Clinical Therapeutics • September 2016
Zimmerman K, Putera M, Hornik CP, Smith PB, Benjamin DK Jr, Mulugeta Y, Burckart GJ, Cohen-Wolkowiez M, Gonzalez D
We sought to determine the extent of exposure matching, defined by a comparison of area under the concentration-time curve, between children and adults, for anti-infective drug products submitted to the FDA for approval.
Antimicrobial Agents and Chemotherapy • August 2016
Momper JD, Capparelli EV, Wade KC, Kantak A, Dhanireddy R, Cummings JJ, Nedrelow JH, Hudak ML, Mundakel GT, Natarajan G, Gao J, Laughon M, Smith PB, Benjamin DK Jr.
Fluconazole is an effective agent for prophylaxis of invasive candidiasis in premature infants. The objective of this study was to characterize the population pharmacokinetics (PK) and dosing requirements of fluconazole in infants with birth weights of <750 g. As part of a randomized clinical trial, infants born at <750 g birth weight received intravenous (i.v.) or oral fluconazole at 6 mg/kg of body weight twice weekly.
Clinical Infectious Diseases • August 2016
Ericson JE, Kaufman DA, Kicklighter SD, Bhatia J, Testoni D, Gao J, Smith PB, Prather KO, Benjamin DK Jr; Fluconazole Prophylaxis Study Team on behalf of the Best Pharmaceuticals for Children Act–Pediatric Trials Network Steering Committee.
Invasive candidiasis (IC) is an important cause of sepsis in premature infants and is associated with a high risk of death and neurodevelopmental impairment. Prevention of IC has become a major focus in very low birth weight infants, with fluconazole increasingly used as prophylaxis. We identified all randomized, placebo-controlled trials evaluating fluconazole prophylaxis in premature infants conducted in the United States.
Journal of Pediatrics • August 2016
Hornik CP, Benjamin DK Jr, Smith PB, Pencina MJ, Tremoulet AH, Capparelli EV, Ericson JE, Clark RH, Cohen-Wolkowiez M; Best Pharmaceuticals for Children Act—Pediatric Trials Network.
This was a retrospective observational cohort study of electronic health record (EHR) data combined with pharmacokinetic model derived drug exposure predictions. We used the EHR from 348 Pediatrix Medical Group neonatal intensive care units from 1997 to 2012. We included all infants 24-41 weeks gestational age, 500-5400 g birth weight, first exposed to ampicillin prior to 25 days postnatal age. In this cohort of hospitalized infants, higher ampicillin exposure was associated with seizures as documented in the EHR.
JAMA Pediatrics • August 2016
Early Human Development • August 2016
Romaine A, Ye D, Ao Z, Fang F, Johnson O, Blake T, Benjamin DK Jr, Cotten CM, Testoni D, Clark RH, Chu VH, Smith PB, Hornik CP; Best Pharmaceuticals for Children Act – Pediatric Trials Network.
Histamine-2 receptor (H2) blockers are often used in very low birth weight infants despite lack of population specific efficacy and safety data. We sought to describe safety and temporal trends in histamine-2 receptor (H2) blocker use in hospitalized very low birth weight (VLBW) infants.
Antimicrobial Agents and Chemotherapy • April 2016
Gonzalez D, Delmore P, Bloom BT, Cotten CM, Poindexter BB, McGowan E, Shattuck K, Bradford KK, Smith PB, Cohen-Wolkowiez M, Morris M, Yin W, Benjamin DK Jr, Laughon MM.
Clindamycin may be active against methicillin-resistant Staphylococcus aureus, a common pathogen causing sepsis in infants, but optimal dosing in this population is unknown. We performed a multicenter, prospective pharmacokinetic (PK) and safety study of clindamycin in infants. We analyzed the data using a population PK analysis approach and included samples from two additional pediatric trials.
Contemporary Clinical Trials • March 2016
England A, Wade K, Smith PB, Berezny K, Laughon M; Best Pharmaceuticals for Children Act — Pediatric Trials Network Administrative Core Committee.
Performing drug trials in pediatrics is challenging. In support of the Best Pharmaceuticals for Children Act, the Eunice Kennedy Shriver National Institute of Child Health and Human Development funded the formation of the Pediatric Trials Network (PTN) in 2010. Since its inception, the PTN has developed strategies to increase both efficiency and safety of pediatric drug trials. Through use of innovative techniques such as sparse and scavenged blood sampling as well as opportunistic study design, participation in trials has grown. The PTN has also strived to improve consistency of adverse event reporting in neonatal drug trials through the development of a standardized adverse event table. We review how the PTN is optimizing operational efficiencies in pediatric drug trials to increase the safety of drugs in children.
American Journal of Perinatology • March 2016
Lee JH, Hornik CP, Testoni D, Laughon MM, Cotton CM, Maldonado RS, Belcastro MR, Clark RH, Smith PB
The Journal of Clinical Pharmacology • March 2016
Estepp JH, Melloni C, Thornburg CD, Wiczling P, Rogers Z, Rothman JA, Green NS, Liem R, Brandow AM, Crary SE, Howard TH, Morris MH, Lewandowski A, Garg U, Jusko WJ, Neville KA; Best Pharmaceuticals for Children Act-Pediatric Trials Network Administrative Core Committee.
Hydroxyurea (HU) is a crucial therapy for children with sickle cell anemia, but its off-label use is a barrier to widespread acceptance. We found HU exposure is not significantly altered by liquid vs capsule formulation, and weight-based dosing schemes provide consistent exposure. HU is recommended for all children starting as young as 9 months of age with sickle cell anemia; however; a paucity of pediatric data exists regarding the pharmacokinetics (PK) or the exposure-response relationship of HU.
