Farmacocinética de posaconazol en la profilaxis y tratamiento de la infección fúngica invasora en niños inmunocomprometidos en un hospital pediátrico / Pharmacokinetics of posaconazol in the prophylaxis and treatment of invasive fungal infection in immunocompromised children in a pediatric hospital

Resumen Introducción En pediatría no existe consenso en la dosificación de posaconazol (PSC) para profilaxis y tratamiento de la infección fúngica invasora (IFI), usándose la medición de concentraciones plasmáticas (CPs) del fármaco. Objetivo Describir la experiencia de monitoreo de las CPs de PSC en niños inmunocomprometidos con IFI y determinar si las dosis recomendadas alcanzan CPs efectivas en profilaxis (≥ 0,7 µg/mL) y tratamiento (≥ 1,25 µg/mL). Método Análisis retrospectivo en niños que recibieron PSC suspensión como profilaxis o tratamiento entre enero de 2012 y octubre de 2016, en las unidades de Oncología y Trasplante de Médula Ósea del Hospital Calvo Mackenna. Resultados 78 CPs en seis pacientes (4 indicaciones de profilaxis y 4 tratamientos) fueron revisados. La mediana de dosis de PSC fue de 12,5 y 18,8 mg/kg/d para profilaxis y tratamiento, respectivamente, resultando CP mediana de 0,97 y 1,8 μg/mL, respectivamente. En profilaxis, se registraron 40/67 (60%) con CP ≥ 0,70 μg/mL recibiendo una mediana de dosis de 12,5 mg/kg/d. Mientras que para el tratamiento: 5/11 (46%), presentaron CP ≥ 1,25 μg/mL, recibiendo una mediana de dosis de 18 mg/kg/d. Conclusión Nuestros resultados se ajustan a lo recomendado para la dosificación de PSC, pero evidencian una necesidad de realizar una monitorización individualizada para mantener adecuadas CPs.

Background There is no consensus on the optimal dosage use of posaconazole (PSC) for invasive fungal infection (IFI) in pediatric patients and normally it is adjusted with drug levels (DLs) ≥ 0.7 μg/ml and ≥ 1.25 μg/ml for prophylaxis and treatment, respectively. Objective To describe the experience of monitoring DLs of PSC in immunocompromised pediatric patients with IFI and to determine if the recommended doses reach CP effective in prophylaxis (≥ 0.7 μg/mL) and treatment (≥ 1.25 μg/mL). Method A retrospective analysis in children who received PSC from January 2012 to October 2016, in the Oncology and Bone Marrow Transplant units at Hospital Calvo Mackenna was done Six patients with 78 DLs were reviewed (4 prophylaxis and 4 treatment). Median PSC dose was 12.5 and 18.8 mg/kg/d for prophylaxis and treatment, resulting in mean DLs of 0.97 and 1.8 μg/mL respectively. In prophylaxis 40/67 (60%) were recorded with DLs ≥ 0.70 μg/mL receiving a median dose of 12.5 mg/kg/d. While for treatment: 5/11 (46%) presented DLs ≥ 1.25 μg/mL, receiving a median dose of 18 mg/kg/d. Conclusion Our results are in line with the recommended for PSC dosage, but individualized monitoring is required to maintain adequate DLs.

Serum Phenobarbitone Levels in Term and Near-Term Neonates with Seizures.

Objective: To evaluate serum phenobarbitone levels in neonates with seizures and to evaluate the effect of repeated loading dose on serum phenobarbitone levels. Methods: In this prospective observational study conducted in a tertiary care centre of Northern India during 2011- 2012, 99 neonates admitted with seizureswere included.Serum phenobarbitone levels in neonates with seizures at 20 minutes and 12 hours after the first loading dose of phenobarbitone were measured. Results: Serum phenobarbitone levels [mean (SD)] at 20 min and 12 hours was 27.3 (28.4) µg/mL and 23 (19.1) µg/mL, respectively (P=0.07). The mean serum phenobarbitone levels 12 hours after the loading dose, and proportion of neonates with toxic levels increased with each loading dose of intravenous phenobarbitone. Conclusion: Monitoring of serum level of phonobarbitone may not be essential because seizure control in neonates appears to be independent of whether serum level is subtherapeutic, therapeutic or toxic range.

Serum Nevirapine and Efavirenz Concentrations and Effect of Concomitant Rifampicin in HIV Infected Children on Antiretroviral Therapy.

Objective: To determine factors affecting serum levels of Efavirenz and Nevirapine and analyze the effect of Rifampicin on Nevirapine drug levels. Methods: A cross-sectional study was conducted on 30 HIV infected children on Antiretroviral therapy (ART) with Nevirapine or Efavirenz. Patients on simultaneous Rifampicin and Nevirapine were given higher doses of Nevirapine with regular monitoring of liver function tests. Trough levels (before morning dose of Nevirapine) and levels after 2 hours of administration of Nevirapine and levels of Efavirenz were assessed using HPLC and were checked to see if they fall within the therapeutic range. Results: Thirty patients (14 males) were enrolled in the study with 20 on Nevirapine and 10 (33.3%) on Efavirenz. Seven (23.3%) patients were simultaneously taking rifampicin. The mean Nevirapine dose given to the patients was 350.9±59.8mg/m2/day (on simultaneous rifampicin) and 309.2±54.6mg/m2/day (not on concurrent rifampicin). Thirteen (81.3%) of the 16 patients with trough Nevirapine had values in the normal range, 1 (6.3%) had low Nevirapine trough levels and 2 (12.5%) had high Nevirapine trough levels. Of the post 2 hours Nevirapine levels, 1 (5%) had low levels and 3 (15%) had high Nevirapine blood levels. Factors like age (P=0.4, P=0.4087), nourishment (P=0.2679, P=0.4132), ART combination (P=0.4199, P=0.4132), form of the drug (tablet/syrup) (P=0.1964, P=0.4696) or if it was being given as single or in a fixed dose combination (P=0.4179, P=0.4696) and even concurrent rifampicin administration (P=0.284, P=0.472) did not significantly affect the trough and post 2 hours Nevirapine values, respectively. All the five patients being given concurrent rifampicin had normal trough and post 2 hours levels of Nevirapine. The Efavirenz drug levels were 1.9±1.1 g/mL. Of the 10 patients on Efavirenz, 2 (20%) had high and 1 (10%) had low blood levels. Conclusion: Concurrent Rifampicin administration does not alter blood levels of Nevirapine; provided the dose of Nevirapine is increased by 20-30%. Formulation of drugs does not alter the blood levels provided drug administered is in the recommended dose.

Study on the pharmacokinetics of alprazolam at different dose in rats / 中国药理学通报

The pharmacokinetics of alprazolam in 18 rats was studied by using reversed-phase HPLC. The pharmacokinetic characteristics were fit to one compartment opened model after intragastric administration of alprazolam at doses of 50,20 and 2 mg ? kg-1, respectively. The absorbing and eliminating parameters between the three groups were no significant difference. Mean of Ka was 3. 3454 h-1,Ke 0. 3873h-1,T1/2Ka 0. 29 h, T1/2Ke 2.61 h, and Tmax 1.04 h. There was a positiverelationship between the serum concentration and dosage (r = 0. 6096, P