Browsing by Author "Greenberg, Rachel G."

Now showing 1 - 2 of 2
  • Thumbnail Image
    Item
    Opportunistic dried blood spot sampling validates and optimizes a pediatric population pharmacokinetic model of metronidazole
    (American Society for Microbiology, 2024) Randell, Rachel L.; Balevic, Stephen J.; Greenberg, Rachel G.; Cohen-Wolkowiez, Michael; Thompson, Elizabeth J.; Venkatachalam, Saranya; Smith, Michael J.; Bendel, Catherine; Bliss, Joseph M.; Chaaban, Hala; Chhabra, Rakesh; Dammann, Christiane E. L.; Downey, L. Corbin; Hornik, Chi; Hussain, Naveed; Laughon, Matthew M.; Lavery, Adrian; Moya, Fernando; Saxonhouse, Matthew; Sokol, Gregory M.; Trembath, Andrea; Weitkamp, Joern-Hendrik; Hornik, Christoph P.; Best Pharmaceuticals for Children Act – Pediatric Trials Network Steering Committee; Pediatrics, School of Medicine
    Pharmacokinetic models rarely undergo external validation in vulnerable populations such as critically ill infants, thereby limiting the accuracy, efficacy, and safety of model-informed dosing in real-world settings. Here, we describe an opportunistic approach using dried blood spots (DBS) to evaluate a population pharmacokinetic model of metronidazole in critically ill preterm infants of gestational age (GA) ≤31 weeks from the Metronidazole Pharmacokinetics in Premature Infants (PTN_METRO, NCT01222585) study. First, we used linear correlation to compare 42 paired DBS and plasma metronidazole concentrations from 21 preterm infants [mean (SD): post natal age 28.0 (21.7) days, GA 26.3 (2.4) weeks]. Using the resulting predictive equation, we estimated plasma metronidazole concentrations (ePlasma) from 399 DBS collected from 122 preterm and term infants [mean (SD): post natal age 16.7 (15.8) days, GA 31.4 (5.1) weeks] from the Antibiotic Safety in Infants with Complicated Intra-Abdominal Infections (SCAMP, NCT01994993) trial. When evaluating the PTN_METRO model using ePlasma from the SCAMP trial, we found that the model generally predicted ePlasma well in preterm infants with GA ≤31 weeks. When including ePlasma from term and preterm infants with GA >31 weeks, the model was optimized using a sigmoidal Emax maturation function of postmenstrual age on clearance and estimated the exponent of weight on volume of distribution. The optimized model supports existing dosing guidelines and adds new data to support a 6-hour dosing interval for infants with postmenstrual age >40 weeks. Using an opportunistic DBS to externally validate and optimize a metronidazole population pharmacokinetic model was feasible and useful in this vulnerable population.
  • Thumbnail Image
    Item
    Urine Gastrin Releasing Peptide in the First Week Correlates with BPD and Post-Prematurity Respiratory Disease
    (Wiley, 2020-04) Voynow, Judith A.; Fisher, Kimberley; Sunday, Mary E.; Cotton, C. Michael; Hamvas, Aaron; Hendricks-Muñoz, Karen D.; Poindexter, Brenda B.; Pryhuber, Gloria S.; Ren, Clement L.; Ryan, Rita M.; Sharp, Jack K.; Young, Sarah P.; Zhang, Haoyue; Greenberg, Rachel G.; Herring, Amy H.; Davis, Stephanie D.; Pediatrics, School of Medicine
    Rationale: Bronchopulmonary dysplasia (BPD) is associated with post-prematurity respiratory disease (PRD) in survivors of extreme preterm birth. Identifying early biomarkers that correlate with later development of BPD and PRD may provide insights for intervention. In a preterm baboon model, elevated gastrin-releasing peptide (GRP) is associated with BPD, and GRP inhibition mitigates BPD occurrence. Objective: We performed a prospective cohort study to investigate whether urine GRP levels obtained in the first postnatal week were associated with BPD, PRD, and other urinary biomarkers of oxidative stress. Methods: Extremely low gestational age infants (23-28 completed weeks) were enrolled in a US multicenter observational study, The Prematurity and Respiratory Outcomes Program (http://clinicaltrials.gov/ct2/show/NCT01435187). We used multivariable logistic regression to examine the association between urine GRP in the first postnatal week and multiple respiratory outcomes: BPD, defined as supplemental oxygen use at 36 + 0 weeks postmenstrual age, and post-PRD, defined by positive quarterly surveys for increased medical utilization over the first year (PRD score). Results: A total of 109 of 257 (42%) infants had BPD, and 120 of 217 (55%) had PRD. On adjusted analysis, GRP level more than 80 was associated with BPD (adjusted odds ratio [aOR], 1.83; 95% confidence interval [CI], 1.03-3.25) and positive PRD score (aOR, 2.46; 95% CI, 1.35-4.48). Urine GRP levels correlated with duration of NICU ventilatory and oxygen support and with biomarkers of oxidative stress: allantoin and 8-hydroxydeoxyguanosine. Conclusions: Urine GRP in the first postnatal week was associated with concurrent urine biomarkers of oxidative stress and with later diagnoses of BPD and PRD.