scholarly journals CYP3A4 Substrate

2020 ◽  
Author(s):  
Keyword(s):  
Cyp3a4 Substrate

scholarly journals Cardiac Conduction Safety during Coadministration of Artemether-Lumefantrine and Lopinavir/Ritonavir in HIV-Infected Ugandan Adults

2011 ◽  
Vol 2011 ◽  
pp. 1-4 ◽  
Author(s):  
Pauline Byakika-Kibwika ◽  
Mohammed Lamorde ◽  
Peter Lwabi ◽  
Wilson B. Nyakoojo ◽  
Violet Okaba-Kayom ◽  
...  
Keyword(s):  
Single Dose ◽  
Cardiac Conduction ◽  
Hiv Positive ◽  
Cyp3a4 Inhibitor ◽  
Open Label ◽  
Safety Study ◽  
Serious Adverse Events ◽  
Normal Limits ◽  
Hiv Positive Adults ◽  
Cyp3a4 Substrate

Background. We aimed to assess cardiac conduction safety of coadministration of the CYP3A4 inhibitor lopinavir/ritonavir (LPV/r) and the CYP3A4 substrate artemether-lumefantrine (AL) in HIV-positive Ugandans. Methods. Open-label safety study of HIV-positive adults administered single-dose AL (80/400 mg) alone or with LPV/r (400/100 mg). Cardiac function was monitored using continuous electrocardiograph (ECG). Results. Thirty-two patients were enrolled; 16 taking LPV/r -based ART and 16 ART naïve. All took single dose AL. No serious adverse events were observed. ECG parameters in milliseconds remained within normal limits. QTc measurements did not change significantly over 72 hours although were higher in LPV/r arm at 24 (424 versus 406; P=.02) and 72 hours (424 versus 408; P=.004) after AL intake. Conclusion. Coadministration of single dose of AL with LPV/r was safe; however, safety of six-dose AL regimen with LPV/r should be investigated.

scholarly journals Effects of tomato juice on the pharmacokinetics of CYP3A4-substrate drugs

2017 ◽  
Vol 12 (5) ◽  
pp. 464-469 ◽  
Author(s):  
Atsuko Ohkubo ◽  
Tomomi Chida ◽  
Hidetomo Kikuchi ◽  
Tadashi Tsuda ◽  
Katsuyoshi Sunaga
Keyword(s):  
Tomato Juice ◽  
Cyp3a4 Substrate

Neue orale Antikoagulantienaus klinisch pharmakologischer Sicht

2012 ◽  
Vol 69 (11) ◽  
pp. 657-660 ◽  
Author(s):  
Haschke
Keyword(s):  
Vitamin K ◽  
Intrakranielle Blutungen ◽  
Cyp3a4 Substrate ◽  
Faktor Xa

Die neuen oralen Antikoagulantien wie die Faktor Xa-Hemmer Rivaroxaban und Apixaban oder der Thrombin-Hemmer Dabigatran versprechen eine einfachere Handhabung als die altbekannten Vitamin K-Antagonisten. Trotz Wegfallen des Routine-Monitorings ist auch bei den neuen Substanzen aufgrund ihrer pharmakologischen Eigenschaften in bestimmten Situationen mit erheblichen Schwankungen der Exposition zu rechnen. Dabigatran wird überwiegend unverändert renal elimiert, entsprechend muss bei eingeschränkter Nierenfunktion die Dosis reduziert werden. Die Faktor Xa-Hemmer sind CYP3A4-Substrate und dürfen nicht zusammen mit potenten CYP3A4-Hemmern kombiniert werden. Bei Blutungen oder thromboembolischen Ereignissen unter Therapie kann ein gezieltes Monitoring der Wirkstoffkonzentration oder der anti-FXa- bzw. der anti-FIIa-Aktivität bei der Ursachensuche hilfreich sein. Im Gegensatz zu den Vitamin K-Antagonisten oder Heparin stehen für die neuen Antikoagulantien keine Antidote zur Verfügung und das optimale Vorgehen bei lebensbedrohlichen Blutungen ist noch nicht definiert. Für gewisse Indikationen wie die Thromboembolie-Prophylaxe bei akut erkrankten medizinischen Patienten stehen (noch) keine Studiendaten zur Verfügung. Bezüglich Lokalisation der Blutungen verfügen die neuen Substanzen über ein im Vergleich zu Vitamin K-Antagonisten leicht anderes Profil (weniger intrakranielle Blutungen) und die Erfahrungen bei Langzeitanwendung (> 5 Jahre) sind limitiert. Aus diesen Gründen erfordert der Einsatz der neuen Antikoagulantien trotz Wegfallen des Routine-Monitorings eine sorgfältige klinische Überwachung der Patienten unter Berücksichtigung von Co-Medikation und Co-Morbidität um eine sichere Therapie zu gewährleisten.

