Read by QxMD icon Read

rifampicin AND pharmacokinetics

Smriti Srivastava, Devla Bimal, Kapil Bohra, Balram Singh, Prija Ponnan, Ruchi Jain, Mandira Varma-Basil, Jyotirmoy Maity, M Thirumal, Ashok K Prasad
A series of β-d-ribofuranosyl coumarinyl-1,2,3-triazoles have been synthesized by Cu-catalyzed cycloaddition reaction between azidosugar and 7-O-/7-alkynylated coumarins in 62-70% overall yields. The in vitro antimycobacterial activity evaluation of the synthesized triazolo-conjugates against Mycobacterium tuberculosis revealed that compounds were bactericidal in nature and some of them were found to be more active than one of the first line antimycobacterial drug ethambutol against sensitive reference strain H37Rv, and 7 to 420 times more active than all four first line antimycobacterial drugs (isoniazid, rifampicin, ethambutol and streptomycin) against multidrug resistant clinical isolate 591...
February 27, 2018: European Journal of Medicinal Chemistry
Partosch Falko, Mielke Hans, Stahlmann Ralf, Gundert-Remy Ursula
Mycobacterial diseases remain a significant cause of morbidity and mortality worldwide. Rifampicin and ethambutol are among the drugs recommended by WHO as first line treatment. In this work, we addressed the question whether doses of the two anti-tuberculosis agents ethambutol and rifampicin transferred to a nursed infant could be of health concerns when the mother is under treatment. We used the approach of pharmacokinetic modelling using a structural model with two interconnected organisms, the first one being the organism of the nursing mother, the second one being the organism of the nursed child...
March 5, 2018: Basic & Clinical Pharmacology & Toxicology
Doreen Luedtke, Kristell Marzin, Arvid Jungnik, Ute von Wangenheim, Claudia Dallinger
BACKGROUND: Nintedanib is a substrate for p-glycoprotein which can impact bioavailability. We investigated the effects of ketoconazole, a p-glycoprotein inhibitor, and rifampicin, a p-glycoprotein inducer, on the pharmacokinetics of nintedanib. METHODS: In the ketoconazole study, 34 healthy subjects received nintedanib 50 mg orally alone and 1 h after the last dose of ketoconazole given orally at a dose of 400 mg once daily for 3 days in 1 of 2 randomized sequences...
March 2, 2018: European Journal of Drug Metabolism and Pharmacokinetics
Thijs H Oude Munnink, Anna Demmer, Roel H J Slenter, Kris L L Movig
The authors present a case of a 69-year-old man with arrhythmogenic right ventricular cardiomyopathy controlled with amiodarone and an infected orthopedic prosthesis requiring treatment with rifampicin. This combination involves a pharmacokinetic drug-drug interaction leading to subtherapeutic drug concentrations of amiodarone and its active metabolite. The long half-life of amiodarone and its active metabolite in combination with the late onset and offset of cytochrome P4503A (CYP3A4) induction by rifampicin makes this a challenging drug-drug interaction to cope with in clinical practice...
February 20, 2018: Therapeutic Drug Monitoring
Venkatesh Pilla Reddy, Michael Walker, Pradeep Sharma, Peter Ballard, Karthick Vishwanathan
Osimertinib is a potent, highly selective, irreversible inhibitor of Epidermal Growth Factor Receptor and T790M resistance mutation receptor. In vitro metabolism data suggested osimertinib is a substrate of CYP3A4/5, a weak inducer of CYP3A and an inhibitor of BCRP. A combination of in vitro data, clinical pharmacokinetic data and drug-drug interaction (DDI) data of osimertinib in oncology patients were used to develop the physiologically based pharmacokinetic (PBPK) model and verify the DDI data of osimertinib...
