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A Domínguez-Gil

Publications and source records attributed to A Domínguez-Gil.

At least 19 recordsLinked to original sources
PubMed2004

[Pharmacoeconomic analysis of patients with acute exacerbation of chronic bronchitis treated with telithromycin or cefuroxime-axetil].

INTRODUCTION: A pharmacoeconomic analysis was done to compare the efficiency of two treatments in the acute exacerbation of chronic bronchitis: telithromycin and cefuroxime-axetil. METHODS: Restrospective analysis, modeled through a decision tree. The effectiveness of the treatments was estimated through a randomized and double-blind clinical trial in which 800 mg/day (5 days) of telithromycin were compared with 1,000 mg/day (10 days) of cefuroxime-axetil in patients with acute exacerbation of chronic bronchitis (140 and 142 patients, respectively). Resources use was estimated from clinical trial and from Spanish data, and the unit costs through a health costs dabatase. The model was validated by a panel of Spanish clinical experts. RESULTS: Since the clinical trial was designed to demonstrate equivalence, there were no significant differences of effectiveness among both treatments (with a rate of clinical cure of 86.4% and 83.1%, respectively) which means that an analysis of costs minimization was done. In the average case, the average cost of the disease by patient was 174.83 Euros with telithromycin and 194.68 Euros with cefuroxime-axetil (a difference of 19.85 Euros). The results were maintained in the analysis of sensitivity, with favorable differences for telithromycin that ranged between 18.04 Euros and 22.25 Euros. CONCLUSIONS: With telithromycin up to 22 Euros by patient with acute exacerbation of chronic bronchitis could be saved, in comparison with cefuroxime-axetil.

Acute Disease↗
PubMed2003

[Pharmacoeconomic analysis of community-acquired pneumonia treatment with telithromycin or clarithromycin].

A pharmacoeconomic analysis was carried out comparing the efficacy of two treatment options for community-acquired pneumonia (CAP): telithromycin and clarithromycin. It was a retrospective analysis using a decision tree model. The efficacy of the two treatment options was estimated from a randomized, double-blind clinical trial, in which 800 mg/day oral telithromycin for 10 days was compared to 1000 mg/day oral clarithromycin for 10 days in patients with CAP (162 and 156 respectively). The use of resources was estimated based on the clinical trial and Spanish sources, and the unit costs from a Spanish health costs database. Costs were evaluated for the acquisition of antibiotic treatments, change of antibiotic due to therapeutic failure, hospital admissions, adverse reactions to treatment, primary care visits, tests and indirect costs (working days lost). The model was validated by a panel of Spanish clinical experts. As the clinical trial was designed to show equivalence, there were no significant differences in efficacy between the treatment options (clinical cure rate 88.3% and 88.5%, respectively), and a cost minimization analysis was performed. In the base case, the average cost of the disease per patient was 308.29 euros with telithromycin and 331.5 euros with clarithromycin (a difference of 23.21 euros). The results were stable in the susceptibility analysis, with differences favorable to telithromycin ranging between 5.50 and 45.45 euros. Telithromycin results in a cost savings of up to 45.45 euros per CAP patient compared to clarithromycin.

Anti-Bacterial Agents↗
PubMed1999

Population estimation of valproic acid clearance in adult patients using routine clinical pharmacokinetic data.

