Edmund Capparelli - Research Interests
• Pediatric Clinical Pharmacology
• Pharmacometrics – Population Pharmacokinetic
Pharmacodynamic and Disease Modeling
• Emphasis Areas–
• Pediatric Infectious Diseases
• Antivirals
• Antibacterials
• Neonatal Therapeutics
• Anti-convulsants
Core Expertise –
Pediatric Pharmacology Laboratory
• Lab currently located in Hillcrest (CTF-B112)
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Quantitative assays using HPLC / LCMS / GCMS methodology
Emphasis on anti-infectives / CNS active agents
Various matrices – Plasma, DBS, CSF, urine, hair, protein binding
CLIA for real time / FDA submissions
• NIH Collaborative Programs
• Center for Research in Pediatric and Developmental Pharmacology Network
(RPDP) - U54 (NICHD)
• International Maternal Pediatric and Adolescent AIDS Clinical Trials Network
(IMPAACT) – Pediatric Pharmacology Laboratory (NIAID)
• Pediatric Trials Network (PTN) – Pharmacometrics Core (NICHD)
• UCSD HIV Neurobehavioral Research Center (HNRC – S Letendre, R
Ellis)
• CFAR – TB genotype-phenotype PK/PD simulations (T Rodwell)
• Auranofin Phase I – PK / Safety (S Reed)
• SSPPS-Pfizer Clinical Pharmacology-Oncology Fellowship Training
Center Research in Pediatric and
Developmental Pharmacology (NICHD U54)
UC San Diego - E Capparelli / V Nizet
Projects
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Other Centers
Colistimethate Dose
• National Children’s Hospital: J
Optimization in Infants and
van den Anker / E Hoffman
Children – J Bradley / J Le
• Duchene’s Dystrophy –
Drug-Drug Interactions between
Antisense therapy
Pharmaceutical and
• New York U (Downstate): J
Endogenous Antibiotics –
Aranda
G Sakoulas
Developmental Aspects of
• Retinopathy of prematurity –
Aminopenicillin Clearance –
Caffeine / NSAIDS /. VEG
S Nigam
inhibitors
Pilots –
• Indiana: D Flockhart / Jamie
Cathelicidin
Renbarger
Ampicillin
• Emphasis: Oncology – VCR
Renal Development
neurotoxicity, biomarkers
Furosemide
Core Expertise –
IMPAACT Pediatric
Pharmacology Laboratory
Overview
• NIH supported Peds Pcgy Lab
since 1992
• Other IMPAACT Pcgy Labs –
UAB, Colorado, Cape Town
• PPL Investigators
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E Capparelli – PI
B. Best – Pcgst
S Rossi – Lab Manager
R Espina – Lab Tech
N Ilog – Lab Tech
• HIV Treatment Committee
• Lab / CPQA Committees
UCSD Lab Focus Areas
• PK/PD of ARVs in pregnancy
• P316, P353, P358, P1039, P1026s,
P1077, P1081
• PK/PD of ARV in infancy
• P239, P331, DACS096, DACS606,
DACS609, DACS610, P1030, P1070
(EFV), P1106 (preemies), P1111 (RPV),
P1112 (VCR01), P1115 (LPV/NVP)
• PK/PD Modeling and Simulation for
Pediatric Dosing Guidelines (WHO,
DNDi)
• 3TC , ABC, LPV, NVP, ZDV, EFV
• CNS Complications
• P1080 (B Best Chair)
Pediatric Trials Network (PTN)
Projects
Organizational Structure
• Supported by NICHD under BPCA
 Leadership Committee – Multi
Center
• Key Investigators / Cores
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• POPS (A Tremoulet / J Le)
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PI: Danny Benjamin PI (Duke)
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Safety and Ethics: R McKinney / K
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Wade (CHOP)
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Pharmacometrics: (PK/PD/DZ) – E
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Capparelli (UCSD)
Clinical Pharmacology: G Kearns •
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(KC Mercy)
Devices: A Muelenaer / M O’Shea •
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Mentorship: J Van Den Anker (DC
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Nat Childrens’)
• Ampicillin
• Methadone
Metronidazole
Fluconazole PPX in infants
Acyclovir (I and II)
Anti-staph trio
Clindamycin
Antibiotic safety (SCAMP)
Midazolam for SE
Lorazepam for SE
TAPE
Lisinopril PK
Drugs in Obesity
UCSD Pediatric Pharmacology Lab –
Miscellaneous Collaborative Activities
• Praziquantel for Schistosomiasis During Pregnancy (PI J
Freidman - Brown University / Tacloban Philippines)
• Congenital Transmission of T Cruzi - NFX and BZ in
Newborn Infants (P Buekens – Tulane Univ)
• Levetiracetam in Cerebral Malaria (G. Birbeck - U Rochester /
Blantyre Malawi)
• Option B+ for Prevention of Mother to Child HIV
