In vitro study of the inhibition and induction of human cytochromes P450 by crystalline glucosamine sulfate.
The induction and inhibition of human hepatic cytochrome P450 (CYP) isoforms by crystalline glucosamine sulfate (CGS) was investigated in vitro. Inhibition of CYP1A2, CYP2E1, CYP2C19, CYP2C9, CYP2D6, and CYP3A4 by CGS was assessed using recombinant human enzymes incubated with CGS (up to 3 mM expressed as free base). Induction of CYP1A2, CYP2B6, CYP2C9, CYP2C19 and CYP3A4 by CGS (0.01, 0.3 and 3 mM) was evaluated in cryopreserved human hepatocytes, by determining CYP mRNA expression using quantitative RT-PCR. CGS produced no inhibition or induction of any the CYP enzymes tested at concentrations hundred folds higher than the steady state peak plasma concentrations (approximately 10 microM) observed in man after therapeutic doses of CGS of 1500 mg once a day. Therefore, no clinically relevant metabolic interactions are expected between CGS and co-administered drugs that are substrates of the CYP enzymes investigated.
Persiani
Stefano
S
Rottapharm SpA, Monza, Italy. stefano.persiani@rottapharm.com
Canciani
Luca
L
Larger
Patrice
P
Rotini
Roberto
R
Trisolino
Giovanni
G
Antonioli
Diego
D
Rovati
Lucio C
LC
D002478:Cells, Cultured; D003460:Crystallization; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D005944:Glucosamine / Q000494:pharmacology*; D022781:Hepatocytes / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D008297:Male; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods
D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors; D012333:RNA, Messenger; D003577:Cytochrome P-450 Enzyme System; D005944:Glucosamine