A reliable method to quantify sildenafil and its metabolite N-demethylsildenafil by HPLC in plasma of children.

The aim of this study was to develop a simple method for quantifying plasma levels of sildenafil and its metabolite by liquid chromatography with a C18 reverse-phase column and UV detection. For both compounds, linearity was assessed in the range from 10 and 1 000 ng · ml-1 and had correlation coefficients of r=0.995 and r=0.997 for sildenafil and its metabolite, respectively. The inter- and intra-day coefficients of variation was<5.3%. The limits of detection and quantification were 1 and 10 ng · ml-1. Drug levels were determined satisfactorily in two patients. A simple and reliable method was developed for use in children with Pulmonary Arterial Hypertension under treatment with sildenafil.

Preparation and evaluation of unitary doses of propafenone used in children with supraventricular tachycardia: a pilot study.

PURPOSE: The aim was to prepare and evaluate unitary doses of propafenone (UDP) used in children with supraventricular tachycardia. METHODS: UDP were prepared from four brands of tablets at doses of propafenone, 11, 25 and 90 mg, used in the Cardiology Service of this Institute. The stability of doses was determined at 20±5°C and 40°C for up to day 30. Besides, a weight variation test was performed. Plasma levels of propafenone were determined at steady state in 3 children diagnosed with supraventricular tachycardia under treatment with UDP. Concentrations of drug in blood were measured using a high pressure liquid chromatography method, previously validated. RESULTS: The stability of UDP, showed no significant statistical differences (p > 0.05) between doses or brands up to day 30, at both temperatures. The coefficient of variation from the weight variation was less than 6%. The plasma levels of propafenone at steady state were: patient 1, 31.57 ng/ml; patient 2, 226.46 ng/ml; and patient 3, 221.29 ng/ml. CONCLUSIONS: The actual administered dose for the patients could vary up to 6%, and doses prepared from different brands of tablets remain stables for up to day 30 at both temperatures. UDP is a temporal, safe and alternative option when pediatrics formulation of this drug is lacking.

Patterns of drug consumption in relation with the pathologies of elderly Mexican subjects resident in nursing homes.

PURPOSE: To describe the patterns of drugs consumed by the male and female elderly living in Mexican private and public nursing homes. METHODS: Three hundred and fifty elderly participants from four nursing homes (2 private and 2 public) were selected for the six month study: 108 subjects were excluded; the remaining 242 were between 65 and 100 years old; 123 were females and 119 males. A complete clinical history was taken and clinical files were reviewed. RESULTS: Of the 242 elderly studied, 193 took diverse medications and 28.5% were at risk of some type of drug interaction. The groups of drugs more frequently consumed were vitamins and anti-anemic medications, followed by cardiovascular drugs. Females consumed greater number of drugs. They also consumed more drugs simultaneously. CONCLUSIONS: There is a need to monitor the elderly for their drugs pattern use.

[Bayesian prediction of chloramphenicol blood levels in children with sepsis and malnutrition]. / Predicción bayesiana de las concentraciones séricas de cloranfenicol en niños con sepsis y desnutrición.

OBJECTIVE: To validate the population pharmacokinetic parameters of chloramphenicol in pediatric patients with sepsis and malnutrition (PPSM) using a bayesian forecasting program. DESIGN: Retrospective evaluation of predictive performance of a bayesian program in PPSM. SETTING: Tertiary care center. PATIENTS: Fifteen MPSP and ten NMPSP that receiving treatment with chloramphenicol. METHODS AND MAIN RESULTS: In the first part of the study, the medical records of 10 MPSP and 10 NMPSP who had received treatment with chloramphenicol were reviewed. The population pharmacokinetic parameter values for each group were estimated using a nonparametric expectation maximization algorithm (NPEM). In the second part, data gathered from five other MPSP receiving chloramphenicol were entered into a bayesian program. Chloramphenicol pharmacokinetic values for each of these five patients were estimated, first using the values of NMPSP as a priori distribution and then repeating the analysis using the MPSP values. The bayesian serum chloramphenicol concentrations predicted for each population model were compared with the actual peaks and troughs. The specific model for MPSP permitted forecasting the peak and trough serum chloramphenicol concentrations with less bias and a better precision compared with the NMPSP population model. CONCLUSIONS: These data indicate that chloramphenicol pharmacokinetics in PPSM can be predicted with minimal bias and good precision using a bayesian forecasting program, allowing a better control of the chloramphenicol serum concentrations. In addition, the limited number of samples required by the bayesian method may represent an important economical benefit for the patient.

Influence of nutritional status on the pharmacokinetics of acetylsalicylic acid and its metabolites in children with autoimmune disease.

