Premium
A population pharmacokinetic model for pentadecanoic acid (PA) and triheptadecanoic acid (THA) exposure following administration of a malabsorption blood test (MBT) to quantify steatorrhea
Author(s) -
Mondick J.,
Barrett J.,
Schall J.,
Mascarenhas M.,
Stallings V.
Publication year - 2005
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/j.clpt.2004.12.082
Subject(s) - pharmacokinetics , bioavailability , nonmem , medicine , population , pharmacology , oral administration , gastroenterology , environmental health
Background Metabolism of THA to heptadecanoic acid (HA) requires pancreatic lipase, which is known to be deficient in cystic fibrosis (CF) patients. We developed a preliminary pharmacokinetic model to explore the PA and HA time course following administration of the MBT. We will use this model to develop guidance on MBT administration and optimal sampling for discerning the degree of fat malabsorption. Methods A retrospective analysis was performed using plasma concentrations from 31 healthy and 11 CF subjects. Data were analyzed via nonlinear mixed effect modeling using NONMEM. Results The structural pharmacokinetic model was based on 2 compartments with first order elimination, Weibull absorption kinetics, and a term for endogenous PA and HA levels. The HA bioavailability in CF patients relative to healthy subjects was 42.4%. Mean (CV%) HA population estimates for V c , k e , k 12 , k 21 , and k a were 17.2 (50.8) L, 0.596 (85.8) hr −1 , 0.439 hr −1 , 0.0330 hr −1 , and 0.336 (37.7) hr −1 . Fasting, enzyme administration and the presence of CF significantly affected the HA absorption rate. Conclusions This preliminary model provides good prediction for systemic PA and HA exposure following administration of the MBT to healthy subjects and CF patients. We are conducting additional studies to further improve the model to predict exposure in pediatric populations and refine the influence of gastric emptying on the absorption process. Clinical Pharmacology & Therapeutics (2005) 77 , P50–P50; doi: 10.1016/j.clpt.2004.12.082