Altered prednisolone pharmacokinetics in patients with cystic fibrosis. 
Prednisolone pharmacokinetics were evaluated in eight patients with cystic fibrosis (CF) (aged 1.8 to 20 years) by assessing absorption of orally administered prednisone (in its active form, prednisolone) and elimination of prednisolone after intravenous administration.  After an overnight fast, subjects received intravenously administered doses of prednisolone or orally administered doses of prednisone, 40 mg/1.73 m2 body surface area, before a standardized breakfast.  Serial blood samples were collected for 12 hours and analyzed for prednisolone concentration.  Prednisolone pharmacokinetics were compared in eight age-matched patients with asthma who required steroids after intravenous administration of prednisolone.  The prednisolone pharmacokinetic parameters derived demonstrated an increased total clearance (by 60%), an increased volume of distribution (by 46%), a lower peak concentration (by 35%), and no difference in elimination half-life in patients with CF compared with those with asthma.  Bioavailability averaged 88.4% +/- 20.1% of the administered dose.  Prednisolone clearance was markedly increased in those with CF.  There was a proportional increase in nonrenal clearance, with no difference in renal clearance in those with asthma or CF.  The plasma protein binding of prednisolone was only slightly decreased in patients with CF and did not account for the observed pharmacokinetic alteration.  The marked increase in prednisolone clearance may necessitate the use of more frequent or higher doses of this steroid in the treatment of patients with CF, leading to a potentially less favorable benefit/risk ratio.