February 22, 2018: CPT: Pharmacometrics & Systems Pharmacology
Chao Chen, Susana Gardete, Robert Sander Jansen, Annanya Shetty, Thomas Dick, Kyu Y Rhee, Véronique Dartois
Mycobacterium tuberculosis (Mtb) kills more people than any other bacterial pathogen and is becoming increasingly untreatable due to the emergence of resistance. Verapamil, an FDA-approved calcium channel blocker, potentiates the effect of several anti-tuberculosis (TB) drugs in vitro and in vivo. This potentiation is widely attributed to inhibition of Mtb's efflux pumps, resulting in intrabacterial drug accumulation. Here, we confirm and quantify verapamil's synergy with several anti-TB drugs, including bedaquiline and clofazimine, but find that this effect is not due to increased intrabacterial drug accumulation...
February 20, 2018: Antimicrobial Agents and Chemotherapy
Lars Mizera, Tobias Geisler, Klaus Mörike, Meinrad Gawaz, Martin Steeg
The cytochrome P450 is a superfamily of isoenzymes that are responsible for the metabolism of many drugs. Significant changes in pharmacokinetics and drug interactions may be due to induction of hepatic cytochrome P450 enzymes. Rifampicin is a common inducer of CYP3A4. We report a case of a 57-year-old woman who was suspected for endocarditis and therefore treated with rifampicin. Due to previous mechanical aortic valve replacement, she also received phenprocoumon for anticoagulation. Although continuing anticoagulant therapy, antibiotic coadministration led to normal international normalised ratio (INR) level...
February 12, 2018: BMJ Case Reports
Karthick Vishwanathan, Paul A Dickinson, Karen So, Karen Thomas, Yuh-Min Chen, Javier De Castro Carpeño, Anne-Marie C Dingemans, Hye Ryun Kim, Joo-Hang Kim, Matthew G Krebs, James Chih-Hsin Yang, Khanh Bui, Doris Weilert, R Donald Harvey
AIMS: We investigated the effects of a strong CYP3A4 inhibitor (itraconazole) or inducer (rifampicin) on the pharmacokinetics of the epidermal growth factor receptor kinase inhibitor osimertinib, in patients with advanced non-small cell lung cancer in two phase I, open-label, two-part clinical studies. Part one of both studies is reported. METHODS: In the itraconazole study (NCT02157883), patients received single-dose osimertinib 80 mg on Days 1 and 10 and itraconazole (200 mg twice daily) on Days 6-18 orally...
January 30, 2018: British Journal of Clinical Pharmacology
Cristina El Haj, Oscar Murillo, Alba Ribera, Nuria Lloberas, Joan Gómez-Junyent, Fe Tubau, Pere Fontova, Carme Cabellos, Javier Ariza
BACKGROUND: Linezolid or cotrimoxazole plus rifampicin (RIF) are alternative oral treatments for staphylococcal prosthetic joint infections when fluoroquinolones are not possible to use, but there is limited evidence about its activity. OBJECTIVES: We evaluated the efficacy of linezolid (LZD) and cotrimoxazole (SXT) alone and in combination with RIF against Staphylococcus aureus in an in vitro pharmacokinetic/pharmacodynamic biofilm model. METHODS: Using the CDC Biofilm Reactor® system, simulated regimens of LZD (600 mg q12h), SXT (160/800 mg q8h) and levofloxacin (LVX, 750 mg/day) alone and in combination with RIF (600 mg/day) were evaluated against one MSSA and one MRSA strain...
January 25, 2018: International Journal of Antimicrobial Agents
Ryuta Asaumi, Kota Toshimoto, Yoshifusa Tobe, Kenta Hashizume, Ken-Ichi Nunoya, Haruo Imawaka, Wooin Lee, Yuichi Sugiyama
This study aimed to construct a physiologically based pharmacokinetic (PBPK) model of rifampicin that can accurately and quantitatively predict complex drug-drug interactions (DDIs) involving its saturable hepatic uptake and auto-induction. Using in silico and in vitro parameters, and reported clinical pharmacokinetic data, rifampicin PBPK model was built and relevant parameters for saturable hepatic uptake and UDP-glucuronosyltransferase auto-induction were optimized by fitting. The parameters for cytochrome P450 (CYP) 3A and CYP2C9 induction by rifampicin were similarly optimized using clinical DDI data with midazolam and tolbutamide as probe substrates, respectively...
