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M V Calvo

Publications and source records attributed to M V Calvo.

At least 19 recordsLinked to original sources
PubMed2005

[Cochlear implants in Aragón].

Cochlear implants are, actually, one of the major advances in the treatment for profound deafness. His use is, already, a routine in the daily practice of our specialty. Due to its special aspects, cochlear implants have to be done following a protocol that organizes and coordinates the different aspects of the diagnoses and treatment of profound deafness, in the different administrative and geographical fields. The health system in our country and the smale dimension of our area, has taken us to create and follow a special program in which all the available resources are used. Following this protocol, we have performed 63 cochlear implants, in the last 10 years. We show here the results and complications.

Adolescent↗
PubMed2005

Time-dependent pharmacokinetics of cyclosporine (Neoral) in de novo renal transplant patients.

PURPOSE: A model for the large scale temporal trend in the oral bioavailability of microemulsion cyclosporine (Neoral) (CsA) is established, with dependence on post-(renal) transplantation day (PTD). METHODS: Twenty de novo adult renal transplant recipients were monitored for CsA administered orally q12 h. A model development group (11 patients, 315 blood concentration samples) was screened at 2 h (C(2); n = 92), 3 h (C(3); n = 56) and at predose troughs (C(min); n = 167) over periods of up to 75 days. The final model was tested in nine patients with C(min) (n = 580) monitored across 4-5 years. The doses varied between 100 and 538 mg with an apparent hyperbolic trend in C(2)/dose vs. PTD. A nonlinear mixed effects modelling (NONMEM) approach was used to obtain population and individual patient one-compartment pharmacokinetic (PK) parameters for oral CsA, which carry implicit the bioavailability (F). RESULTS: In the final PK model (PK-f) the F was modelled via a simple function for the temporal (days) trend of the bioavailability after transplantation as, F(f) = 1-alpha * exp(-lambda * PTD) resulting in a 28% reduction in the unexplained intra-individual variability. The population PK-f parameters were, for apparent clearance [mean, 95% confidence interval (interindividual CV%)] Cl/F(f) = 17.0 (13.8-20.2) L/h (27%), apparent central compartment volume of distribution, V/F(f) = 134 L (108-160) (28%), and lambda = 0.037/day (0.005-0.069) (120%). The absorption rate k(a) and the parameter alpha were approximated iteratively as 4/h and 0.62 respectively. The PK-f was structurally superior to the base model in explaining part of the within subject (occasion) variability and predicting the exposure surrogates C(2) and C(3). Also, the PK-f was better than the base model with Bayesian fitting of individual profiles in that group. CONCLUSION: The PTD-dependent relative bioavailability model provides a rational means of steering dose titration of CsA in de novo renal transplantation patients by removing the large scale PK adjustment signal, either through nomograms or as a Bayesian prior.

Adult↗
PubMed2004

Purification and characterization of a pregastric esterase from a hygienized kid rennet paste.

Rennet pastes obtained by maceration of gastric tissues from suckling kids are used traditionally to produce some artisanal cheeses in Spain. Besides milk-clotting function, rennet pastes provide proteolytic activity and lipolytic system, essentially pregastric, necessary in the development of piquant flavor typical of these cheeses. A simple and reproducible procedure allows us to obtain a standardized rennet paste that posses the desired activity and is of good microbiological quality. Concomitantly, a kid pregastric esterase (KPGE) was purified to homogeneity. The purification procedure was based on an aqueous extract of hygienized rennet paste (HRP), which was chromatographed on DEAE-Sepharose Fast Flow then adsorbed on phenyl superose followed by a re-chromatography on the same column. The final enzymatic preparation, where the overall activity recovery was 3%, showed a molecular mass of 53 kDa. The highest activity was determined on p-nitrophenyl butyrate, but marked hydrolysis was also detected on beta-naphthyl caprylate. In contrast, low activity on tributyrin (substrate under emulsion form) was detected, thus confirming the esterase character of purified enzyme.

Animals↗
PubMed1999

Population pharmacokinetics of amikacin in patients with haematological malignancies.

