Inhibition of human cytochromes P450 in vitro by ritonavir and cobicistat
Objectives: Ritonavir and cobicistat are strong inhibitors of human cytochrome P450-3A (CYP3A) isoforms, and are used clinically as pharmacokinetic boosting agents for other antiretroviral drugs. Data reported by the manufacturer suggest that cobicistat is a more selective inhibitor of CYP3A than ri...
Gespeichert in:
| Hauptverfasser: | , |
|---|---|
| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
29 September 2017
|
| In: |
Journal of pharmacy and pharmacology
Year: 2017, Jahrgang: 69, Heft: 12, Pages: 1786-1793 |
| ISSN: | 2042-7158 |
| DOI: | 10.1111/jphp.12820 |
| Online-Zugang: | Verlag, Volltext: http://dx.doi.org/10.1111/jphp.12820 Verlag, Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1111/jphp.12820 
|
| Verfasserangaben: | Md Amin Hossain, Timothy Tran, Tianmeng Chen, Gerd Mikus and David J. Greenblatt |
MARC
| LEADER | 00000caa a2200000 c 4500 | ||
|---|---|---|---|
| 001 | 1580848478 | ||
| 003 | DE-627 | ||
| 005 | 20220815004700.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 180911s2017 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1111/jphp.12820 |2 doi | |
| 035 | |a (DE-627)1580848478 | ||
| 035 | |a (DE-576)510848478 | ||
| 035 | |a (DE-599)BSZ510848478 | ||
| 035 | |a (OCoLC)1341018303 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rda | ||
| 041 | |a eng | ||
| 084 | |a 33 |2 sdnb | ||
| 100 | 1 | |a Hossain, Md. Amin |e VerfasserIn |0 (DE-588)1166686051 |0 (DE-627)1030551081 |0 (DE-576)510848591 |4 aut | |
| 245 | 1 | 0 | |a Inhibition of human cytochromes P450 in vitro by ritonavir and cobicistat |c Md Amin Hossain, Timothy Tran, Tianmeng Chen, Gerd Mikus and David J. Greenblatt |
| 264 | 1 | |c 29 September 2017 | |
| 300 | |a 8 | ||
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Gesehen am 11.09.2018 | ||
| 520 | |a Objectives: Ritonavir and cobicistat are strong inhibitors of human cytochrome P450-3A (CYP3A) isoforms, and are used clinically as pharmacokinetic boosting agents for other antiretroviral drugs. Data reported by the manufacturer suggest that cobicistat is a more selective inhibitor of CYP3A than ritonavir. However, this claim has not been validated in clinical studies. This study evaluated the in-vitro inhibitory potency of ritonavir and cobicistat vs a series of human CYP isoforms. Method: The model system utilized human liver microsomes and isoform-selective index substrates. Key findings: Ritonavir and cobicistat both were strong inhibitors of CYP3A4, with IC50 values of 0.014 and 0.032 μm, respectively. A component of inhibition was time-dependent (mechanism-based). Neither drug meaningfully inhibited CYP1A2 (IC50 > 150 μm). CYP2B6, CYP2C9, CYP2C19 and CYP2D6 were inhibited by both drugs, but with IC50 values exceeding 6 μm. Conclusions: Consistent with previous reports, both ritonavir and cobicistat were highly potent inhibitors of CYP3A. Both drugs were weaker inhibitors of other human CYPs, with IC50 values at least two orders of magnitude higher. There was no evidence of a meaningful difference in selectivity between the two drugs. | ||
| 650 | 4 | |a cobicistat | |
| 650 | 4 | |a cytochromes P450 | |
| 650 | 4 | |a in-vitro metabolism | |
| 650 | 4 | |a metabolic inhibition | |
| 650 | 4 | |a ritonavir | |
| 700 | 1 | |a Mikus, Gerd |e VerfasserIn |0 (DE-588)110903137 |0 (DE-627)691097941 |0 (DE-576)336988710 |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Journal of pharmacy and pharmacology |d Oxford : Oxford University Press, 1949 |g 69(2017), 12, Seite 1786-1793 |h Online-Ressource |w (DE-627)326977740 |w (DE-600)2041988-0 |w (DE-576)094504156 |x 2042-7158 |7 nnas |a Inhibition of human cytochromes P450 in vitro by ritonavir and cobicistat |
| 773 | 1 | 8 | |g volume:69 |g year:2017 |g number:12 |g pages:1786-1793 |g extent:8 |a Inhibition of human cytochromes P450 in vitro by ritonavir and cobicistat |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1111/jphp.12820 |x Verlag |x Resolving-System |3 Volltext |
| 856 | 4 | 0 | |u https://onlinelibrary.wiley.com/doi/abs/10.1111/jphp.12820 |x Verlag |3 Volltext |
| 951 | |a AR | ||
| 992 | |a 20180911 | ||
| 993 | |a Article | ||
| 994 | |a 2017 | ||
| 998 | |g 110903137 |a Mikus, Gerd |m 110903137:Mikus, Gerd |d 910000 |d 910100 |e 910000PM110903137 |e 910100PM110903137 |k 0/910000/ |k 1/910000/910100/ |p 4 | ||
| 999 | |a KXP-PPN1580848478 |e 3025250798 | ||
| BIB | |a Y | ||
| SER | |a journal | ||
| JSO | |a {"title":[{"title":"Inhibition of human cytochromes P450 in vitro by ritonavir and cobicistat","title_sort":"Inhibition of human cytochromes P450 in vitro by ritonavir and cobicistat"}],"person":[{"family":"Hossain","given":"Md. Amin","display":"Hossain, Md. Amin","roleDisplay":"VerfasserIn","role":"aut"},{"display":"Mikus, Gerd","roleDisplay":"VerfasserIn","role":"aut","family":"Mikus","given":"Gerd"}],"recId":"1580848478","language":["eng"],"note":["Gesehen am 11.09.2018"],"type":{"media":"Online-Ressource","bibl":"article-journal"},"id":{"doi":["10.1111/jphp.12820"],"eki":["1580848478"]},"origin":[{"dateIssuedDisp":"29 September 2017","dateIssuedKey":"2017"}],"name":{"displayForm":["Md Amin Hossain, Timothy Tran, Tianmeng Chen, Gerd Mikus and David J. Greenblatt"]},"relHost":[{"physDesc":[{"extent":"Online-Ressource"}],"id":{"issn":["2042-7158"],"doi":["10.1111/(ISSN)2042-7158"],"eki":["326977740"],"zdb":["2041988-0"]},"origin":[{"publisherPlace":"Oxford ; London ; Oxford [u.a.]","publisher":"Oxford University Press ; Pharmaceutical Press ; Wiley-Blackwell","dateIssuedKey":"1949","dateIssuedDisp":"1949-"}],"language":["eng"],"recId":"326977740","type":{"bibl":"periodical","media":"Online-Ressource"},"disp":"Inhibition of human cytochromes P450 in vitro by ritonavir and cobicistatJournal of pharmacy and pharmacology","note":["Gesehen am 09.07.24"],"titleAlt":[{"title":"JPP"}],"part":{"issue":"12","pages":"1786-1793","year":"2017","extent":"8","text":"69(2017), 12, Seite 1786-1793","volume":"69"},"pubHistory":["1.1949 -"],"title":[{"title_sort":"Journal of pharmacy and pharmacology","subtitle":"JPP ; an international journal of pharmaceutical science","title":"Journal of pharmacy and pharmacology"}]}],"physDesc":[{"extent":"8 S."}]} | ||
| SRT | |a HOSSAINMDAINHIBITION2920 | ||