January 25, 2018: CPT: Pharmacometrics & Systems Pharmacology
Yi-An Bi, Sumathy Mathialagan, Laurie Tylaska, Myra Fu, Julie Keefer, Anna Vildhede, Chester Costales, A David Rodrigues, Manthena Varma
Tolbutamide is primarily metabolized by cytochrome P450 (CYP)2C9, and thus, frequently applied as a clinical probe substrate for CYP2C9 activity. However, there is a marked discrepancy in the in vitro-in vivo extrapolation of its metabolic clearance implying potential for additional clearance mechanisms. The goal of this study was to evaluate the role of hepatic uptake transport in the pharmacokinetics of tolbutamide and identify the molecular mechanism thereof. Transport studies using singly-transfected cells expressing six major hepatic uptake transporters showed that tolbutamide is a substrate to organic anion transporter (OAT)2 alone -- with transporter affinity (Km) of 19...
January 11, 2018: Journal of Pharmacology and Experimental Therapeutics
Yasuhiro Uno, Shotaro Uehara, Hiroshi Yamazaki
Cynomolgus monkeys (Macaca fascicularis, Old World Monkeys) and common marmosets (Callithrix jacchus, New World Monkeys) have been widely, and expectedly, used as non-human primate models in drug development studies. Major drug-metabolizing cytochrome P450 (P450) enzymes information is now available that supports these primate species as animal models, and it is established that multiple forms of cynomolgus monkey and common marmoset P450 enzymes have generally similar substrate recognition functionality to human P450 enzymes...
December 22, 2017: Biochemical Pharmacology
Yingjun Liu, Henry Pertinez, Fatima Ortega-Muro, Laura Alameda-Martin, Thomas Harrison, Geraint Davies, Anthony Coates, Yanmin Hu
Objectives: Although high-dose rifampicin holds promise for improving tuberculosis disease control by eradication of persistent bacteria, the optimal dose of rifampicin that kills persistent bacteria and shortens the treatment duration is unknown. Methods: The Cornell mouse model was used to test the efficacy of rifampicin at elevated doses combined with isoniazid and pyrazinamide to kill actively growing and persistent bacilli and to measure relapse rate. Persistent bacteria were evaluated using Mycobacterium tuberculosis culture supernatant containing resuscitation-promoting factors...
December 12, 2017: Journal of Antimicrobial Chemotherapy
Shelby Barnett, Kayode Ogungbenro, Karelle Ménochet, Hong Shen, Yurong Lai, W Griffith Humphreys, Aleksandra Galetin
This study evaluates coproporphyrin I (CPI) as a selective endogenous biomarker of OATP1B-mediated drug-drug interactions (DDIs) relative to clinical probe rosuvastatin using nonlinear mixed-effect modelling. Plasma and urine CPI data in the presence/absence of rifampicin were modelled to describe CPI synthesis, elimination clearances and obtain rifampicin in vivo OATP Ki. The biomarker showed stable inter-occasion baseline concentrations and low inter-individual variability (<25%) in subjects with wild type SLCO1B1...
December 15, 2017: Clinical Pharmacology and Therapeutics
S Berlin, S Wallstabe, E Scheuch, S Oswald, M Hasan, D Wegner, M Grube, M Venner, A Ullrich, W Siegmund
BACKGROUND: Standard treatment of foals with severe abscessing lung infection caused by Rhodococcus equi using rifampicin and a macrolide antibiotic can be compromised by extensive inhibition and/or induction of drug metabolising enzymes (e.g. CYP3A4) and transport proteins (e.g. P-glycoprotein), as has been shown for rifampicin and clarithromycin. The combination of rifampicin with the new, poorly metabolised gamithromycin, a long-acting analogue of azithromycin and tulathromycin with lower pharmacokinetic interaction potential, might be a suitable alternative...