The aim of the present study was to estimate valproic acid (VPA) clearance values for adult patients with epilepsy, using serum concentrations gathered during their routine clinical care. Retrospective steady state serum concentrations data (n=534) collected from 208 adult patients receiving VPA were studied. Data were analysed according to a one-compartment model using the NONMEM program. The influence of VPA daily dose (Dose), gender, age, total body weight (TBW), and comedication with carbamazepine (CBZ), phenytoin (PHT) and phenobarbital (PB) were investigated. The results of the population pharmacokinetics analysis were validated in a group of 30 epileptic patients. The final regression model for VPA clearance (Cl) was: $¿rm Cl¿left (¿rm L/h ¿right )=0¿rm. 004¿times TBW¿times Dose ¿0.304¿¿rm ¿times 1.363¿,¿rm CBZ¿times 1. 541¿,¿rm PHT¿times 1.397¿,¿rm PB.$ The inter-individual variability in VPA clearance, described by a proportional error model, had a variation coefficient (CV) of 23.4% and the residual variability, described using an additive model, was 11.4 mg/L. These results show that VPA clearance increased linearly with TBW, but increases nonlinearly with increasing VPA daily dose. Concomitant administration of CBZ, PHT and PB led to a significant increase in VPA clearance. The model predictions in the validation group were found to have satisfactory precision and bias. In conclusion, inter-individual variability in VPA clearance can be partly explained by TBW, daily dose and bitherapy with CBZ, DPH or PB. Inclusion of these factors allows this variability to be reduced by 37.23% which may be very useful for clinicians when establishing the initial VPA dosage regimen. However, the magnitude of inter-individual plus residual variabilities, remaining in the final model, render these dosage predictions imprecise and justify the need for VPA serum level monitoring in order to individualize dosage regimens more accurately.

Adolescent↗
PubMed1999

Valproate population pharmacokinetics in children.

OBJECTIVE: A population analysis of the kinetics of valproic acid (VPA) in children with epilepsy was performed in order to characterize the covariates which influence VPA clearance (CL). METHODS: A total of 770 steady-state serum concentration samples was analysed. These were collected during VPA therapy from 255 children, aged 0.1-14 years and weighting 4-74 kg. Age, total body weight (TBW), VPA daily dose, sex and comedication with carbamazepine (CBZ) were considered as covariates. Population analysis was made with NONMEM program, assuming a one-compartment model, fixing the VPA absorption rate, bioavailability and distribution volume at values found in the literature. The results of the population pharmacokinetics analysis were validated in a group of 45 epileptic patients. RESULTS: The final regression model for VPA clearance, that included TBW (kg), daily dose (mg/kg) and CBZ comedication as covariates with a significant influence on this parameter, was as follows: CL (L/h) = 0.012 TBW0.715 DOSE0.306(1.359 CBZ). The coefficient of variation for interpatient variability in CL was 21.4% and the residual variability estimated was 23.9% for a concentration of 65 mg/l. In order to estimate the predictive performance of the selected final model, predictions of the VPA serum concentrations were calculated and compared with VPA measured concentrations in the validation group. This assessment revealed an important improvement in the predictive performance of VPA concentrations in comparison with the basic model that did not include any covariates (root squared mean error: 19.50 vs. 39.73 mg/l). CONCLUSION: A population pharmacokinetic model is proposed to estimate the individual CL for paediatric patients receiving VPA in terms of patient's dose, weight and concomitant CBZ, in order to establish a priori dosage regimens.

Adolescent↗
PubMed1997

Carbamazepine population pharmacokinetics in children: mixed-effect models.

The aim of the authors' study was to investigate the factors affecting carbamazepine (CBZ) clearance (CL) in children with epilepsy. The factors evaluated were total body weight (TBW), age, dose, sex, and phenobarbital (PB) and valproic acid (VA) comedication. A total of 387 steady-state serum concentration samples was analyzed. These were collected during CBZ therapy from 201 children, aged 1-14 years and weighting 9-78 kg. Population CL was calculated by using NONMEM, with a one-compartment model with first-order absorption and elimination. The absorption rate, bioavailability, and volume of distribution were set at values found in the literature. The model found best to describe the data was CL = (0.0122 TBW + 0.0467 Dose) Age0.331 (1.289 PB). The interindividual variability in CL had a variation coefficient (CV) of 11.8%, and the residual error, described by using an additive model, was 1.5 mg/l. The results show that CL increases linearly with TBW and nonlinearly with age; thus older children have a lower CL with respect to TBW than do younger ones. Likewise CL was seen to increase with the increase in the CBZ dose, suggesting a dose-dependent autoinduction of CBZ metabolism. Concomitant PB administration affected CL: however, sex and VA comedication did not affect it significantly. The final regression model for CL, was validated in a different group of 74 children. The standarized prediction error (SPE) was not significantly different from zero (SPE = 0.028), indicating that the model proposed for CL can be used to make accurate dosage recommendations. With these population estimates, CBZ doses that would be suitable for pediatric patients of different ages are proposed.

