J Clin Pharmacol 2015 Aug 23;55(8):854-65. Epub 2015 Mar 23.
Division of Gastroenterology, Hepatology and Nutrition, The Children's Hospital of Philadelphia and University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
The malabsorption blood test (MBT), consisting of pentadecanoic acid (PA), a free fatty acid, and triheptadecanoic acid (THA), a triglyceride that requires pancreatic lipase for absorption of the heptadecanoic acid (HA), was developed to assess fat malabsorption in patients with cystic fibrosis (CF) and pancreatic insufficiency (PI). The objective was to construct a population pharmacokinetic (PK) model to describe PA and HA disposition in healthy subjects and CF subjects. A model was simultaneously fit to PA and HA concentrations, consisting of 1-compartment disposition and a transit model to describe absorption. PA bioavailability estimates for CF subjects without pancreatic enzyme administration (1.07 [0.827, 1.42]) and with enzymes (0.88 [0.72, 1.09]) indicated PA absorption comparable to healthy subjects. HA bioavailability in CF without enzyme administration was 0.0292 (0.0192, 0.0459) and with enzymes increased to 0.606 (0.482, 0.823). In CF, compared with taking enzymes with the MBT, HA bioavailability was further decreased by factors of 0.829 (0.664, 0.979) and 0.78 (0.491, 1.13) with enzymes taken 30 and 60 minutes after MBT, respectively. The MBT detected differences in fat absorption in subjects with CF with and without enzyme administration and with changes in enzyme timing. Future studies will address application of the MBT in CF and other malabsorption diagnoses.