The aim of this study was to analyse the pharmacokinetic behaviour of amikacin in patients with haematological malignancies using a mixed-effect model and sparse data collected during routine clinical care. The patient population comprised 207 haematology patients divided into two groups: one for computing the population model (n = 134) and the other for validation (n = 73). A one-compartment model was used and the following covariates were tested for their influence on clearance and volume of distribution: age, gender, weight, parenteral nutrition, creatinine clearance, stage of antineoplastic treatment (induction, consolidation, intensification), number of weeks postchemotherapy, clinical diagnosis, Eastern Cooperative Oncology Group score, neutropenia, hypoalbuminaemia, concomitant medication (vancomycin and/or amphotericin B), overhydration, and autologous or allogenic bone marrow transplant. The nonlinear mixed-effect model (NONMEM) was used to assess the population pharmacokinetic model of amikacin in these patients. Apart from bodyweight and renal function, acute myeloblastic leukaemia and hypoalbuminaemia proved to be the most important covariates explaining the interindividual variability in amikacin pharmacokinetics in patients with haematological malignancies. The predictive performance of this population model for amikacin serum concentrations seems suitable for clinical purposes.

Adult↗
PubMed1998

Multicriteria decision analysis for determining drug therapy for intermittent claudication.

Drugs of various classes are prescribed for intermittent claudication. However, there is some discrepancy between medical practice and the scientific basis for drug selection. We have developed a quantitative criteria-based decision analysis to evaluate all implications of drug treatment choices for intermittent claudication. Pentoxifylline, buflomedil, naftidrofuryl and ticlopidine were the drugs selected for analysis. The evaluation criteria were 1) therapeutic efficacy, 2) safety, 3) patient acceptance and 4) cost. A review panel of experts determined the relative importance of each criterion by assigning points (or utility values) to each one. The points were 48, 20, 14 and 18, respectively, for criteria 1, 2, 3 and 4. A probability value, or numerical estimate of how well a drug meets a criterion, was assigned to each drug for each of the 4 criteria. The probability value was multiplied by the utility value to determine the score for each drug and criterion. The criteria points for each drug were added for a total score for the drug. The drug with the highest overall score was pentoxifylline, with 69 points out of an ideal score of 100. The rank order for the other drugs was buflomedil, ticlopidine and naftidrofuryl. A sensitive analysis showed that the relative ranking of the drugs remained unchanged over a series of data modifications.

Decision Support Techniques↗
PubMed1996

Cost-effectiveness analysis of serum vancomycin concentration monitoring in patients with hematologic malignancies.

OBJECTIVE: This study evaluates the cost-effectiveness of vancomycin serum concentration monitoring in patients with hematologic malignancies. METHODS: The study was designed as a prospective randomized study. Seventy immunocompromised febrile patients with hematologic malignancies were randomly assigned to either a vancomycin therapeutic drug monitoring group (TDM group; n = 37) or to a control group (n = 33). Intervention in the TDM group involved patient follow-up by a clinical pharmacist to obtain and pharmacokinetically interpret serum vancomycin concentrations for dosage individualization. RESULTS: Evaluation of all patients included global clinical response and nephrotoxicity, as well as the economic costs and effectiveness derived from the vancomycin monitoring program. There were no significant differences between the TDM and control groups in the outcome measures, except for the incidence of nephrotoxicity: the rates of minor nephrotoxicity were 33.3% and 13.5% in the control and TDM groups, respectively. The corresponding figures for moderate nephrotoxicity were 9.1% and 0%. Logistic regression analysis confirmed that TDM independently reduced the incidence of nephrotoxicity in this patient population. On the basis of this reduced nephrotoxicity, a incremental cost of $435 per case of nephrotoxicity prevented was found for vancomycin serum concentration monitoring. CONCLUSIONS: A decreased incidence of nephrotoxicity provides evidence of a real clinical benefit to patient management in patients with hematologic malignancies. The TDM for vancomycin therapy in this high-risk population has been shown to be a cost-effective procedure.

