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Biomedical subjects

A Domínguez-Gil

Publications and source records attributed to A Domínguez-Gil.

At least 19 recordsLinked to original sources
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↗
PubMed1992

Dosage optimization methods applied to imipramine and desipramine in enuresis treatment.

Three methods for estimating maintenance dosage requirements of imipramine were compared retrospectively in 146 enuretic patients. The dosing methods evaluated included individual (serum levels data) and/or population (average pharmacokinetic parameter) information. The use of imipramine and desipramine serum concentrations, as opposed to average population parameters only, improved forecast precision and accuracy for dosage individualization. The clinical acceptability of this was achieved through knowledge of a single serum concentration. No significant differences were seen between non-linear regression and the Bayesian method, this is in agreement with the high contribution of the patient's data to the Bayesian fitting (FF = 0.8). When one or two serum level data were available, a better performance was obtained by estimating pharmacokinetic parameters than level:dose ratios.

Adolescent↗
PubMed1992

A computer program (DCN) for numerical convolution and deconvolution of pharmacokinetic functions.

A program adapted for use on microcomputers (DCN) has been developed which permits one to perform operations of numerical convolution and deconvolution using polyexponential functions, that are often implemented in pharmacokinetic analysis. The program is written in Microsoft GWBASIC and can be used in personal computers with no modification. The user supplies information relating to the coefficients and exponentials defining the polyexponential equation of the response and weighting functions and the program performs the deconvolution operation by numerical integration using trapezoidal rule and provides numerical and graphic information concerning the input function. The program can be applied to the deconvolution of many linear pharmacokinetic systems and allows one to solve problems related to drug release, absorption, distribution, as well as others. Additionally, the program is able to perform the convolution operation if information about the input and weighting functions and is also able to simulate pharmacokinetic processes. The efficacy of the program was evaluated by comparison with several deconvolution algorithms, in particular that proposed by Veng-Pedersen and Iga.

Algorithms↗
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↗
PubMed1991

Distribution kinetics of netilmicin in human blister fluid: effect of renal impairment.

The pharmacokinetics of netilmicin in plasma and blister fluid were compared in 10 healthy volunteers with normal renal function and 10 voluntary patients with varying degrees of renal impairment. Netilmicin kinetics in plasma were characterized by an open two-compartment kinetic model. For the study of the kinetics of the antibiotic in blister fluid a specific kinetic distribution model was employed. In the healthy volunteers the plasma kinetics of netilmicin showed a behaviour similar to that of other aminoglycoside antibiotics, although a high blister/plasma partition coefficient was obtained, with a mean value of 4.27 +/- 1.65. The transfer of netilmicin in blister fluid governed by the constants K1b/Vb and Kbl had mean values of 0.19 +/- 0.09 h-1 l-1 and 0.25 +/- 0.10 h-1, respectively. In the patients with renal impairment plasma and blister fluid antibiotic levels showed a progressive accumulation. In these patients the affinity of netilmicin for blister fluid was significantly altered. The blister/plasma partition coefficient in this group of patients had a mean value of 2.65 +/- 1.33; the decrease being statistically significant (p = 0.023) with respect to the value obtained in the healthy volunteers. Similarly, the exit constant of netilmicin from blister fluid (Kb1) showed a statistically significant increase (p = 0.035) in the patients with renal impairment. The findings point to a loss of affinity of netilmicin for blister fluid as a result of renal impairment. Linear and logarithmic relationships were established between some pharmacokinetic parameters and creatinine clearance. Dosage schedules are proposed for netilmicin in patients with renal impairment.

Adult↗
PubMed1991

Effects of two cations on gastrointestinal absorption of ofloxacin.

A study was performed to establish the effect of Al3+ and Fe2+ cations on the absorption of ofloxacin when it is administered orally at a dose of 200 mg. The study was carried out with nine volunteers, who each received three treatments (A [200 mg of ofloxacin], B [200 mg of ofloxacin plus 11 g of colloidal aluminum phosphate], and C [200 mg of ofloxacin plus 1,050 mg of FeSO4]) according to a Latin square design; the washout period was 1 week. The analytical technique was a microbiological diffusion method. The pharmacokinetic parameters were calculated from the cumulative urinary excretion data and from a sigma-minus plot. The total amount of ofloxacin excreted in urine had a mean value of 163.59 +/- 22.13 mg when ofloxacin was administered alone, 152.41 +/- 18.76 mg when it was administered with Al3+, and 146.49 +/- 14.85 mg when it was administered with Fe2+. No statistically significant differences were found in the F values (fractions of dose absorbed) obtained with ofloxacin alone and ofloxacin plus Al3+ (P = 0.341). When ofloxacin alone was compared with joint administration with Fe2+ the value of F decreased 10.85%; this difference is statistically significant (P = 2.623 x 10(-2)).

Adult↗
PubMed1991

Biotransformation kinetic of binifibrate and identification of its metabolites.

The metabolism of binifibrate was studied in 10,000 g supernatant fractions from rat liver. Binifibrate was found to be completely biotransformed into clofibric acid and nicotinic acid at 60 min from the start of incubation through a series of intermediate products among which glycerol dinicotinate was identified. The biotransformation constant of binifibrate into its different metabolites proved to be 0.11 +/- 0.025 min-1. The formation of clofibric acid follows a first-order kinetic process characterized by its corresponding rate constant (kc), proving to be 0.043 +/- 0.017 min-1. The amount of clofibrate was 0.78 +/- 0.16 mumol/ml, showing that it is not biotransformed later in the incubation mixture. The formation constant of nicotinic acid (kn) was 0.067 +/- 0.020 min-1 and the amount of substance contained in the incubation mixture (0.94 +/- 0.25 mumol/ml shows that it is later biotransformed in the incubation mixture through the previously described metabolic processes.

