetic parameters were calculated by mono or bivariable non-linear regression analysis. A biexponential equation was used to describe the concentration vs. time profiles in both normal and arthritic horses. There were no serum kinetic differences between normal and arthritic horses. There were, however, major synovial kinetic changes between these groups. The rate of penetration from serum to synovial fluid was larger in arthritic animals, indicating better penetration in this case. On the other hand, the rate of disappearance from synovial fluid was larger in normal horses, indicating more persistence of the drug in the diseased joint. Synovial AMX availability increased from 21% in normal horses to 79% in arthritic horses. These findings support the use of AMX for the treatment of infectious synovial joint disease produced by susceptible organisms in horses.

Amoxicillin↗
PubMed2001

Pharmacokinetics of ricobendazole in calves.

The pharmacokinetics of ricobendazole (RBZ) and its major metabolite albendazole sulphone (ABZSO2) were studied in six calves, after administration of RBZ (7.5 mg/kg), using a 10% experimental solution by the intravenous (i.v.) route, a 10% commercial solution by the subcutaneous (s.c.) route, and a 10% experimental suspension by the intraruminal (i.r.) route. Blood samples were drawn during a 60-h period. Plasma drug and metabolite concentrations were determined by HPLC. The pharmacokinetic evaluation in each case was prepared by weighted least-squares nonlinear regression analysis. Ricobendazole i.v. data were best fitted by a two-compartment model. The best pharmacokinetic exponents and coefficients were estimated, and the pharmacokinetic variables for RBZ and ABZSO2 were calculated from them. Similar patterns of plasma disposition were found for RBZ after i.r. and s.c. administration, suggesting delayed release from the s.c. site resembling the slow release of the drug from the rumen.

Albendazole↗
PubMed2000

Two reproducible and sensitive liquid chromatographic methods to quantify atenolol and propranolol in human plasma and determination of their associated analytical error functions.

Two liquid chromatography (LC) methods with fluorimetric detection have been developed to measure atenolol and propranolol in human plasma. The same 5 microm Nucleosil RP-18 column, extraction procedure and mobile phase (containing acetonitrile, water, triethylamine and phosphoric acid, pH 3) were used. The linearity ranges were 25-800 ng/ml for atenolol and 3.13-100 ng/ml for propranolol. The coefficients of variation for validation assays were lower than 15% at the concentration assayed. The functions of the analytical error were linear: SD (ng/ml)=7.698+0.037C for atenolol and SD (ng/ml)=0.126+0.036C for propranolol.

Adrenergic beta-Antagonists↗
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

Determination of celiprolol and oxprenolol in human plasma by high-performance liquid chromatography and the analytical error function.

Two reversed-phase HPLC methods with UV detection to quantify celiprolol and oxprenolol in human plasma are described. The analytical methods for the determination of both drugs used the same reversed-phase HPLC column, mobile phase and extraction procedure. Linearity was obtained in the ranges 15.63-1000 and 25-800 ng/ml for celiprolol and oxprenolol, respectively. Intra-day and inter-day variation was lower than 14%. After validation of the methods, analytical error functions were established as S.D. (ng/ml)=3.096+0.041C for celiprolol and S.D. (ng/ml)=8.906+8.075x10(-8)C3 for oxprenolol.

Adrenergic beta-Antagonists↗
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

The effects of the method of calculation on the evaluation of the pharmacokinetic parameters of oxytetracycline after intravenous administration to calves.

The aim of this study was to assess the differences in the values of the pharmacokinetic parameters attributable to the use of either linear or nonlinear regression analysis and to find the effect of weighting schemes on these differences. Six calves received 20 mg/kg oxytetracycline i.v. Blood samples were drawn during 72 h. The assay of the drug was performed microbiologically. A bicompartmental pharmacokinetic model was used, kinetic analysis being carried out by linear regression (LR) and by weighted least-squares nonlinear regression (WLSNLR). Statistical analysis included a test for normality, the Kruskall-Wallis test and ANOVA with log transformation. The A0, alpha and B0 did not show any statistically significant differences attributable to the mathematical method used. On the other hand, the statistically significant differences in the beta values found using the Kruskall-Wallis test and ANOVA with log transformation could be attributed to the different methods employed. ANOVA with log transformation determined statistically significant differences between the parameters obtained by linear analysis and those obtained by WLSNLR when the weighting (w) was 1. When weights were 1/x, 1/x2 or 1/square root of x, no statistically significant differences were found. The optimal weighting scheme was w = 1/x2 because of a more homogeneous scatter and random distribution of residuals about the abcissa axis in a plot of weighted residuals in the ordinate versus time in the abcissa. It was concluded that the use of these different procedures can give major variations in the apparent value of beta, the most important pharmacokinetic parameter. The correct selection of the weighting procedure is therefore fundamental in obtaining the best estimate of this pharmacokinetic parameter in WLSNLR.

Animals↗
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↗
PubMed1994

Stability of an oral midazolam solution for premedication in paediatric patients.

