Enantiomer‐selective pharmacokinetics and metabolism of ketorolac in children

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/110020/1/cptclpt1999381.pd

Pharmacokinetics and pharmacodynamics of famotidine and ranitidine in critically ill children

To characterize and compare acid suppression (pharmacodynamics) and pharmacokinetics of IV famotidine and ranitidine in critically ill children at risk for stress gastritis. Single‐blind, randomized study in PICU patients 6 months to 18 years requiring mechanical ventilation with continuous gastric pH monitoring, randomized to IV famotidine 12 mg/m 2 or ranitidine 60 mg/m 2 when gastric pH 1 hour with serial blood sampling following first dose. Twenty‐four children randomized to either famotidine (n = 12) or ranitidine (n = 12). Sixteen out of twenty‐four completed both PK and PD study arms (7/12 famotidine; 4.7 ± 3.4 years; 9/12 ranitidine; 6.6 ± 4.7 years; p  = 0.38). Time to gastric pH 4.0 and total time pH above 4.0 similar with no difference in pH at 6 and 12 hours ( p  > 0.2). No difference between drugs in clearance, volume of distribution and half‐life ( p  > 0.05). Ratio of AUC pH to AUC drug concentration 0–12 hours after first dose was significantly greater for famotidine (0.06849 ± 0.01460 SD) than ranitidine (0.02453 ± 0.01448; p  < 0.001) demonstrating greater potency of famotidine. pH lowering efficacy of both drugs is similar. Greater potency of famotidine may offer clinical advantage due to lower drug exposure and less frequent dosing to achieve same pH lowering effect.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/102678/1/jcph219.pd

Reversal of methylprednisolone effects in allergen-exposed female BALB/c mice

A high percentage of asthma is associated with aeroallergen exposures. Glucocorticoids such as methylprednisolone represent a major method for managing chronic asthma. However, studies suggested that corticosteroid therapy might have the potential to stimulate rather than inhibit adaptive immune inflammatory reactions, raising concerns about possible adverse reactions due to excessive repeated methylprednisolone treatment. Therefore, a murine model of allergen-induced inflammation was characterized and used to investigate the effects of repeated intraperitoneal (ip) and transnasal treatments with methylprednisolone (0-20 mg/kg body weight) and cyclosporin A (20 mg/kg body weight). Sensitized BALB/c female mice were exposed daily to ovalbumin (OVA) aerosols for up to 5 d with 24-h postexposure analyses for airway responses to methacholine aerosols and inflammatory cell recoveries by bronchoalveolar lavage (BAL) and tissue collagenase dispersion. Although increased tissue neutrophils, lymphocytes, monocytes, and macrophages reached maximal levels after 2 daily OVA exposures, recoverable eosinophil numbers continued to rise over the 5-d period. Daily ip treatments with a 5-mg/kg body weight dose of methylprednisolone diminished both OVA-induced airway responses to methacholine and inflammatory-cell accumulations to levels comparable to those observed with cyclosporin A. However, treatments with higher doses of methylprednisolone reversed this anti-inflammatory effect, indicated by a return to untreated levels of OVA-induced eosinophil recovery. A similar biphasic response in eosinophil recoveries was observed using daily transnasal methylprednisolone treatments that correlated with a concomitant fall and rise in BAL interleukin-13. These results supported the hypothesis that repeated high-steroid treatments might activate rather than suppress allergen-induced immune responses

The Collaborative Role of North American Departments of Pediatrics in Global Child Health

Appeals for health equity call for departments of pediatrics to improve the health of all children including those from underserved communities in North America and around the world. Consequently, North American (NA) departments of pediatrics have a role in global child health (GCH) which focuses on providing health care to underserved children worldwide. In this review, we describe how NA departments of pediatrics can collaboratively engage in GCH education, clinical practice, research, and advocacy and summarize best practices, challenges, and next steps for engaging in GCH in each of these areas. For GCH in low- and middle-income countries (LMICs), best practices start with the establishment of ethical, equitable, and collaborative partnerships with LMIC communities, organizations, and institutions engaged in GCH who are responsible for the vast majority of work done in GCH. Other best practices include adequate preparation of trainees and clinicians for GCH experiences; alignment with local clinical and research priorities; contributions to local professional development and ongoing monitoring and evaluation. Challenges for departments include generating funding for GCH activities; recruitment and retention of GCH-focused faculty members; and challenges meeting best practices, particularly adequate preparation of trainees and clinicians and ensuring mutual benefit and reciprocity in NA–LMIC collaborations. We provide examples of how departments have overcome these challenges and suggest next steps for development of the role of NA departments of pediatrics in GCH. Collaborative implementation of best practices in GCH by LMIC–NA partnerships can contribute to reductions of child mortality and morbidity globally