Altered PABA pharmacokinetics in cystic fibrosis. Implications for bentiromide test.
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 of T1/2 of PABA was significantly shorter in CF patients (58 +/- 21 min) compared to controls (93.5 +/- 28) (P less than 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 and T1/2 (r = 0.51 P less than 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.(ABSTRACT TRUNCATED AT 250 WORDS)
D010129:4-Aminobenzoic Acid / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*; D000042:Absorption; D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D062365:Aminobenzoates / Q000378:metabolism*; D003550:Cystic Fibrosis / Q000378:metabolism* / Q000503:physiopathology; D006801:Humans; D007700:Kinetics; D010179:Pancreas / Q000503:physiopathology; D062366:para-Aminobenzoates
D062365:Aminobenzoates; D062366:para-Aminobenzoates; C006717:bentiromide; D010129:4-Aminobenzoic Acid