Transmission (MG Fowler & P Musoke – J Hopkins U / Kampala
Uganda)
• IL-6 Blockade in Treated HIV Infection (AIDS 347) (B
Rodriguez - Case Western Reserve U)
• Early Treatment of HIV in Infants (R. Shapiro - Harvard /
Botswana)
• VCR01 anti-HIV monoclonal antibodies VRC601,
VRC602 (B Graham –VRC/NIAID)
Edmund Capparelli –
Proposed Collaborations with SSPPS Faculty
• Current SSPPS Collaborators
• V Nizet, B Best, J Le, J Momper
• Areas for New SSPPS Collaborators
• PK/PD Modeling – Pediatric Drug Development
• Oncology (I Saunders, J Ma)
• Training SSPPS-Pfizer fellows
• PREDICT Study (R Kuzrock)
• Phase I Clinic
• Development of quantitative assays
• Peds Oncology –
• dual PI-3K /BET bromodomain inhibitor
• Pediatric PI-3K (SF-1126) neuroblastoma study
• Seizures associated with neurotoxins – NICHD – pediatricbioterrorism initiatives, P Taylor, J Momper
• Renal Development – Nephrotoxicity (L Awdishu)
Brookie Best - Research Interests
• Primary interest is pharmacokinetic (PK) and dosing studies in
pregnant and breastfeeding women
• HIV experience, starting in TB, postpartum contraceptives, Breast
Milk Biorepository
• Others:
• pediatric PK (Kawasaki disease, GI, psych meds, etc.), any HIV
PK, HIV CNS PK, pharmacy education, training grants
Brookie Best – Proposed Collaborations
• Current/Past SSPPS Collaborators
• Capparelli, Atayee, Ma, Morello, Singh, Hirsch, Taylor, Adler,
Daniels, Brandl (new), Awdishu, Anderson
• New Areas:
• Breast Milk Biorepository, Short-term Training Grants, PK of
various drugs in pregnant women or in children
Jennifer Le - Research Interests
Primary interest in pediatric infectious diseases
• Pharmacokinetic/pharmacodynamic (PK-PD) studies
• Antibacterial agents
• Antifungal agents
• Antimicrobial resistance studies
• Methicillin-resistant S. aureus
• Extended-spectrum beta-lactamase
• Patient outcome studies
• Safety and effectiveness of antimicrobial agents
Other interests
• Patient outcome studies in adults
• Community-based medical center partnerships
• 5 hospitals and many outpatient entities
Research Sites
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MemorialCare Health System
• Nonprofit integrated delivery system that includes six top hospitals
• Long Beach Memorial, Miller Children's & Women's Hospital Long
Beach, Community Hospital Long Beach, Orange Coast Memorial,
Saddleback Memorial Laguna Hills and San Clemente
• Medical groups – MemorialCare Medical & Greater Newport Physicians
• Seaside Health Plan
• Numerous outpatient health centers, imaging and surgery centers in
through Los Angeles and Orange County
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Miller Children’s and Women’s Hospital of Long Beach
• 383 pediatric beds and 94 women’s beds
Long Beach Memorial
• 462 beds, level 2 trauma center
Rady Children’s Hospital – J Bradley
• 449 pediatric beds
Children’s Hospital of Orange County – M Jahng and F Adler-Shohet
• 279 pediatric beds
Proposed Collaborations with SSPPS Faculty
Current
• PK-PD modeling studies, especially in pediatrics (E Capparelli, J
Bradley, A Tremoulet) – funded by NIAID, NICHD, Foundations
• Antimicrobial resistance study (V Nizet, G Sakoulas) – funded by
NIAID
• Antimicrobial resistance surveillance (national and international
SENTRY) – funded by JMI Laboratories
Areas for New SSPPS Collaborations
• Antimicrobial resistance studies, including collection of clinical
isolates
• Patient outcome studies for pediatric and adult infections
• Physiologic-based modeling for pneumonia (J Bradley, D Gonzales)
• Bridge for studies conducted at community-based medical centers
Jeremiah Momper: Research Interests
• Pediatric Clinical Pharmacology and Drug Development
• Exposure-response relationships in adults and pediatric patients
with CINV and PONV (funded by FDA)
• Kidney Disease and Transplantation
• Hormonal regulation of drug metabolizing enzymes (D McKay, R
Tukey, S Chen)
• Pharmacodynamics of statins in transplant patients with
cyclosporine-mediated OATP1B1 inhibition
• Biodefense Research
• Preclinical pharmacokinetics of novel reactivators of
organphosphate Inhibited cholinesterases (P Taylor, Z Radic)
Proposed Collaborations
• Analytical support (LC-MS/MS) for faculty interested in pre-clinical
and clinical PK/PD studies in various therapeutic areas
• Pediatric drug safety
• Pediatric oncology