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.

Effect of orlistat on lipid peroxidation, Na+, K+ ATPase, glutathione and serotonin in rat brain.

The aim of this study was to evaluate the effect of orlistat, a drug used in weight loss, on 5-HT and indicators of oxidative stress in rat brain. Orlistat, 12 mg/kg was administered to Wistar rats as single dose or successive doses on 3 consecutive days. Blood glucose and oxidative stress indicators were detected by measurement of lipid peroxidation, Na+, K+ ATPase, glutathione and serotonin levels using previous validated methods. The levels of glucose decreased in rats receiving successive doses. The activity of Na+, K+ ATPase and total ATPase was reduced in rats receiving successive doses, while the level of lipid peroxidation increased slightly in both groups. Glutathione underwent significant reduction in the successive doses group (p < 0.05). 5-HT increased significantly after single dose treatment (p < 0.05). Orlistat can induce pro-oxidant effects in the brain due to alteration of serotonergic metabolism and the reduction of glutathione.

[Hepatic anatomophatologic injuries by extrahepatic biliar tract obstruction in mice]. / Lesiones anatomopatológicas hepáticas por la obstrucción de la vía biliar extrahepática en ratones.

UNLABELLED: The aim is to evaluate the liver damage due to an experimental animal model based in the temporal obstruction of biliar extrahepatic duct and determine the relation between obstruction and severity of damage through time. METHODS: We used 20 adults male mice going from 25 to 35 g weight, previous to general anesthesia, a surgical incision was applied and biliar duct were localized and tied using linen cloth. Six animals were sacrificed each time at 1, 7 and 15 days of treatment, the hepatic, lung, kidney, hearth and brain were obtained for histopatologic analysis using optic microscope. RESULTS: In the first day 20% of hepatic samples, light lesions as sinusoidal congestion and dilation of portal vessel with hepatocelular biliar stasis were found. In 7th day additional lesions were found as accumulations of biliar pigments in the cholangiols, proliferation of portal collagens and light pericholangiolar proliferation in 60% of samples. At 15th day, severely lesions as hamartomatous proliferation of cholangiols and portal fibrosis of biliar ducts that deformed the boundary plaque and lobular in 15% of samples. In brain, hearth, and lung samples showed vascular dilation and severe congestion, except at 15th day, when samples of kidneys showed biliar pigment precipitation in lumen of collets ducts. CONCLUSIONS: The proposed method is useful to study the chronologic relationship of anatomophatologic damage produced by biliar obstruction.

Bioavailability of ranitidine in healthy Mexican volunteers: effect of food.

Is well known that food can affect the bioavailability of several drugs, its impact is major for those drugs that have to act near of drug absorption. Documentation about alterations of ranitidine bioavailability by effect of food is poor. The purpose of this work was to evaluate the effect of food over the bioavailability of ranitidine. Twenty healthy Mexican volunteers were included for the study. The study was made in two stages, in the first one the volunteers had 12 hour fast and took a 300 mg of oral dose of ranitidine (without food, WOF) and blood samples were drawn. Two weeks later, the volunteers took a normal diet just before ranitidine intake (with food, WF). The area under the curve (AUC) was 30% greater in WOF, Cmax was 921.5 ng/ml (WF) vs. 1685.2 (WOF), and t1/2 was 2.70 +/- 1.38 (WF) h vs 3.66 +/- 1.34 (WOF). The AUC, Cmax and t1/2 were statistically different. It is evident that there are differences in the drug disposition due to the presence of food, then, it is possible that the efficacy of ranitidine as inhibitor of gastric secretion being limited by food.

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.

[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.

[Post-dosage loading concentrations of theophylline and pharmacokinetic study after the fifth maintenance dosage in premature newborns with apnea]. / Concentraciones de teofilina postdosis de impregnación y estudio farmacocinético en la quinta dosis de mantenimiento en recién nacidos pretérmino con apneas.