Adolescent↗
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

Bayesian forecasting in paediatric populations.

Bayesian forecasting offers several important advantages for dosage individualisation in children, although, unlike for adults, its use in this population is much lower. Indeed, currently Bayesian methods are underused in this patient population. The paucity of paediatric population pharmacokinetic parameters, and the unavailability of specific clinical pharmacokinetic software for the whole paediatric population, are the main limitations to the application of Bayesian methods in these patients. When these problems have been overcome, this approach will allow clinicians to achieve therapeutic concentrations more readily, faster and more precisely, thus making the methodology highly attractive in the paediatric setting.

Adolescent↗
PubMed1995

The influence of adrenalin on the pharmacokinetics of interpleurally administered lidocaine in patients with pancreatic neoplasia.

The influence of adrenalin on the pharmacokinetics of lidocaine given interpleurally to 10 patients with pancreatic neoplasia was studied. Five patients received an interpleural dose of lidocaine (200 mg; control group), and 5 patients received an interpleural dose of lidocaine (200 mg) plus adrenalin (1:200,000). Plasma and cerebrospinal fluid (CSF) levels of lidocaine were measured before and at specified times (up to 8 hours) after the dose. The analytical technique was radioimmunoassay; and plasma and CSF data were assessed using noncompartmental analysis. The drug was quickly absorbed into the plasma in the control group (Cmax = 2.76 +/- 0.10 microgram/mL at 0.33 +/- 0.14 hours after administration); whereas drug access to CSF was decreased and occurred slowly (Cmax = 0.32 +/- 0.07 microgram/mL at 1.66 +/- 1.35 hours). The drug was eliminated more quickly from plasma than from CSF, with half-lives of 1.71 +/- 0.43 hours and 3.86 +/- 1.27 hours, respectively. The simultaneous administration of adrenalin delayed absorption (tmax = 0.91 +/- 0.52 hours). The drug elimination half-lives in plasma and CSF of this group increased to 3.22 +/- 1.22 hours and 8.71 +/- 3.28 hours, respectively. The duration of the analgesia, evaluated as the time until the patient needed another dose, increased from 8.2 +/- 1.5 hours in the control group to 9.7 +/- 1.3 hours in the group that received adrenalin. From these results the levels that would be reached on a multiple-dose regimen (D = 200 mg, tau = 8 hours) were predicted.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗
PubMed1994

Interspecies scaling of cimetidine-theophylline pharmacokinetic interaction: interspecies scaling in pharmacokinetic interactions.

The aim of the present study was the use of an interspecies scaling approach to predict drug interactions during preclinical drug disposition studies. Theophylline and cimetidine were selected because of their documented interaction. The literature was searched for pharmacokinetic data of intravenously administered theophylline alone and in the presence of cimetidine in humans, dogs and rats. Further, we determined the theophylline-cimetidine drug interaction in rabbits. Application of allometric equations to the pharmacokinetic parameters and the conversion of chronological time into pharmacokinetic time allowed us to obtain the complex Dedrick plot for theophylline when administered alone or in combination with cimetidine. A superimposable kinetic profile was obtained for the plasma levels of theophylline in all species studied, both with and without cimetidine. From the terminal phase of the curves it is possible to calculate the elimination half-life: 2.69 apolisychrons for theophylline when it is administered alone and 3.86 apolisychrons when it is administered in combination with cimetidine. This 43% increase in t1/2 is similar to the increase in the elimination half-life of theophylline in humans when it is administered after pretreatment with cimetidine. These results show that an interspecies scaling approach may be useful to predict the effect of interactions in humans from the results obtained in preclinical research with new drugs.

Animals↗
PubMed1994

[Follow-up of antitubercular treatment].

