title: Pharmacokinetic analysis of 14C-ursodiol in newborn infants using accelerator mass spectrometry.
abstract: Pharmacokinetic studies in the neonatal population are often limited by the small volume of blood that can be collected. The high sensitivity of (14) C-accelerator mass spectrometry (AMS) enables pharmacokinetic studies to be conducted with greatly reduced sample volumes. We demonstrated the utility of AMS in infants by studying the plasma pharmacokinetic behavior of nanogram doses of (14) C-ursodiol administered as a non-perturbing microdose or as a microtracer with therapeutic doses of non-labeled ursodiol in infants. Five non-cholestatic infants were administered 3 consecutive oral microdoses of (14) C-ursodiol: 8 ng (1.0 nCi), 26 ng (3.3 nCi), and 80 ng (10 nCi) 48 hours apart. Three additional infants with cholestasis were administered a single 80 ng (10.0 nCi) oral dose of (14) C-ursodiol together with a therapeutic dose of 40 mg/kg of non-labeled ursodiol. A pharmacokinetic model describing ursodiol concentrations was developed using nonlinear mixed-effects modeling. The pharmacokinetics of ursodiol in this pilot study were best described by a two-compartment model with first-order elimination. This study demonstrates the feasibility and utility of microdose and microtrace methodology in pediatric research.
authors.affiliation: Rosa & Co LLC, San Carlos, CA, USA.
authors.forename: Toufigh
authors.initials: T
authors.lastname: Gordi
authors.forename: Rebecca
authors.initials: R
authors.lastname: Baillie
authors.forename: Le T
authors.initials: le T
authors.lastname: Vuong
authors.forename: Saira
authors.initials: S
authors.lastname: Abidi
authors.forename: Stephen
authors.initials: S
authors.lastname: Dueker
authors.forename: Herbert
authors.initials: H
authors.lastname: Vasquez
authors.forename: Priscilla
authors.initials: P
authors.lastname: Pegis
authors.forename: Andrew O
authors.initials: AO
authors.lastname: Hopper
authors.forename: Gordon G
authors.initials: GG
authors.lastname: Power
authors.forename: Arlin B
authors.initials: AB
authors.lastname: Blood
mesh_terms: D002250:Carbon Radioisotopes; D002779:Cholestasis / Q000097:blood / Q000378:metabolism; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D013058:Mass Spectrometry / Q000379:methods*; D008954:Models, Biological; D011849:Radioactive Tracers; D014580:Ursodeoxycholic Acid / Q000008:administration & dosage* / Q000493:pharmacokinetics*
chemical_list: D002250:Carbon Radioisotopes; D011849:Radioactive Tracers; D014580:Ursodeoxycholic Acid
keywords: accelerator mass spectrometry; bile acid; infants; microdosing; pediatrics; pharmacokinetics; ursodiol