Drug disposition

Association between Furosemide Exposure and Patent Ductus Arteriosus in Hospitalized Infants of Very Low Birth Weight

Posted on by Kayla Korzekwinski

The Journal of Pediatrics • August 2018

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Thompson EJ, Greenberg RG, Kumar K, Laughon M, Smith PB, Clark RH, Crowell A, Shaw L, Harrison L, Scales G, Bell N, Hornik CP

This study evaluated the association between furosemide exposure and patent ductus arteriosus (PDA) in a large, contemporary cohort of hospitalized infants with very low birth weight (VLBW). Furosemide exposure was not associated with increased odds of PDA treatment in hospitalized infants of VLBW. Further studies are needed to characterize the efficacy and safety of furosemide in premature infants.

Population Pharmacokinetics of Trimethoprim-Sulfamethoxazole in Infants and Children

Posted on by Kayla Korzekwinski

Antimicrobial Agents and Chemotherapy • December 2017

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Autmizguine J, Melloni C, Hornik CP, Dallefeld S, Harper B, Yogev R, Sullivan JE, Atz AM, Al-Uzri A, Mendley S, Poindexter B, Mitchell J, Lewandowski A, Delmore P, Cohen-Wolkowiez M, Gonzalez D; the Pediatric Trials Network Steering Committee.

Trimethoprim (TMP)-sulfamethoxazole (SMX) is used to treat various types of infections, including community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) and Pneumocystis jirovecii infections in children. Pharmacokinetic (PK) data for infants and children are limited, and the optimal dosing is not known. We performed a multicenter, prospective PK study of TMP-SMX in infants and children.

Population Pharmacokinetics of Dexmedetomidine in Infants

Posted on by Kayla Korzekwinski

Journal of Clinical Pharmacology • September 2017

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Greenberg RG, Wu H, Laughon M, Capparelli E, Rowe S, Zimmerman KO, Smith PB, Cohen-Wolkowiez M

Despite limited pharmacokinetic (PK) data, dexmedetomidine is increasingly being used off-label for sedation in infants. This study aimed to characterize the developmental PK changes of dexmedetomidine during infancy.

Respiratory Support for Very Low Birth Weight Infants Receiving Dexamethasone

Posted on by Kayla Korzekwinski

The Journal of Pediatrics • April 2017

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Virkud YV, Hornik CP, Benjamin DK, Laughon MM, Clark RH, Greenberg RG, Smith PB.

To assess how neonatal intensive care units followed the American Academy of Pediatrics guidelines for use of dexamethasone in preterm infants by evaluating respiratory support at the time of dexamethasone administration. This is an observational study of infants discharged from one of 290 neonatal intensive care units from 2003 to 2010. The cohort included very low birth weight (<1500 g birth weight) infants born at ≤32 weeks gestational age. The main outcome was respiratory support at time of exposure to dexamethasone.

Use of Reflux Medications in Premature Infants After Hospital Discharge

Posted on by Kayla Korzekwinski

Pediatrics • December 2016

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Smith PB

Medications are frequently used to treat gastroesophageal reflux (GER) in premature infants. However, diagnostic modalities for GER are poor and clinical diagnosis is highly variable. Despite the frequent use of GER medications in premature infants, short- or long-term benefits of GER medications in this population are undocumented. Studies in premature infants have failed to show a correlation between apnea, bradycardia, or respiratory symptoms typically thought to be due to GER. This study sought to fill these information gaps.

Pharmacologic studies in vulnerable populations – using the pediatric experience

Posted on by Kayla Korzekwinski

Seminars in Perinatology • November 2016

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Zimmerman K, Gonzalez D, Swamy GK, Cohen-Wolkowiez M
Historically, few data exist to guide dosing in children and pregnant women. Multiple barriers to inclusion of these vulnerable populations in clinical trials have led to this paucity of data. Given the similar barriers to drug research and development in pediatric and pregnant populations, the route toward success in children may serve as a model for the advancement of drug development and appropriate drug administration in pregnant women.

Therapeutic Drug Monitoring, Electronic Health Records, and Pharmacokinetic Modeling to Evaluate Sirolimus Drug Exposure-Response Relationships in Renal Transplant Patients

Posted on by Kayla Korzekwinski

Therapeutic Drug Monitoring • October 2016

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Zimmerman K, Wu H, Greenberg R, Hill K, Patel U, Ku L, Gonzalez D, Hornik C, Melloni C, Cohen-Wolkowiez M

Sirolimus, an immunosuppressive agent used in renal transplantation, can prevent allograft rejection. Identification of the therapeutic index (the ratio of minimum toxic concentration to minimum therapeutic concentration) for immunosuppresants is necessary to optimize the care of patients and set standards for bioequivalence evaluation of sirolimus products. However, the therapeutic index for sirolimus has been inconsistently defined. Use of therapeutic drug monitoring results and PK modeling permitted correlation of sirolimus concentrations with graft loss or rejection and decline in renal function.

Exposure Matching of Pediatric Anti-infective Drugs: Review of Drugs Submitted to the Food and Drug Administration for Pediatric Approval

Posted on by Kayla Korzekwinski

Clinical Therapeutics • September 2016

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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.

Insulin, Hyperglycemia, and Severe Retinopathy of Prematurity in Extremely Low-Birth-Weight Infants

Posted on by Kayla Korzekwinski

American Journal of Perinatology • March 2016

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Lee JH, Hornik CP, Testoni D, Laughon MM, Cotton CM, Maldonado RS, Belcastro MR, Clark RH, Smith PB

This study aimed to determine the association between hyperglycemia, insulin therapy, and severe retinopathy of prematurity (ROP) in extremely low-birth-weight (ELBW) infants. Hyperglycemia alone was not associated with severe ROP in ELBW infants. However, researchers did observe a possible trend between the use of insulin and severe ROP.

Sildenafil and retinopathy of prematurity risk in very low birth weight infants

Posted on by Kayla Korzekwinski

American Journal of Perinatology • February 2016

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Samiee-Zafarghandy S, van den Anker JN, Laughon MM, Clark RH, Smith PB, Hornik CP; Pharmaceuticals for Children Act – Pediatric Trials Network Administrative Core Committee.

We identified premature infants who were discharged from Pediatrix Medical Group neonatal intensive care units from 2003–2012 and who received an ophthalmologic exam. We matched each infant exposed to sildenafil prior to first eye exam to three non-exposed infants using propensity scoring to control for differences in baseline infant characteristics. We evaluated the association between sildenafil exposure and development of severe ROP using conditional logistic regression.