Altered PABA pharmacokinetics in cystic fibrosis

Abstract

The bentiromide test has been proposed as a useful noninvasive method for assessing exocrine pancreatic function in cystic fibrosis (CF) patients. Following oral administration, this peptide is selectively cleaved by pancreatic chymotrypsin liberating PABA which is passively absorbed. Recent studies have suggested that PABA measured in plasma is superior to the more established method of estimating urinary recovery of this marker. However, in using the plasma test in CF patients, one makes the assumption that the PABA marker has similar distribution and elimination patterns in normal and CF subjects. Since many drugs display altered pharmacokinetics in CF patients, we studied the disposition of PABA following ingestion of free PABA in six controls (age 19–28 years) and 18 CF patients (13–18 years; seven steatorrheic and 11 nonsteatorrheic). Elimination ofT1/2 of PABA was significantly shorter in CF patients (58±21 min) compared to controls (93.5±28) (P<0.005). PABA clearance was similar in the control and CF patients (2.99±1.21 and 3.27±1.02 ml/min/kg, respectively). PABA distribution volume was smaller, although not significantly so, than in the controls (268±107 vs 376±140 ml/kg). Good correlation was found between PABA distribution volume andT1/2 (r=0.51P<0.02). Our simulation data suggest that altered pharmacokinetics of PABA in CF patients would cause their PABA levels to be 7% lower than controls at 90 min, 18% at 120 min, 29% at 150 min, and 38% at 180 min. In an extreme CF case with a shortT1/2 and small distribution volume, PABA levels at 90 min would be 31% lower than that of control. At 180 min, concentrations would be lower by 72%. Our data suggest that a CF patient may have lower levels of PABA than control even in the presence of appropriate pancreatic enzyme activity. These studies indicate that early measurement of plasma PABA (90 min) would minimize this potential error.