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Hepatic drug clearance in patients with mild cystic fibrosis
Author(s) -
Kearns Gregory L.,
Crom William R.,
Karlson Karl H.,
Mallory George B.,
Evans William E.
Publication year - 1996
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/s0009-9236(96)90181-2
Subject(s) - cystic fibrosis , medicine , drug , metabolic clearance rate , pharmacology , gastroenterology , pharmacokinetics
The plasma disposition of three model substrates (lorazepam, indocyanine green, and antipyrine) and the formation clearance of antipyrine metabolites (3‐hydroxymethylantipyrine, norantipyrine, and 4‐hydroxyantipyrine) were evaluated in 15 subjects with mild cystic fibrosis and in 15 healthy control subjects. Plasma clearance was significantly greater in patients with cystic fibrosis for both lorazepam (1.7 ± 0.4 versus 1.2 ± 0.5 ml/min/kg) and indocyanine green (14.2 ± 6.1 versus 9.1 ± 3.0 ml/min/kg). In contrast, the clearance of antipyrine was not significantly different (1.0 ± 0.7 versus 0.8 ± 0.3 ml/min/kg), but the formation clearance for 3‐hydroxymethylantipyrine was significantly greater in patients with cystic fibrosis. Lorazepam and antipyrine apparent steady‐state volume of distribution were not different between groups. These results suggest that clearance of drugs that undergo conjugation (e.g., lorazepam) or biliary excretion (e.g., indocyanine green) is increased in patients with mild cystic fibrosis. In contrast, the increased formation clearance of only one antipyrine metabolite suggests that alterations in clearance of drugs metabolized by cytochrome P450 enzymes are substrate specific and isoform specific in patients with cystic fibrosis. Clinical Pharmacology & Therapeutics (1996) 59 , 529–540; doi: