scholarly journals Cytochrome P450-Based Drug-Drug Interactions of Vonoprazan In Vitro and In Vivo

2020 ◽  
Vol 11 ◽  
Author(s):  
Yiran Wang ◽  
Changxiong Wang ◽  
Shuanghu Wang ◽  
Quan Zhou ◽  
Dapeng Dai ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Drug Interactions

Inhibition of Desipramine Hydroxylation (Cytochrome P450-2D6) in Vitro by Quinidine and by Viral Protease Inhibitors: Relation to Drug Interactions in Vivo

1998 ◽  
Vol 87 (10) ◽  
pp. 1184-1189 ◽  
Author(s):  
Lisa L. von Moltke ◽  
David J. Greenblatt ◽  
Su Xiang Duan ◽  
Johanna P. Daily ◽  
Jerold S. Harmatz ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Drug Interactions ◽  
Protease Inhibitors ◽  
Cytochrome P450 2D6 ◽  
Viral Protease ◽  
P450 2D6

scholarly journals Metabolic Drug-Drug Interaction Potential of Macrolactin A and 7-O-Succinyl Macrolactin A Assessed by Evaluating Cytochrome P450 Inhibition and Induction and UDP-Glucuronosyltransferase InhibitionIn Vitro

2014 ◽  
Vol 58 (9) ◽  
pp. 5036-5046 ◽  
Author(s):  
Soo Hyeon Bae ◽  
Min Jo Kwon ◽  
Jung Bae Park ◽  
Doyun Kim ◽  
Dong-Hee Kim ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Drug Interactions ◽  
Antitumor Agents ◽  
Content Type ◽  
Dependent Inactivation ◽  
Competitive Inhibitors ◽  
Macrolactin A ◽  
Clinically Significant

ABSTRACTMacrolactin A (MA) and 7-O-succinyl macrolactin A (SMA), polyene macrolides containing a 24-membered lactone ring, show antibiotic effects superior to those of teicoplanin against vancomycin-resistant enterococci and methicillin-resistantStaphylococcus aureus. MA and SMA are currently being evaluated as antitumor agents in preclinical studies in Korea. We evaluated the potential of MA and SMA for the inhibition or induction of human liver cytochrome P450 (CYP) enzymes and UDP-glucuronosyltransferases (UGTs)in vitroto assess their safety as new molecular entities. We demonstrated that MA and SMA are potent competitive inhibitors of CYP2C9, withKivalues of 4.06 μM and 10.6 μM, respectively. MA and SMA also weakly inhibited UGT1A1 activity, withKivalues of 40.1 μM and 65.3 μM, respectively. However, these macrolactins showed no time-dependent inactivation of the nine CYPs studied. In addition, MA and SMA did not induce CYP1A2, CYP2B6, or CYP3A4/5. On the basis of anin vitro-in vivoextrapolation, our data strongly suggested that MA and SMA are unlikely to cause clinically significant drug-drug interactions mediated via inhibition or induction of most of the CYPs involved in drug metabolismin vivo, except for the inhibition of CYP2C9 by MA. Similarly, MA and SMA are unlikely to inhibit the activity of UGT1A1, UGT1A4, UGT1A6, UGT1A9, and UGT2B7 enzymesin vivo. Although further investigations will be required to clarify thein vivointeractions of MA with CYP2C9-targeted drugs, our findings offer a clearer understanding and prediction of drug-drug interactions for the safe use of MA and SMA in clinical practice.

Integrated in Vitro Analysis for the in Vivo Prediction of Cytochrome P450-Mediated Drug-Drug Interactions

2008 ◽  
Vol 36 (6) ◽  
pp. 1126-1134 ◽  
Author(s):  
Dermot F. McGinnity ◽  
Nigel J. Waters ◽  
James Tucker ◽  
Robert J. Riley
Keyword(s):  
Cytochrome P450 ◽  
Drug Interactions ◽  
Vitro Analysis ◽  
In Vitro Analysis
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