From a group of 50 premature newborns with central and mixed apnea, 34 received a loading dose of 4.3 mg/kg intravenous theophylline (group I) and 16 received 6 mg/kg orally (group II); the maintenance dose was 0.86 and 1 mg/kg every eight hours, respectively. Mean maximum serum concentrations after the loading dose were 5.8 +/- 2.3 mcg/mL in 25 newborns from group I, and 6.6 +/- 1,3 mcg/mL in 8 newborns from group II (P less than 0.20). Mean maximum concentration after the fifth maintenance dose was 7.5 +/- 1.7 mcg/mL in 26 newborns from group I, and 5.8 +/- 1.4 mcg/mL in 16 newborns from group II (P = 0.001); mean minimum concentration was 5.3 +/- 1.6 mcg/mL and 4.5 +/- 1.4 mcg/mL, respectively (P greater than 0.10). Mean clearance was 30.21 +/- 11.03 and 27.1 +/- 7.7 mL/kg/h; mean apparent distribution volume was 0.5 +/- 0.25 and 0.76 +/- 0.32 L/kg; elimination rate constant was 0.049 +/- 0.04 and 0.040 +/- 0.03/h-1 for both groups respectively, with significant differences between groups only in the apparent distribution volume (P less than 0.001). Half-life time (T1/2) was from four to 118 hours. The study population was divided into three groups according to half-life time: those with a half-life time of lesser than 20 hours (47.6%); an intermediate half-life time of from 20 to 30 hours (23.8%); and a long half-life time of more than 31 hours (28.6%).(ABSTRACT TRUNCATED AT 250 WORDS)

[Blood levels of phenytoin. Pharmacokinetics and individualization of dosages in controlled children with crises and with persistence of crises]. / Niveles séricos de fenitoína. Farmacocinética e individualización de dosis en niños con crisis controlados y con persistencia de las crisis.

The pharmacokinetics of phenytoin was evaluated using the Michaelis-Menten technique in children with seizures seen at the Outpatient Ward, in order to adjust their medication dosages based on a clinical-pharmacological relation. The children were divided into two groups: Group A (controlled seizures) and group B (persistent seizures). Each group of children were orally given 7 mg/kg of phenytoin. Their serum levels were measured using enzymatic immunoassay at one, two, four, eight and 12 hours after taking the medication. There was a significant correlation (P less than 0.05) between the average saturation constant (Km) and the maximum speed (Vmax) with age and the doses administered in group A, which showed a lesser metabolic capacity than group B. There was also a significant correlation (P less than 0.05) when predicting the levels in each group. Clinically, the patients group A were controlled while those in group B witnessed a lesser frequency and intensity of the seizures in six patients, two were controlled and two others remained the same. The data shows a clinical-pharmacological correlation in children difficult to control, and improves the dosaging criteria used each individuals needs.

[Relation between dose, plasma concentration and therapeutic effect of theophylline in children with sleep apnea]. / Relación entre la dosis, concentración plasmática y efecto terapéutico de teofilina en niños con apnea del sueño.

The plasma concentration of theophylline was determined in twelve children with infantile sleep apnea (average age 48.5 days). The purpose of the study was to correlate concentrations with the dosages given, the therapeutic response and any adverse effects which could arise. In addition, other pharmacokinetic values were found, half-life (t 1/2) and clearance concentrations (Clss). The oral maintenance dose used was 4 mg/kg/24 h. The serum concentration of theophylline was determined by a homogeneous immunoassay enzyme technique (EMIT). A bad correlation was found (r = 0.45) between the oral dosage given and the plasma concentrations found. This was probably due to variations in the clearance of the drug. Yet, plasma concentrations fell between 3.0 and 12.6 micrograms/mL, enough to satisfactorily control apneic episodes in all the children included in the study without undesirable side-effects. Only one patient had some trouble in falling asleep and showed signs of irritability. The half-life was 13.30 +/- 7.46 hours and Clss was 36.64 +/- 12.98 mL/h/kg. In general, our results correlate with those reported in the literature. The accuracy of the pharmacokinetic parameters with two samples is reliable, therefore avoiding the use of multiple sampling in this group of children.