Adult↗
PubMed1996

Influence of pharmacokinetic model on vancomycin peak concentration targets.

The aim of this study was to adapt the vancomycin therapeutic range to the kinetic models usually employed in clinical settings (one- and two-compartment models). Estimates of vancomycin pharmacokinetic parameters were obtained for both models in 22 hematologically malignant patients on vancomycin treatment using two serum concentrations and a bayesian algorithm. From these individually estimated pharmacokinetic parameters, an estimation of the maximum (Cssmax), 2 h postinfusion (Css2), and minimum (Cssmin) steady-state vancomycin serum concentrations for the one- and two-compartment models was made for a fixed 30 mg/kg/day dose. The linear regression equations between the predicted Css2 and Cssmin for the one- and two-compartment models do not differ significantly from the identity line, whereas the corresponding equation for Cssmax points to a 61% underestimation of Cssmax when the one-compartment model is used. From this latter regression equation, it is possible to define 20 mg/L (range of 18-21 mg/L) as a target Cssmax vancomycin serum concentration when a one-compartment model is used to monitor vancomycin therapy. Another practical approach would be to define the target concentration by a desired range at 2 h, which corresponds to a Cssmax value of 30-40 mg/L.

Anti-Bacterial Agents↗
PubMed1996

Pharmacokinetics of amikacin in intensive care unit patients.

OBJECTIVE: To characterize the population pharmacokinetics of amikacin in intensive care unit (ICU) patients and to analyse whether these patients show different kinetic behaviour on the basis of their clinical diagnoses. METHOD: The patient population comprised 104 medical ICU patients on amikacin treatment for several presumed or documented Gram-negative infections. Four study groups were defined according to patients' clinical diagnosis: sepsis group (n = 39), trauma group (n = 20), pneumonia group (n = 21) and 'other diagnosis' group (n = 24). The pharmacokinetic parameters for amikacin in these patients were then compared. RESULTS: The ICU patients were found to have increased values for the amikacin volume of distribution (0.52 +/- 0.21 litres/kg), whereas total amikacin clearance expressed as a linear function of creatinine clearance was Cl (ml/min/kg) = 0.13 +/- 0.86 ClCR, which is not significantly different from other estimations reported in the literature. However, this relationship revealed statistically significant differences among the four groups of ICU patients. Moreover, the septic and trauma patients showed higher (but not statistically significant) values for the amikacin volume of distribution. CONCLUSION: The amikacin pharmacokinetic parameters obtained should allow Bayesian individualization of amikacin doses in patients admitted to medical ICUs, on the basis of their clinical diagnoses.

Adult↗
PubMed1995

Comparative kinetic study of lipases A and B from Candida rugosa in the hydrolysis of lipid p-nitrophenyl esters in mixed micelles with Triton X-100.

(1) Lipases A and B from Candida rugosa catalyzing the hydrolysis of esters in micellar media have been characterized kinetically by studies on substrate specificity, rate equation forms and modeling of enzyme mechanisms. (2) The study on specificity revealed that both lipases are non-specific esterases with similar activity against lipid p-nitrophenyl esters micellized with Triton X-100. The slight difference was that lipase A has its maximum activity centered in the caprylate while that of lipase B is in the laurate. (3) Kinetic studies for both lipases were carried out with p-nitrophenyl laurate under three experimental conditions: (I) the molar fraction of substrate is fixed and the bulk concentration of substrate and Triton X-100 are varied; (II) the bulk concentration of substrate is held constant and the molar fraction of substrate and bulk concentration of Triton X-100 are varied; and (III) the bulk concentration of Triton X-100 is held constant but the bulk concentration of substrate and molar fraction of substrate are varied. (4) In case I, a similar Michaelis-Menten behaviour was observed with both lipases; the curve fitting gave kappcat/Kappm values of 3.0.10(5) and 5.6.10(5) s-1 M-1 for lipases A and B respectively. In case II, for both lipases the relationship between rate and the molar fraction of substrate required a fitting equation of 2:2 degree polynomial quotient. In case III, both lipases showed non-Michaelian behaviour with concave-up curves in the Eadie-Hofstee plot, a minimum degree of 2:2 in substrate concentration being detected for the rate equation. (5) The above results are interpreted in terms of the hypothesis that the mechanism of both lipases must include at least two different inputs for the molecule of substrate which would explain the quadratic terms observed in the rate equation.

