1 / 10

Mario Sampson, PharmD Duke Clinical Research Institute

Pharmacokinetics and Safety of Metronidazole in Preterm Infants: Validation of Dried Blood Spot Sampling. Mario Sampson, PharmD Duke Clinical Research Institute University of North Carolina Eshelman School of Pharmacy. Background. In preterm infants, intra-abdominal infections are deadly

barton
Download Presentation

Mario Sampson, PharmD Duke Clinical Research Institute

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript


  1. Pharmacokinetics and Safety of Metronidazole in Preterm Infants: Validation of Dried Blood Spot Sampling Mario Sampson, PharmD Duke Clinical Research Institute University of North Carolina Eshelman School of Pharmacy

  2. Background • In preterm infants, intra-abdominal infections are deadly • These infections are polymicrobial, including anaerobes • Metronidazole has excellent anti-anaerobic activity • Pharmacokinetic data of metronidazole in preterm infants are limited • Blood volume is a limiting factor for studies in neonates • Dried blood spots require 10 times less blood per sample vs. plasma

  3. Methods • Multicenter (N=3), open-label, PK study • N=24 • Population • Gestational age at birth <32 weeks • Postnatal age (PNA) <91 days • Suspected serious infection • Dosing (intravenous) • Loading dose 15 mg/kg • Maintenance dose 7.5 mg/kg every 12-24 hours for 5 days

  4. Methods • Sampling • Paired plasma and dried blood spots collected if possible Last dose, PNA < 14 days 24-25 48-49 72-73 hours Dose 1, & 3-5 12-13 24-25 36-37 hours Last dose, PNA ≥ 14 days -0.5 0.2 3-4 4-6 hours • Population PK • Nonlinear mixed effects modeling using NONMEM software and bootstrapping to evaluate precision of parameters • Plasma and dried blood spot samples analyzed separately • Plasma and dried blood spot paired concentrations analyzed by linear regression

  5. Subject Demographics

  6. Population Pharmacokinetics • Final model: Clearance (L/h) = 0.0421 * Weight * (Postnatal Age/27)0.451 and Volume (L) = 0.948 * Weight

  7. Population Pharmacokinetic Parameters

  8. Dried Blood Spots r2=0.95, slope=0.80 [95% CI, 0.74, 0.85], p<0.001 r2=0.85, p<0.001 N=46 paired samples

  9. Adverse Events

  10. Conclusions • Metronidazole clearance increased with postnatal age • Clearance finding expected with development • The bias in population clearance and volume parameter estimates was <10% using dried blood spots • DBS sampling can be used to evaluate metronidazole pharmacokinetics Acknowledgments • Pediatric Trials Network • Daniel Benjamin Jr. • Edmund Capparelli • Gregory Kearns • Philip Brian Smith • Michael Cohen-Wolkowiez • Katherine Berezny • Barrie Harper • Enrolling Sites • Children’s Hospital of Orange County - Antonio Arrieta • Duke University Medical Center - James Wynn • Wesley Medical Center - Barry Bloom - Paula Delmore • Data Coordinating Center • EMMES Corporation • NIGMS/NICHD UNC-Duke Collaborative T32 Clinical Pharmacology Postdoctoral Training Grant, National Institutes of Health (1 T32 GM 86330) • Kim Brouwer • Daniel Benjamin Jr. • Paul Watkins • Eunice Kennedy Shriver National Institute of Child Health and Human Development (NIH) • Contract #: HHSN2752010000031 and HHSN201000003I • Task Order #: HHSN27500003 • Best Pharmaceuticals for Children Act • University of North Carolina Eshelman School of Pharmacy

More Related