Clinically significant CYP2C inhibition by noscapine but not by glucosamine.
Noscapine and glucosamine reportedly interact with warfarin. We investigated the effects of these drugs on various cytochrome P450 (CYP) activity markers. Twelve healthy subjects were phenotyped at baseline and during separate treatments with noscapine and glucosamine. Whereas glucosamine had no significant effect on CYP activity, noscapine caused marked inhibition of CYP2C9 (4.9-fold increase in urinary losartan/E3174 ratio) and CYP2C19 (3.6-fold increase in the plasma omeprazole/5-hydroxyomeprazole ratio). Noscapine-dependent inhibition of CYP2C9 may explain the interaction with warfarin.
Rosenborg
S
S
Karolinska Institutet, Department of Laboratory Medicine, Division of Clinical Pharmacology, Karolinska University Hospital Huddinge, Stockholm, Sweden. staffan.rosenborg@ki.se
Stenberg
M
M
Otto
S
S
Ostervall
J
J
Masquelier
M
M
Yue
Q-Y
QY
Bertilsson
L
L
Eliasson
E
E
D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000493:pharmacokinetics; D000328:Adult; D000925:Anticoagulants / Q000493:pharmacokinetics; D000996:Antitussive Agents / Q000494:pharmacology; D001189:Aryl Hydrocarbon Hydroxylases / Q000037:antagonists & inhibitors*; D065731:Cytochrome P-450 CYP2C19; D065729:Cytochrome P-450 CYP2C9; D004347:Drug Interactions; D005260:Female; D005944:Glucosamine / Q000494:pharmacology*; D006801:Humans; D019808:Losartan / Q000493:pharmacokinetics; D008297:Male; D008875:Middle Aged; D009665:Noscapine / Q000494:pharmacology*; D009853:Omeprazole / Q000493:pharmacokinetics; D010641:Phenotype; D014859:Warfarin / Q000493:pharmacokinetics; D055815:Young Adult
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000925:Anticoagulants; D000996:Antitussive Agents; D014859:Warfarin; D009665:Noscapine; C049963:5-hydroxymethylomeprazole; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D019808:Losartan; D009853:Omeprazole; D005944:Glucosamine