This Pharmacometrics (PM) Core (B) supports the program entitled "Developmental and Translational Pharmacology of Pediatric Antimicrobial Therapy", submitted as an application responsive to RFA-HD-10-026: Specialized Center in Research in Pediatric Developmental Pharmacology (RPDP) Program (U54). The overall theme of the proposed program at UC San Diego is to bring together non-clinical and clinical experts in the fields of developmental physiology, pharmacology, and infectious diseases and conduct translational research to advance the field of pediatric developmental pharmacology. The PM Core will leverage existing PK/PD modeling expertise and processes at UC San Diego and support pharmacokinetic /pharmacodynamic and dynamic disease analyses for all three Projects and the current two Pilot Projects. It will utilize state-of-the-art population and physiologic based approaches that incorporate maturation models of drug disposition and will ultimately lead to Improved maturation models. In direct support of the Projects, this Core will construct population pharmacokinetic models for colistimethate and colistin that incorporate developmental changes and utilize both plasma and urine drug concentrations. Monte Carlo simulations will be employed to help develop age appropriate colistimethate dosing. The PM Core will also develop endogenous production models for cathelicidin generation in response to infection and quantify in vitro interactions with pharmaceutical antibiotics. Ultimately we will link cathelicidin generation models with physiologic-based pharmacokinetic (PBPK) models of pharmaceutical antibiotics to assess drug-drug interactions at potential infection sites. Finally the pharmacometrics core will develop new pharmacokinetic models for aminopenicillins in rats and extend current population pharmacokinetic models of aminopenicillins in infants to older children characterizing urinary excretion. This will lead to a better understanding of the functional development of the Oat system and drug dosing implications for Oat substrates. The PM Core will interact with the Quantitative Pharmacology Assay Core to set assay sensitivity requirements and will play a pivotal role in assisting the Training &Outreach Core.

Public Health Relevance

Model based approaches to describing developmental drug disposition and effects play a critical role in understanding the mechanisms of antimicrobial therapy. Linked with simulations, these models can increase the knowledge generated from the RPDP Center's Projects and help translate the results into age appropriate dosing and therapy.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Specialized Center--Cooperative Agreements (U54)
Project #
Application #
Study Section
Special Emphasis Panel (ZHD1-DSR-A)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of California San Diego
La Jolla
United States
Zip Code
Sampson, Mario R; Frymoyer, Adam; Rattray, Benjamin et al. (2014) Predictive performance of a gentamicin population pharmacokinetic model in neonates receiving full-body hypothermia. Ther Drug Monit 36:584-9
Tremoulet, Adriana; Le, Jennifer; Poindexter, Brenda et al. (2014) Characterization of the population pharmacokinetics of ampicillin in neonates using an opportunistic study design. Antimicrob Agents Chemother 58:3013-20
Sinko, William; Wang, Yang; Zhu, Wei et al. (2014) Undecaprenyl diphosphate synthase inhibitors: antibacterial drug leads. J Med Chem 57:5693-701
Le, Jennifer; Ngu, Becky; Bradley, John S et al. (2014) Vancomycin monitoring in children using bayesian estimation. Ther Drug Monit 36:510-8
Gonzalez, David J; Vuong, Lisa; Gonzalez, Isaiah S et al. (2014) Phenol soluble modulin (PSM) variants of community-associated methicillin-resistant Staphylococcus aureus (MRSA) captured using mass spectrometry-based molecular networking. Mol Cell Proteomics 13:1262-72
Sakoulas, George; Rose, Warren; Nonejuie, Poochit et al. (2014) Ceftaroline restores daptomycin activity against daptomycin-nonsusceptible vancomycin-resistant Enterococcus faecium. Antimicrob Agents Chemother 58:1494-500
Autmizguine, Julie; Moran, Cassie; Gonzalez, Daniel et al. (2014) Vancomycin cerebrospinal fluid pharmacokinetics in children with cerebral ventricular shunt infections. Pediatr Infect Dis J 33:e270-2
Sakoulas, George; Okumura, Cheryl Y; Thienphrapa, Wdee et al. (2014) Nafcillin enhances innate immune-mediated killing of methicillin-resistant Staphylococcus aureus. J Mol Med (Berl) 92:139-49
Bayer, Arnold S; Mishra, Nagendra N; Sakoulas, George et al. (2014) Heterogeneity of mprF sequences in methicillin-resistant Staphylococcus aureus clinical isolates: role in cross-resistance between daptomycin and host defense antimicrobial peptides. Antimicrob Agents Chemother 58:7462-7
Liu, Yan; Haste, Nina M; Thienphrapa, Wdee et al. (2014) Marinopyrrole derivatives as potential antibiotic agents against methicillin-resistant Staphylococcus aureus (III). Mar Drugs 12:2458-70

Showing the most recent 10 out of 24 publications