BACKGROUND: It is unknown whether nutritional status associated with autoimmune disease alters the pharmacokinetics of acetylsalicylic acid (ASA) and its metabolites. OBJECTIVE: We studied the effects of the nutritional status of children with autoimmune disease on the disposition of ASA and its metabolites. DESIGN: A prospective, open-label study was performed with 21 children aged 3-15 y who required ASA therapy. Children received 25 mg ASA/kg orally. Blood samples were drawn before and 0.5, 1.0, 2.0, 4.0, 8.0, 12.0, and 24.0 h after ASA administration; urine samples were collected at different intervals. ASA and its metabolites were measured in plasma and urine. Nutritional status was assessed previously. RESULTS: The ASA maximum plasma concentration, area under the curve, and total clearance were significantly lower in underweight children than in normal-weight children. The elimination rate constants of gentisic acid (GA), salicyluric acid (SUA), and salicylic acid (SA) in plasma were slower for underweight children than for normal-weight children. The distribution volume of SUA increased significantly (r = 0.92) when the deficit percentage in weight-for-height increased. Underweight children excreted less GA and SA, but more SUA, than did normal-weight children. CONCLUSIONS: These observations suggest a decrease in the hydrolysis and oxidative reactions of the metabolic pathway of ASA and its metabolites in underweight children. The study illustrates the need for pharmacokinetic data to establish the individual doses of drugs, particularly in conditions that alter nutritional status.

[Cefuroxime Bayesian pharmacokinetics in severely ill septic children]. / Farmacocinética bayesiana de cefuroxima en niños infectados gravemente enfermos.

OBJECTIVE: To estimate the cefuroxime pharmacokinetic parameters in critically ill pediatric septic patients using a Bayesian pharmacokinetic method and three serum drug assays per patient. DESIGN: Cross-sectional study of critically ill pediatric patients undergoing therapeutic monitoring of cefuroxime serum concentrations. SETTING: Tertiary care center. PATIENTS: Nine critically ill pediatric patients with sepsis and septic shock treated with cefuroxime. METHODS: Timed serum concentrations of cefuroxime were obtained in each patient. The Vd (volume of distribution) and the Kel (constant of elimination) were estimated by means of a Bayesian iterative two-stage algorithm, using the information of three serum drug concentrations per patient at optimal times. The parameters were also estimated by the traditional method of non linear least square regression in eight samples. RESULTS: The Bayesian Vd was very similar to the traditional Vd with a correlation coefficient of 0.99 and a small bias of -0.04 L/kg whereas the Kel had a correlation of 0.90 and bias of -0.29 h-1. The mean Bayesian Vd was 0.68 L/kg, a larger value than that reported in non critically ill patients. CONCLUSIONS: We offer a tentative cefuroxime pharmacokinetic model for critically ill pediatric septic patients which may be useful for the control of cefuroxime serum concentrations. Also, our study underscored the potential usefulness of a Bayesian pharmacokinetic approach as a tool for therapeutic drug monitoring in critically ill patients.

Plasmatic levels of theophylline in asthmatic patients. Comparative evaluations of two different methods.

BACKGROUND: There are several criteria to choose an analytical method for drug monitoring. Such methods have to comply with standard values and quality control as well as other subjective features such as cost and the time consumed to obtain quantification (TCOQ). The purpose of this work was to compare two methods used to quantify plasmatic levels of theophylline in asthmatic patients as support to choose the best method. METHODS: We analyzed plasma samples from 30 asthmatic pediatric patients at the pediatric service of the Hospital General de México, who were under treatment with theophylline and whose monitoring of drug levels was indicated. Plasma samples were analyzed by liquid chromatography (HPLC) and by enzyme immunoassay (EMIT), and were then compared with respect to reliability, as well as cost and TCOQ. RESULTS: The difference of the plasmatic levels of theophylline quantified by both methods was not significant (p > 0.05); both showed a good correlation index (r = 0.995), and both were reliable based on other validity parameters. However, TCOQ for HPLC was 20.0 +/- 5.5 min (mean +/- SD) for each sample analyzed, and 2.3 +/- 0.5 for EMIT. With respect to the cost of each analysis, HPLC required 2.3 +/- 0.5 USD (mean +/- SD) and EMIT 4.5 +/- 0.3 USD. CONCLUSIONS: Analytical methods used to quantify plasmatic levels of theophylline based on HPLC and EMIT proved to be suitable, because they fulfilled the criteria and standard values regarding quality control, although laboratorists have to select subjectively the best method according to cost and TCOQ, since HPLC was less expensive, and EMIT was more rapid.