The objectives of this study were to assess the stability of a 1 mg/ml oral midazolam solution elaborated by our Hospital Pharmacy Service, and to confirm its clinical effect in presurgical paediatric patients. The solution's stability was tested by determining its pH and its UV-visible absorption spectrum at room temperature for up to 60 days. A high performance liquid chromatography method was used to confirm it. There was no significant change in pH value of either the test or a control solution. No loss of midazolam could be detected during the test. The Anaesthesiology Service assessed the sedation quality (very good, good, bad) and the venous puncture response, 20 minutes after the administration of 0.3 mg/kg of an oral midazolam solution. Twenty children were examined (age: 4-7 years). In addition, the haemodynamic and ventilatory functions were evaluated.

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↗
PubMed1990

A discriminatory study of a pharmacokinetic model for intramuscular gentamicin in sheep.

The resulting serum concentrations were measured in six ewes after intramuscular administration of 10 mg/kg of gentamicin. The model providing the best fit for the experimental data was determined both by linear regression analysis between the experimental and theoretical values and by means of the Minimum Akaike Information Criterion Estimation (MAICE) test. Linear regression analysis showed certain differences favouring the monocompartmental model although the advantage was not conclusive. The MAICE test, however, permitted a clear discrimination in favour of the same model. When linear regression analysis is not conclusive, the MAICE test represents a good alternative.

Animals↗
PubMed1988

Discrimination of kinetic models in heteroscedastic parametric estimation of bentazepam following multiple dosing.

The aim of the present study was to attempt to discriminate between single- and two-compartment kinetic models used for calculating the pharmacokinetic parameters of bentazepam when the plasma concentrations of different administrations are used as initial data during multiple dosage regimes. Determination of the best estimated pharmacokinetic parameters was performed using non-linear regression analysis, weighting the data as a function of the error of the analytical technique. Bentazepam was administered at a dose of 25 mg orally at intervals of 8, 12 or 24 h to a total of 9 patients. The mean values of the parameters established for the single-compartment model were Ka = 2.024 h-1; Vd = 2.198 l/kg and Ke = 0.130 h-1. For the two-compartment model these values were: Ka = 2.134 h-1, Vc = 2.049 l/kg, K10 = 0.154 h-1, K12 = 0.042 h-1 and K21 = 0.103 h-1. By application of the MAICE test mean AIC values of 41.62 and 42.52 were obtained for the single- and two-compartment models, respectively. The most suitable kinetic model was determined for each patient according to the predictive nature of the individual parameters of the two kinetic models and by analysis of the residuals of the non-linear regressions of the parametric estimation.

Azepines↗
PubMed1987

Simulation of plasma bentazepam levels in multiple dosage regimens from parameters established by non-linear regression and bayesian estimation.

In the present study, a simulation was made of the time-course of the plasma levels of bentazepam, administered orally at a dose of 25 mg with dosage intervals of 8, 12 and 24 h over 5 days of treatment. The pharmacokinetic parameters corresponding to a single-compartment model were calculated in a previous study with 10 patients who received the drug in a multiple dosage regimen, using all the data relating to plasma levels even though they corresponded to different administrations, by non-linear regression employing programs based on homoscedastic, heteroscedastic and bayesian estimation methods. The mean values of the kinetic parameters obtained previously and used in the present study were as follows: for the absorption constant, mean values of 2.33, 2.18 and 2.75 h-1 were used; for the elimination constant, the values used were 0.10, 0.09 and 0.22 h-1 and for the apparent distribution volume, the values used were 1.89, 2.89 and 0.80 l/kg, with each of the above-mentioned calculation programs, respectively. The highest value for the maximum concentration at steady state proved to be 313.2 ng/ml for a dosage interval of 8 h according to the parameters established with the program using homoscedastic estimation. In the same case (homoscedastic estimation) the highest value of the minimum at steady state was 168.7 ng/ml. By contrast, the lowest value of the maximum value at steady state--129.3 ng/ml--was obtained with a dosage interval of 24 h using the parameters of the heteroscedastic estimation method, while the lowest value of the corresponding minimum was also observed for an interval of 24 h but using the parameters of the bayesian estimation; this was 2.8 ng/ml.

Adult↗
PubMed1987

Phosphomycin levels in serum and interstitial tissue fluid in a multiple dosage regimen in rabbits.

The evolution of phosphomycin (Fosfocina), levels in serum and experimentally induced interstitial tissue fluid and the access of the drug to different organs were studied in rabbits after the administration of a single dose of 60 mg/kg and during a multiple dosage regimen of 60 mg/kg/6 h over three days. Following the administration of a single dose a Cmax value of phosphomycin in interstitial tissue fluid of 80.4 micrograms/ml was reached at 1.2 h. The elimination half-life of the drug from the systemic circulation after a single dose had a value of 1.6 h, and was not significantly different from the value found for the same parameter in the multiple dosage regimen. The disappearance half-life of phosphomycin from interstitial tissue fluid, with a value of 1.9 h for the single dose schedule, was not significantly different from the value of the disappearance half-life of the drug from interstitial tissue fluid in the multiple dosage regimen. Finally, the results of the present study confirm the linearity of phosphomycin kinetics, at least in the conditions studied, and show that the drug is not accumulated in the organs considered.

Animals↗