Pharmacokinetics of sildenafil in children with pulmonary arterial hypertension.

BACKGROUND: Recently, sildenafil was introduced to treat pulmonary arterial hypertension (PAH); however, there are currently few studies on the pharmacokinetics of sildenalfil in children. Therefore, we aimed to carry out a pharmacokinetic study of sildenafil in children with PAH using a single dose. METHODS: Twelve children diagnosed with PAH, consisting of with ten males and two females, were recruited for the study after obtaining written consent from their parents or guardians. Blood samples were obtained predose and at 0.25, 0.5, 1, 2, 4, 8 and 12 hours after the oral administration of 1 mg/kg of sildenafil using an extemporal pediatric formulation developed in our laboratory. The samples were analyzed using a previously validated high performance liquid chromatography method. RESULTS: A pharmacokinetic analysis using the WinNonlin 3.1 program that considered the Akaike information criterion (AIC) for selecting a more adjustable model was performed. The following pharmacokinetic parameters were obtained: maximal concentration (Cmax): 366±179 ng/mL, time to maximal concentration: 0.92±0.30 hours, elimination half-life (t1/2): 2.41±1.18 hours, total clearance (CLtot/F): 5.85±2.81 L/hour, volume of distribution (Vd/F): 20.13±14.5 L, absorption rate constants (Ka): 0.343 hour-1, elimination rate (Ke): 0.35 hour-1, area under curve from zero to infinity: 2061±618 ng/mL/hour. The data of all patients adjusted to the model of one compartment were corroborated using AIC. CONCLUSIONS: The parameters Ka, Ke and t1/2 were found to be similar to those reported in adults; however, the values of Cmax and Vd/F were significantly higher. Based on these findings, we propose that treatment regimen of sildenafil be adjusted in children with PAH.

Body Composition, Nutritional Profile and Muscular Fitness Affect Bone Health in a Sample of Schoolchildren from Colombia: The Fuprecol Study.

The objective of the present study is to investigate the relationships between body composition, nutritional profile, muscular fitness (MF) and bone health in a sample of children and adolescents from Colombia. Participants included 1118 children and adolescents (54.6% girls). Calcaneal broadband ultrasound attenuation (c-BUA) was obtained as a marker of bone health. Body composition (fat mass and lean mass) was assessed using bioelectrical impedance analysis. Furthermore height, weight, waist circumference and Tanner stage were measured and body mass index (BMI) was calculated. Standing long-jump (SLJ) and isometric handgrip dynamometry were used respectively as indicators of lower and upper body muscular fitness. A muscular index score was also computed by summing up the standardised values of both SLJ and handgrip strength. Dietary intake and degree of adherence to the Mediterranean diet were assessed by a 7-day recall questionnaire for food frequency and the Kidmed questionnaire. Poor bone health was considered using a z-score cut off of ≤-1.5 standard deviation. Once the results were adjusted for age and Tanner stage, the predisposing factors of having a c-BUA z-score ≤-1.5 standard deviation included being underweight or obese, having an unhealthy lean mass, having an unhealthy fat mass, SLJ performance, handgrip performance, and unhealthy muscular index score. In conclusion, body composition (fat mass and lean body mass) and MF both influenced bone health in a sample of children and adolescents from Colombia. Thus promoting strength adaptation and preservation in Colombian youth will help to improve bone health, an important protective factor against osteoporosis in later life.

Normative data for calcaneal broadband ultrasound attenuation among children and adolescents from Colombia: the FUPRECOL Study.

UNLABELLED: Quantitative ultrasound (QUS) has been found to be a safe and reliable method for evaluating bone mineral density (BMD). Using calcaneal QUS techniques, the current study contributes to remedying this gap in the literature by establishing normative data among children and adolescents from Colombia. INTRODUCTION: Minimal data on BMD changes are available from populations in developing countries. BMD reference values for children and adolescents have not been published for a Latin-American population. The aim of this study was to establish a normal reference range of calcaneal broadband ultrasound attenuation (BUA) in Colombian children and adolescents with ages ranging from 9 to 17.9 years. METHODS: A sample of 1001 healthy Colombian youth (boys n = 445 and girls n = 556), children, and adolescents (9-17.9 years old) participated in the study. A calcaneus QUS parameter (BUA) was obtained for boys and girls, stratified by age group. Furthermore, height, weight, fat mass percentage, and body mass index were measured. Centile smoothed curves for the third, tenth, 25th, 50th, 75th, 90th, and 97th percentiles were calculated using the LMS method (L [curve Box-Cox], M [curve median], and S [curve coefficient of variation]). RESULTS: Mean (± SD) values for the participants' anthropometric data were 12.9 ± 2.3 years of age, 45.2 ± 11.5 kg weight, 1.51 ± 0.1 m height, 19.5 ± 3.1 kg/m(2) BMI, and 69.5 ± 17.1 dB/MHz BUA. Overall, all variables were significantly higher in boys except in BMI and body fat percentage. Girls generally had higher mean calcaneal BUA (dB/MHz) values than the boys, except in the age ranges 16 and 17.9, p > 0.05. In addition, the BUA (dB/MHz) increased with age throughout childhood and adolescence and reached a plateau by age 15-17.9 for girls. CONCLUSIONS: For the first time, our results provide sex- and age-specific BUA reference values for Colombian children and adolescents aged 9-17.9 years. A more specific set of reference values is useful for clinicians and researchers and informs clinical practice to monitor bone mineral status.