Tuberculosis is a first magnitude sanitary problem with several factors that make difficult its eradication, among these are particularly important those derived from the antituberculous therapy: noncompliance and adverse reactions to the drugs used. We have developed a follow-up program for ambulatory patients with antituberculous therapy that includes compliance control and systematical survey or possible adverse reactions. We expose our results after its application to 39 patients with tuberculosis and 24 with tuberculous infection. The compliance level among patients with tuberculous disease was 100% and among those who were receiving chemoprophylaxis 75%, both values much higher than those found in the literature. We detected adverse reactions in 43.6% of the patients with tuberculous treatment and 37.5% of those receiving chemoprophylaxis with isoniazid. Setting up follow-up programs in antituberculous treatments notably helps to improve the compliance and the safety of treatment.

Adolescent↗
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↗
PubMed1993

Plasma protein binding kinetics of valproic acid over a broad dosage range: therapeutic implications.

The aim of the study was to characterize, from the relationship between total and free serum levels of valproic acid obtained over a broad dosage range (10-50 mg/kg), the parameters defining the in-vivo kinetic behaviour of the binding of valproic acid to plasma proteins, their pharmacokinetic and clinical repercussions, and their application to therapeutic drug monitoring (TDM). The study was performed in nine healthy adults (20-35 years) who were given doses of 1000 (group A), 2000 (group B) and 3000 mg (group C) of sodium valproate according to a compensated cross-over design, simultaneously determining the total and free serum levels of valproic acid over a 24-h period. The mean free fraction increases with dose, although this increase is only significant (P < 0.05) for the highest dose (3000 mg). The variation in the free fraction of valproic acid begins to become significant (P < 0.05) at a total drug concentration above 100 mg/l. The mean values of the dissociation constant (K) and binding sites (n) were 460 mumol/l and 1.79, respectively, showing a variability of 86.6 and 38.7%, respectively, and a residual variability of 13.0%. Significant differences (P < 0.05) were found for the total plasma clearance (Cl) but not for the intrinsic plasma clearance (Clu) values, despite their tendency to decrease with the dose. If TDM is to be used for valproic acid, it is the free serum levels that should be determined, especially if high doses are administered, because the total serum levels are not a true reflection of the free ones, as is the case of other anti-epileptic drugs.

Adult↗
PubMed1992

Population pharmacokinetics of imipramine in children.

The population pharmacokinetics of imipramine (IMI) and its active metabolite desipramine (DMI) have been evaluated using 177 IMI and DMI serum levels from 49 enuretic children (6-13 y) on IMI treatment. Standard two stage (STS) and maximum likelihood (ML) methods were used to estimate fixed and random effect parameters of IMI. Simultaneous estimation of the drug and metabolite parameters was carried out by the STS method. The mean value of the elimination constant of the drug and metabolite were 0.0425 h-1 and 0.0359, h-1 respectively. Significantly higher variability was found in the pharmacokinetic parameters of the metabolite. According to these estimated pharmacokinetic parameters, the recommended dose for enuretic children should be 1.7 mg.kg-1.day-1. The population pharmacokinetic parameters obtained in the study permit dosage individualisation using a bayesian algorithm.

Adolescent↗
PubMed1992

Population pharmacokinetics of gentamicin in premature infants.

The population kinetics of gentamicin were studied in 97 newborn patients with a gestational age ranging between 28 and 43 weeks and a postnatal age ranging between 2 and 30 days undergoing routine therapeutic monitoring of their serum gentamicin levels. The individual kinetic analysis of serum drug levels was performed using a single-compartment model. The clearance and apparent distribution volume were calculated in each patient. The population model employed assumes the existence of residual variability in the serum concentrations and interindividual variability in the pharmacokinetic parameters. The effects of demographic variables on the clearance, distribution volume, and optimum daily dose of gentamicin were established using multiple linear regression. Gestational age is the best predictive variable of the clearance and the optimum dose/day in the whole population studied. In the premature infant patients, the predictive capacity increases with postconceptional age. Weight is a good predictive variable of all of the parameters, especially of the apparent distribution volume in the overall population of newborns. Analysis of the population kinetic behavior and optimum dose/day in each subgroup recommends that the interval of drug administration should be increased, keeping the same dose/day ratio, due to the tendency of the drug to accumulate its long half-life, especially in premature babies.

Birth Weight↗