Candida↗
PubMed1993

Digoxin pharmacokinetics in patients with high serum digoxin concentrations.

Digitalis intoxication is a frequent iatrogenic effect in patients on treatment with digoxin. In the present study we evaluated the pharmacokinetic behaviour of digoxin and the factors responsible for intoxication by this drug in monitored patients exhibiting clinical signs of overdosing with serum levels > 2 ng/ml. A control group of patients was used as a reference whose population pharmacokinetic parameters obtained by a maximum likelihood method were: Vd = 542.92 +/- 274.53 (litre); Cl = 8.73 +/- 1.55 (litre/h) (mean +/- SD). Statistically significant differences (P < 0.001) were found between the mean Cl values in both groups of patients. The difference between the dose-level ratios established in both populations studied also proved to be significant (P < 0.001). Calculation of the optimum dose for each patient showed that the doses recommended in intoxicated patients should be three times lower than those used in the control population. A good correlation was found between the concentrations observed 24 h after administration and the mean concentrations observed at steady state predicted for both population groups. Multiple regression analysis showed that the variables with the greatest predictive value for clearance in intoxicated patients were age and renal function. The modifications observed in the pharmacokinetic behaviour and in the response to digoxin in this type of patient suggest systematic monitoring using pharmacokinetic and clinical criteria jointly.

Adult↗
PubMed1992

Decision analysis to assess cost-effectiveness of low-osmolality contrast medium for intravenous urography.

Decision analysis was used to compare the cost-effectiveness of a conventional ionic high-osmolality contrast medium with that of a nonionic low-osmolality contrast medium when used for i.v. urography. The patient populations considered in the model were those with a low risk and those with a high risk of contrast medium-associated adverse effects. Mean toxicity rates for the contrast media were obtained from the literature. To estimate the average cost of adverse effects, the probability of a patient in each population developing a mild, moderate, or severe reaction was multiplied by the respective estimated cost for each level of severity, and the products were summed. The incremental cost of the low-osmolality medium per case of adverse effects prevented was calculated by dividing the difference between the average costs of the two media by the difference between the frequencies of toxicity associated with the agents. According to the 1990 cost data used, combined mean drug and toxicity costs were $68 and $13 for the low- and high-osmolality contrast media, respectively, per high-risk patient and $67 and $10 per low-risk patient. The incremental costs of the low-osmolality medium per case of severe adverse effects prevented was $17,974 in the high-risk population and $77,027 in the low-risk population. Sensitivity analysis showed the results to be stable over a range of data used in the model.(ABSTRACT TRUNCATED AT 250 WORDS)

Contrast Media↗
PubMed1990

Analytical evaluation of TDx cyclosporine and metabolites fluorescence polarization immunoassay and comparison with the Cyclo-Trac RIA kit.

The fluorescence polarization immunoassay (FPIA) developed by Abbott Laboratories (TDx system) for the determination of cyclosporine in plasma was evaluated using whole blood as the analytical sample. The coefficients of variation for the within-run and between-run precision ranged from 3.7 to 5.7% and from 5.5 to 7.3%, respectively, for cyclosporine controls ranging in concentration from 200 to 1500 ng/ml. The detection limit was seen to be 26 ng/ml. We used specimens from renal transplant patients who received cyclosporine to compare the TDx assay with the RIA method (Incstar Cyclo-Trac). There was a good correlation between FPIA and RA results (r = 0.91; TDx = 1.29 RIA + 39.13; n = 88). It was concluded that the FPIA is an acceptable and rapid method for patient cyclosporine analysis in whole blood samples. In therapeutic drug monitoring this method offers advantages over the RIA procedure.