Unintentional poisoning with drugs in a Mexican pediatric population.

In Mexico, more than 70 % of acute pediatric poisoning is caused by medicines. The age groups at greatest risk of drug poisoning are those between 2 to 5 years and 14 to 18 years; although in this last group, drug ingestion is usually intentional. The purpose of our study was to determine the frequency of unintentional drug poisoning in the pediatric population attended in a tertiary care hospital in Mexico, and to review the rescue procedures applied in specific cases. A retrospective and descriptive study was performed through revision of clinical records, obtained from patients attended at the National Pediatrics Institute from January 1995 to June 2005. One hundred and thirty nine (139) records, 62 females and 77 males, median age 2 years with clinical diagnosis of drug poisoning were reviewed. Poisoning was confirmed in 23.7% of the cases by determination of drug plasma concentration. The most frequent causes of drug poisoning were analgesics (42.3 %), from which 60 % corresponded to acetylsalicylic acid and 40 % to acetaminophen; antiepileptics (22.9 %), anxiolytics (17.9 %) and other drugs (16.3 %). From our results, we concluded that self-medication was unlikely due to the early age of patients, unless ingestion of the drug was accidental. No case needed more than 24 h of hospitalization, and no patient died due to poisoning. Specific cause of poisoning was that, at early ages, doses must be administered according to the infant's weight, which poses a risk of poisoning.

Effect of mannitol on the pharmacokinetics of amikacin in wistar rats

The study analyzed the effect of mannitol on the pharmacokinetics (PK) of amikacin. Adult Wistar rats were treated as follows: Group 1 (G1) received mannitol for three days, Group 2 (G2) received mannitol plus 10 mg/kg of amikacin simultaneously, and Group 3 only amikacin. The PK study was conducted on the 4th day. For which, blood samples were drawn at fixed times during 24 h and immunoenzymatically analyzed. Results revealed significant differences (p<0.05) between the groups, e.g. Cmax were 62.26 ± 15.75 µg/ml for G1, 72.63 ± 24.80 µg/ml for G2 and 68.61 ± 27.40 µg/ml for G3. The AUC also differed in the three groups, being largest for G2, 222.52 ± 47.30 µg/ml/h, and smallest for G1, 135.59 ± 39.00 µg/ml/h. Alteration of the PK parameters observed between the groups must be considered when both drugs are prescribed, although human studies are necessary to confirm the results.

O estudo analisa o efeito do manitol na farmacocinética (PK) da amicacina . Ratos adultos Wistar foram tratadas da seguinte maneira: o grupo 1 (G1) recebeu manitol durante três días. Ao grupo 2 (G2) se administrou manitol e 10 mg/kg de amicacina, ao mesmo tempo. Finalmente, o grupo 3 (G3) recebeu somente amicacina. No quarto día se realizou o estudo de PK nos três grupos. Para isso, foram retiradas amostras de sangue, em tempos pre-determinados, durante 24 horas, que foram analisadas por métodos imunoenzimáticos. Os resultados mostraram diferencas significativas (p < 0.05) entre os grupos. Po exemplo, os valores obtidos de Cmax foram 62.26 ± 15.75 µg/ml para G1, 72.63 ± 24.80 µg/ml para G2 e 68.61 ± 27.40 µg/ml para o Grupo 3. A AUC foi também diferente entre os três grupos: a maior para G2, com, 222.52 ± 47.30 µg/ml/h, e a menor para G1, com um valor de 135.59 ± 39.00 µg/ml/h. A alteração dos parámetros de PK entre os grupos debe ser considerada quando se administram os dois farmacos simultaneamente. No entanto, é necessario realizar estudos em seres humanos para confirmar os nossos resultados.