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.

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.

Frequency of suicide attempts by ingestion of drugs seen at a tertiary care pediatric hospital in Mexico.

Suicide is a complex behavior with biological, psychological and social causes. It has predisposing family factors such as domestic violence, psychiatric disorders and parents' alcohol abuse. Suicides have increased in children and adolescents in the last decades and it is now the third leading cause of death. Mexico has the second place in mortality in adolescents between 10-14 years old, of which 21.9 % are suicides. This study aimed to determine the frequency of suicide attempts using drugs in children and adolescents in a tertiary care hospital and to identify the causes. A retrospective and descriptive study was performed considering socioeconomic, cultural and biological issues related to suicide attempts using drugs in children and adolescents who were attended at the National Institute of Pediatrics from January 1995 to March 2005. A total of 141 drug intoxication cases were detected including 47 suicide attempts; 25 girls and 22 boys, with a median of 13 years of age. The most frequently drug classes used were analgesics 21 of 47 cases and antidepressants 11 of 47 cases. Risk factors were parents' divorce and family dysfunction in 16 of 47 cases of the population. Suicidal behavior in children and adolescents can be a way to attract attention, as well as an alarm signal asking for help. Analgesics and antidepressants are drugs commonly used in suicide attempts.

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.

Bioavailability of an extemporaneous suspension of propafenone made from tablets.

Propafenone is an effective antiarrhythmic agent used in children, while in Mexico no specific formulation for children is available, which causes errors in adequate dosage. The aim of this study was to determine the bioavailability of a suspension prepared extemporaneously using commercial tablets of propafenone. The bioavailability was determined in two groups of rabbits (n = 8): the first group received a single intravenous dose of 2 mg/kg of propafenone; the second was orally administered an extemporaneous suspension of propafenone prepared from commercial tablets. Blood samples were drawn at several times during the next 24 h and analysed by HPLC to determine drug levels. The extemporaneous suspension was tested previously with satisfactory results regarding physicochemical and microbiologic stability. The area under the curve (AUC) for the i.v. route was 5600.6 ng/ml.h and for oral administration the AUC was 3327.6 ng/ml.h. The bioavailability was calculated at 59.41%. These results are consistent with previous reports for solid dosage forms. The propafenone suspension prepared extemporaneously using commercial tablets is bioavailable using an animal model; nevertheless, it is necessary to carry out human studies either in volunteers or in patients to confirm these results.