Cyclosporins↗
PubMed1990

Decision analysis applied to selection of histamine H2-receptor antagonists for the formulary.

The use of decision analysis in selecting a histamine H2-receptor antagonist for the formulary at a hospital in Spain is described. Cimetidine, ranitidine, and famotidine were identified as the possible alternatives. The evaluation criteria established were therapeutic efficacy, adverse effects, drug interactions, years of clinical use, dosage interval, cost, and dosage forms. The relative importance of the criteria was determined by assigning utility values to each. Probability values were assigned to estimate how well each drug met each criterion. By multiplying the utility and probability values for each criterion and summing the scores, a total score was calculated for each drug. The alternative with the highest total score was ranitidine. A sensitivity analysis showed that the results were stable over a plausible range of probability and utility values. Accordingly, ranitidine was selected for inclusion on the formulary. Decision analysis provided an effective method for selecting which histamine H2-receptor antagonist to include on the hospital's formulary.

Decision Making, Organizational↗
PubMed1990

[Decision analysis in antibiotic therapy].

Decision analysis constitutes a systematic approach for taking decisions in situations of uncertainty. This technique allows one to evaluate all therapeutic options and to quantify the possible results, with a view to selecting therapeutic regimens that have the best cost-effectivity relationship. Cost-benefict and cost-effectiveness studies have become increasingly more interesting in the evaluation of antibiotic therapy. In the present paper a review is offered of all factors that, both in antibiotic prophylaxis and the treatment of established infections, govern the cost-effectivity relationship of one's decisions. A review is also made of the methodology of decision analysis, whose use in antiinfective therapy seems sufficiently clear, specially as an objective criterion in the choice of antibiotics.

Anti-Bacterial Agents↗
PubMed1989

Interaction between digoxin and propafenone.

The pharmacokinetic and pharmacodynamic interactions between digoxin and propafenone were investigated in 10 hospitalized patients with heart disease and cardiac arrhythmias. During steady state (0.25 mg/day) the glycoside was combined with 600 mg of propafenone daily for 1 week. The mean +/- SD serum digoxin concentration (SDC) was 0.97 +/- 0.29 ng/ml before and 1.54 +/- 0.65 ng/ml (p less than 0.003) during propafenone administration. Propafenone induced a mean decrease in 31.1 and 31.7% in total and renal digoxin clearances, respectively. The increase in SDCs was accompanied by a decrease in heart rate (HR) and shortening of QTC (QT interval corrected for HR). In patients receiving digoxin and propafenone simultaneously, the SDCs should be monitored and the digoxin dose reduced if there is evidence of toxicity.

Adult↗
PubMed1989

Population pharmacokinetic study of gentamicin and a Bayesian approach in patients with renal impairment.

A population pharmacokinetic study was conducted on a total of 70 patients receiving gentamicin therapy. The patients included those with normal renal function and those with varying degrees of renal impairment. The parameters studied were the apparent volume of distribution and the plasma clearance of gentamicin. The interindividual variability and the residual variability of those parameters in the different subpopulations were studied according to a statistical model that assumed log normal distribution. Use of the one-way ANOVA test revealed statistically significant differences (P = 0.004) in the population plasma clearance of gentamicin in patients below and above 50 years of age. A linear relationship was established between the plasma clearance of gentamicin and the creatinine clearance in those patients. At the same time, the coefficient of variation of the Clp increased progressively in patients with renal impairment, varying between 28.98% in patients with a ClCR greater than 100 ml/min and 76.53% in patients with a ClCR between 20 and 60 ml/min. The results obtained in the population study were later applied to drug monitoring in 23 patients with varying degrees of renal function and who received gentamicin therapy with different doses. The residual variability of the population allowed us to calculate a weighting factor (FF) between the experimental and the population data using Bayesian fitting. The weighting factor was 0.89 in patients with normal renal function and 0.80 in patients with renal impairment. Statistical comparison of the pharmacokinetic parameters obtained from the populational data, non-linear regression and the Bayesian method using revealed differences in the values for the apparent volume of distribution obtained with the two methods.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