The Risk of Nonsteroidal Anti-Inflammatory Drugs in Pediatric Medicine: Listen Carefully to Children with Pain

Over the last decades, the use of over-the-counter analgesics in the general population has increased in Germany. Ibuprofen is one of the most commonly used nonsteroidal anti-inflammatory drug (NSAID) and is frequently prescribed to children as an analgesic and/or antipyretic. Besides having a well-established safety and efficacy profile when used in appropriate doses, cases of NSAID-induced acute kidney injury (AKI) have been described in the pediatric population, particularly in the context of dehydration and in combination with other drugs. The ingestion of more than 400 mg/kg is associated with severe or life-threatening toxicity. This report is about two previously healthy adolescents, who developed AKI after taking high daily dose of ibuprofen as a pain reliever without any appropriate medical supervision. With these case reports, in addition to the side effect profiles of this analgesic, we would also like to present a certain therapeutic recommendation that we applied in these patients, and furthermore appeal to pediatricians to strictly set the indications for ibuprofen intake.

Elemental Composition of Algae-Based Supplements by Energy Dispersive X-ray Fluorescence

The aim of this study is to evaluate the elemental composition of fifteen algae-based supplements commonly sold in the Portuguese market, by energy dispersive X-ray fluorescence. Despite the fact that the majority of Kelp samples were a good source of iodine, the levels observed might well contribute to an excess in the human body, which can cause dysfunction of the thyroid gland. Furthermore, the presence of lead in Sea spaghetti, Arame, Hijiki and Wakame caused a considerable risk to public health vis a vis possible ingestion of a high daily dose. Regarding arsenic, great variability was observed in all the samples with concentrations equal to or above 60 μg/g in the case of Arame, KelpJ and Hijiki. Although algae mainly accumulate organic arsenic, some also contain high levels of its inorganic form, as is commonly pointed out for Hijiki. Thus, regular ingestion of these supplements must also take into account the mentioned facts. There is no doubt that these supplements are also good sources of other nutrients, but the lack of accurate regulations and control should alert consumers to avoid indiscriminate use of these types of products.

Gefapixant in two randomised dose-escalation studies in chronic cough

Background and objectivesGefapixant has previously demonstrated efficacy in the treatment of refractory chronic cough at a high daily dose. The current investigations explore efficacy and tolerability of gefapixant, a P2X3 receptor antagonist, for the treatment of chronic cough using a dose-escalation approach.Materials and methodsTwo randomised, double-blind, placebo-controlled, crossover, dose-escalation studies recruited participants with refractory chronic cough. Patients were assigned to receive ascending doses of gefapixant (study 1: 50–200 mg, study 2: 7.5–50 mg) or placebo for 16 days, then crossed-over after washout. The primary end-point was awake cough frequency assessed using a 24-h ambulatory cough monitor at baseline and on day 4 of each dose. Patient-reported outcomes included a cough severity visual analogue scale and the cough severity diary.ResultsIn clinical studies, gefapixant doses ≥30 mg produced maximal improvements in cough frequency compared with placebo (p<0.05); reported cough severity measures improved at similar doses. Taste disturbance exhibited a different relationship with dose, apparently maximal at doses ≥150 mg.ConclusionsP2X3 antagonism with gefapixant demonstrates anti-tussive efficacy and improved tolerability at lower doses than previously investigated. Studies of longer duration are warranted.

962. Cutaneous Leishmaniasis: Investigating Skin Drug Levels to Optimize Liposomal Amphotericin Dosing

Background Liposomal amphotericin B (L-amB, AmBisome®) is popular for off-label use in the treatment of cutaneous leishmaniasis (CL) using dosing of 3 mg/kg/day for days 1–5, 8, 9, or days 1–5, 10 with reported clinical cure rates of 46–84%. In rodents, the skin concentration of L-amB is 40-fold less than that in visceral organs. We hypothesize that a specific L-amB regimen targeted to skin concentrations could maximize a beneficial treatment response in CL. Methods SKH1 477 Elite hairless mice (Charles River), 5 per group, received intravenous L-amB at doses of (A) 3 mg/kg/day for days 1–5, 8, 9, (B) 5 mg/kg/day for 4 days, (C) 10 mg/kg load than 5 mg/kg/day for 3 days, (D)10 mg/kg/day for 2 days, (E) 15 mg/kg/day for 2 days. Serum and skin (back) punch biopsies were collected on day 0, 2, 5, 14, and 21. Nasal mucosa was biopsied on day 21. Tissue samples were homogenized and L-amB was extracted with methanol and acetonitrile. Liquid chromatography–mass spectrometry was performed using these extracted samples on an Agilent 1200 series HPLC and an AB Sciex Q-Trap 4000 mass spectrometer. Experiment conducted twice for confirmation. Results L-amB doses were well tolerated by the mice, except weight loss was seen in regimen E. Day 21 serum L-amB levels were 82 ± 3.2 (ng/mL) regimen A, 91 ± 4.2 in B, 89 ± 4 in C, 118 ± 3.7 in D, 98 ± 1.5 in E. Mean L-amB nasal tissue levels on day 21 were 1.33 + 3.2 (ng/mg tissue) regimen A and 6.5 ± 3 in D (P = 0.031). Mean L-amb skin levels on day 14 were 8.4 ± 5.6 (ng/mg tissue) in regimen A, 4.0 ± 1.7 in B, 6.2 ± 3.3 in C, 13.9 ± 7.1 in D, 33.9 ± 24.7 in E. Skin L-amB levels at day 21 were less than 5 (ng/mg tissue) except for regimen D 9.3 ± 4.2 and regimen E 7.8 ± 2.6. SKH1 477 Elite mice did not permit an adequate Leishmania major infection (very tiny lesions when compared with other murine species) to correlate these results clinically in this specific murine model. Conclusion While regimens A–D received similar total dosages of L-amB, the skin and nasal mucosal levels were significantly higher in the short, high daily dose regimens compared with the L-amB regimen that is currently used in CL patients. This suggests that better clinical results might be seen by using a L-amB dosing regimen for CL of 10 mg/kg for 2 days, a dose regularly used in the treatment of pediatric visceral leishmaniasis. Disclosures All authors: No reported disclosures.