Malabsorption blood test: Assessing fat absorption in patients with cystic fibrosis and pancreatic insufficiency

Abstract

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.

Keywords: cystic fibrosis; fat malabsorption; pancreatic enzyme replacement therapy; pancreatic function test.

Conflict of interest statement

Disclosures: VAS is the inventor of the MBT. All other authors have no financial conflicts to disclose.

© 2015, The American College of Clinical Pharmacology.

Figures

Figure 1

a–d. Diagnostic plots from the final population pharmacokinetics model. a) PA observed vs. population predicted. b) PA observed vs. individual predicted. c)HA observed vs. population predicted and d)HA observed vs. individual predicted.

Figure 2

Visual predictive check for healthy subjects. Open circles are observed concentrations, solid line is the median from 500 simulated trials, dashed lines are the simulated 5th and 95th percentiles.

Figure 3

Visual predictive check for subjects with CF administered pancreatic enzymes with the MBT. Open circles are observed concentrations, solid line is the median from 500 simulated trials, dashed lines are the simulated 5th and 95th percentiles.

Figure 4

Visual predictive check for subjects with CF administered pancreatic enzymes at varying times relative to MBT. Open circles are observed concentrations, solid line is the median from 500 simulated trials, dashed lines are the simulated 5th and 95th percentiles.