Animals↗
PubMed1990

Pharmacokinetics of dibenzylamine administered in a sustained drug delivery system with cefazolin.

The pharmacokinetics of dibenzylamine administered in a sustained drug delivery system with cefazolin was studied after i.m. administration of a dose of 1250 mg to healthy volunteers. The serum and urine levels of dibenzylamine were determined by a GLC technique using a specific nitrogen-phosphorus detector. Characterization of the kinetic parameters was performed by applying compartmental and non-compartmental analysis. Dibenzylamine was found to reach concentrations close to 300 ng ml-1 approximately 5 h after administration. The elimination constant had a value of 0.832 +/- 0.821 h-1 (mean +/- S.D.), which is higher than the release constant of the derivative (0.109 +/- 0.072 h-1) (mean +/- S.D.). These results show that release of dibenzylamine may be considered the limiting kinetic process, which governs the elimination of the product from the organism. Only a small amount of dibenzylamine is excreted in urine unchanged 3.43 +/- 3.28 per cent (mean +/- S.D.). Using the pharmacokinetic parameters calculated for dibenzylamine, a prediction has been made of the concentrations reached in a multiple dosage regimen after administration of a dose of 1250 mg every 24 h. The accumulation factor was 1.09.

Adult↗
PubMed1990

The influence of clinical and pharmacological factors on enuresis treatment with imipramine.

1. The aim of this study has been to evaluate the response to imipramine treatment in enuretic children through the use of a series of clinical and pharmacological variables and by applying a multivariate (principal components) analysis technique. 2. The study was carried out on 146 children whose ages ranged from 5 to 14 years, and who received variable doses of imipramine (12.5 to 100 mg day-1). 3. The quantitative variables analyzed were: drug dosage, serum levels of imipramine and its metabolite desipramine, the relationship between them both, the duration of treatment, age and weight. 4. The qualitative variables were: compliance, presence of side-effects, enuretic and/or psychiatric antecedents, intelligence quotient (I.Q.), the existence (or absence) of related pathologies, sex, and the type of enuresis. 5. The response to treatment was quantified by means of the percentage of decrease in frequency of enuresis as compared with the initial frequency. 6. The results obtained show that the variables which are most associated with the reduction of enuresis are, in decreasing order: the dosage of imipramine administered, the duration of treatment, compliance and the level/dose ratio for the sum of the drug and metabolite levels.

Adolescent↗
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

Pharmacokinetics of rectal ketamine in children.

We have studied the pharmacokinetics of ketamine administered rectally in a dose of 10 mg kg-1 to five children aged 6-9 yr and mean weight 28.80 (SD 6.55) kg. An acceptable level of anaesthesia was not obtained in any patient. Despite this, the degree of analgesia obtained was good and no child required further administration of analgesics during the postoperative period. Tolerance to the suppositories was excellent. The absorption of ketamine was found to be relatively fast, with a median peak concentration of 160 ng ml-1 (range 96-250 ng ml-1) at 0.75 h (range 0.50-1.00 h) after administration. The plasma concentrations of norketamine were greater than those of the parent drug, with a maximum of 510 ng ml-1 (range 450-810 ng ml-1) at 0.81 h (range 0.50-1.00 h) after administration. The medians of the half-lives of ketamine and norketamine were 3.15 h and 2.56 h, respectively (range 1.57-4.95 h and 1.47-5.30 h, respectively).

Administration, Rectal↗
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↗
PubMed1989

Predictive techniques applied to imipramine therapeutic drug monitoring.

The aim of this study was to establish the performance of pharmacokinetic methods employing little data on serum drug concentrations obtained in routine therapeutic drug monitoring of imipramine. Forty-three and 123 serum levels were obtained in 8 adult depressive patients (aged 57-80 y) and 34 enuretic children (aged 5-13 y), respectively. Forecasting of the serum concentrations was performed based on mean population pharmacokinetic parameters (method A), with knowledge of one steady-state serum concentration (method B), and from two or more steady-state serum concentrations (method C). The accuracy and precision of each method were evaluated from the mean prediction error (ME) and from the root mean squared prediction error (RMSE), respectively. The values of ME and RMSE of methods B and C proved to be significantly lower than those found using method A. Method C was the most precise and accurate in both populations. Method A underestimates the serum concentrations observed in adults (ME greater than 0) but overestimates them in children (ME less than 0), although to a lesser extent. The study shows that it is possible to obtain a good estimation of individual dosage needs from one or more serum concentrations obtained at steady state. Clinical application of these methods (B and C) yields an increase in the efficiency and safety of the treatment, particularly in special populations such as geriatric and pediatric patients.

Adolescent↗
PubMed1988

High levels of tricyclic antidepressants in conventional therapy: determinant factors.

The incidence of potentially toxic serum levels (greater than or equal to 400 ng/ml) was analyzed in a group of 196 monitored patients on a standard dosage regimen (75-225 mg/day) of several antidepressants: imipramine, amitriptyline, nortriptyline, maprotiline and clomipramine. Mean incidence was 12%. The maximum antidepressants serum levels in these patients ranged from 403 to 1,776 ng/ml. The drug/metabolite ratio was 1.5 +/- 0.7. Only in 23% of the cases did the clinical symptoms allow us to suspect the presence of potentially toxic serum levels. The factors that may contribute to the appearance of high serum levels were analyzed; these are: association of neuroleptic agents to the antidepressant therapy, advanced age and administration of doses above 2.5 mg/kg/day. In 64% of the patients, the clinical criteria suggested the need for a reduction in the dose, with a mean value of 42%.

Adult↗