The candidate is a neonatologist with strong training in epidemiology and a proven commitment to the study of patient-oriented research, with a desire to develop clinical pharmacology skills. The candidate's long-term career goal is to advance public health by improving drug safety and dosing in infants. The candidate's short- term career goals for the K23 program are to: 1) acquire knowledge and skills in clinical pharmacology;2) develop the professional skills to successfully lead a PK/PD clinical trial research team;and 3) produce a critical mass of preliminary data and publications to support an R01 grant application and establish a program of independent research in clinical pharmacology. The proposed research plan, career development activities, mentorship team, and institutional environment are all uniquely suited to assist the applicant in achieving these goals. Although antibiotics are the most commonly used medications in hospitalized infants, dosing for infants is often extrapolated from data obtained in older children and adults. Fluconazole and rifampin are two antimicrobials commonly used in the nursery for which pharmacokinetic data can be improved. Dr. Laughon will use an integrative approach to investigate the pharmacokinetics and pharmacodynamics of these two agents in premature infants. This approach will include: application of sparse sampling methodologies;population PK/PD modeling;development of dried blood spot technology;a dual center PK trial;and a multi- site PK trial. This proposal will capitalize on unique opportunities provided by the Fluconazole Prophylaxis trial (PI: Benjamin, mentor), the NICHD PPRU open label fluconazole trial, and the Duke fluconazole trial. Dr. Laughon will also have access to the resources of the Duke Clinical Research Institute (Benjamin) and the Eshelman School of Pharmacy at UNC (Brouwer, co-mentor). To support the candidate's career development, he will participate in the UNC/Duke clinical pharmacology fellowship and become board certified in clinical pharmacology. The mentorship team assembled is uniquely qualified, and strengths include extensive clinical research experience;internationally recognized thought leadership in trial design, research methods, pharmacology, and PK/PD modeling;and a successful history of mentorship of junior faculty. Dr. Laughon's K23 proposal will provide him with the opportunity to learn PK/PD modeling and simulation techniques and to develop a dried blood spot assay in addition to refining clinical trial methodologies to maximize information gained from the limited samples available in this vulnerable population. The research environment including the Translational and Clinical Sciences Institute at UNC and the DCRI at Duke provide a productive, collegial, and collaborative atmosphere in which to pursue the above research and training goals. At the conclusion of this program, Dr. Laughon will be positioned to be an independent physician-scientist leading a research team.
Invasive infections in premature infants are common and often fatal. Therefore, physicians commonly prescribe antimicrobial agents to treat suspected or confirmed infections in this population. Appropriate dosing of most antimicrobial agents in infants is unknown and information obtained from older patients has failed to accurately predict newborn drug disposition. This proposal will use a novel approach to investigate the pharmacokinetics (PK) and pharmacodynamics (PD) of antimicrobial agents commonly used in infants, using scavenge sampling methodologies, advanced PK-PD modeling, and dried blood spot technology.
| Thompson, Elizabeth J; Greenberg, Rachel G; Kumar, Karan et al. (2018) Association between Furosemide Exposure and Patent Ductus Arteriosus in Hospitalized Infants of Very Low Birth Weight. J Pediatr 199:231-236 |
| Hornik, Christoph P; Onufrak, Nikolas J; Smith, P Brian et al. (2018) Association between oral sildenafil dosing, predicted exposure, and systemic hypotension in hospitalised infants. Cardiol Young 28:85-92 |
| Zimmerman, Kanecia O; Smith, P Brian; Benjamin, Daniel K et al. (2017) Sedation, Analgesia, and Paralysis during Mechanical Ventilation of Premature Infants. J Pediatr 180:99-104.e1 |
| Downey, L C; Cotten, C M; Hornik, C P et al. (2017) Association of in utero magnesium exposure and spontaneous intestinal perforations in extremely low birth weight infants. J Perinatol 37:641-644 |
| Gonzalez, Daniel; Delmore, Paula; Bloom, Barry T et al. (2016) Clindamycin Pharmacokinetics and Safety in Preterm and Term Infants. Antimicrob Agents Chemother 60:2888-94 |
| Hornik, Christoph P; Sherwood, Ashley L; Cotten, C Michael et al. (2016) Daily mortality of infants born at less than 30weeks' gestation. Early Hum Dev 96:27-30 |
| Johnson, Jacob K; Laughon, Matthew M (2016) Antimicrobial Agent Dosing in Infants. Clin Ther 38:1948-60 |
| England, Amanda; Wade, Kelly; Smith, P Brian et al. (2016) Optimizing operational efficiencies in early phase trials: The Pediatric Trials Network experience. Contemp Clin Trials 47:376-82 |
| Lee, Jan Hau; Smith, P Brian; Quek, M Bin Huey et al. (2016) Risk Factors and In-Hospital Outcomes following Tracheostomy in Infants. J Pediatr 173:39-44.e1 |
| Momper, Jeremiah D; Capparelli, Edmund V; Wade, Kelly C et al. (2016) Population Pharmacokinetics of Fluconazole in Premature Infants with Birth Weights Less than 750 Grams. Antimicrob Agents Chemother 60:5539-45 |
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