Phenylalanine and Tryptophan Scanning Mutagenesis of CYP3A4 Substrate Recognition Site Residues and Effect on Substrate Oxidation and Cooperativity†

Biochemistry ◽  
2001 ◽  
Vol 40 (34) ◽  
pp. 10150-10160 ◽  
Author(s):  
Tammy L. Domanski ◽  
You-Ai He ◽  
Kishore K. Khan ◽  
Fabienne Roussel ◽  
Qinmi Wang ◽  
...  
Keyword(s):  
Substrate Recognition ◽  
Substrate Oxidation ◽  
Recognition Site ◽  
Cyp3a4 Substrate

scholarly journals Evaluation of Doravirine Pharmacokinetics When Switching from Efavirenz to Doravirine in Healthy Subjects

2016 ◽  
Vol 61 (2) ◽  
Author(s):  
Ka Lai Yee ◽  
Rosa I. Sanchez ◽  
Patrice Auger ◽  
Rachael Liu ◽  
Li Fan ◽  
...  
Keyword(s):  
Plasma Concentration ◽  
Healthy Subjects ◽  
Geometric Mean ◽  
Transcriptase Inhibitor ◽  
Open Label ◽  
Genetic Barrier ◽  
Fixed Sequence ◽  
Time Curve ◽  
Cyp3a4 Substrate

ABSTRACT Doravirine is a novel, potent nonnucleoside reverse transcriptase inhibitor (NNRTI) for the treatment of patients with human immunodeficiency virus type 1 (HIV-1) infection that demonstrates a high genetic barrier to resistance and that has been well tolerated in studies to date. Doravirine is a candidate for patients switching from less-well-tolerated NNRTIs, such as efavirenz. While doravirine is a cytochrome P450 3A4 (CYP3A4) substrate, efavirenz induces CYP3A4; therefore, the pharmacokinetics of both drugs following a switch from efavirenz to doravirine were assessed. This was a 3-period, fixed-sequence, open-label study. Healthy adults were dosed with doravirine at 100 mg for 5 days once daily (QD) (period 1). Following a 7-day washout, efavirenz was administered at 600 mg QD for 14 days (period 2). Subsequently, doravirine was administered at 100 mg QD for 14 days (period 3). Blood samples were collected for pharmacokinetic analyses. Twenty healthy subjects were enrolled, and 17 completed the study. One day after efavirenz cessation, the doravirine area under the concentration-time curve from predosing to 24 h postdosing (AUC0–24), maximum observed plasma concentration (C max), and observed plasma concentration at 24 h postdosing (C 24) were reduced by 62%, 35%, and 85%, respectively, compared with the values with no efavirenz pretreatment. These decreases recovered to 32%, 14%, and 50% for AUC0–24, C max, and C 24, respectively, by day 14 after efavirenz cessation. The doravirine C 24 reached projected therapeutic trough concentrations, based on in vitro efficacy, on day 2 following efavirenz cessation. Geometric mean efavirenz concentrations were 3,180 ng/ml on day 1 and 95.7 ng/ml on day 15, and efavirenz was present at therapeutic concentrations (>1,000 ng/ml) until day 4. Though doravirine exposure was transiently decreased following efavirenz treatment cessation, dose adjustment may not be necessary to maintain therapeutic concentrations of at least one drug during switching in a virologically suppressed population.

Sign in / Sign up

Export Citation Format

Share Document