December 14, 2017: Equine Veterinary Journal
Ilaria Motta, Andrea Calcagno, Stefano Bonora
WHO global strategy is to end tuberculosis epidemic by 2035. Pharmacokinetic and pharmacogenetic studies are increasingly performed and might confirm their potential role in optimizing treatment outcome in specific settings and populations. Insufficient drug exposure seems to be a relevant factor in tuberculosis outcome and for the risk of phenotypic resistance. Areas covered: This review discusses available pharmacokinetic and pharmacogenetic data of first and second-line antitubercular agents in relation to efficacy and toxicity...
January 2018: Expert Opinion on Drug Metabolism & Toxicology
Simone H J van den Elsen, Lisette M Oostenbrink, Scott K Heysell, Daiki Hira, Daan J Touw, Onno W Akkerman, Mathieu S Bolhuis, Jan-Willem C Alffenaar
BACKGROUND: Therapeutic drug monitoring is useful in the treatment of tuberculosis to assure adequate exposure, minimize antibiotic resistance, and reduce toxicity. Salivary therapeutic drug monitoring could reduce the risks, burden, and costs of blood-based therapeutic drug monitoring. This systematic review compared human pharmacokinetics of anti-tuberculosis drugs in saliva and blood to determine if salivary therapeutic drug monitoring could be a promising alternative. METHODS: On December 2, 2016, PubMed and the Institute for Scientific Information Web of Knowledge were searched for pharmacokinetic studies reporting human salivary and blood concentrations of anti-tuberculosis drugs...
November 8, 2017: Therapeutic Drug Monitoring
Helen Gu, Catherine Dutreix, Sam Rebello, Taoufik Ouatas, Lai Wang, Dung Yu Chun, Heidi J Einolf, Handan He
Midostaurin (PKC412) is being investigated for the treatment of acute myeloid leukemia (AML) and advanced systemic mastocytosis (advSM). It is extensively metabolized by cytochrome P450 (CYP) 3A4 to form 2 major active metabolites, CGP52421 and CGP62221. In vitro and clinical drug-drug interaction (DDI) studies indicated that midostaurin and its metabolites are substrates, reversible and time-dependent inhibitors, and inducers of CYP3A4. A simultaneous pharmacokinetic model of parent and active metabolites was initially developed by incorporating data from in vitro, preclinical, and clinical pharmacokinetic studies in healthy volunteers and in patients with AML or advSM...
November 8, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
Aiqun Li, Karen Yeo, Devin Welty, Haojing Rong
BACKGROUND: Guanfacine extended-release (GXR) is an orally administered, non-stimulant treatment for children and adolescents with attention-deficit/hyperactivity disorder (ADHD) and is primarily metabolized by the 3A4 isozyme of cytochrome P450 (CYP3A4). The results of clinical pharmacokinetic (PK) studies indicate that guanfacine is sensitive to drug-drug interactions (DDIs) perpetrated by strong inhibitors and inducers of CYP3A4. OBJECTIVE: The aim was to provide guidance on the possible requirement for GXR dose adjustment in children and adolescents with ADHD by predicting DDIs following co-administration with moderate CYP3A4 inhibitors and inducers...
November 2, 2017: Paediatric Drugs
Tomohiro Kusawake, Martin den Adel, Dorien Groenendaal-van de Meent, Alberto Garcia-Hernandez, Akitsugu Takada, Kota Kato, Yoshiaki Ohtsu, Masataka Katashima
INTRODUCTION: Amenamevir is a nonnucleoside antiherpes virus compound available for treating herpes zoster infections. Four studies aimed to determine any potential interactions between amenamevir and ketoconazole, rifampicin, midazolam, or warfarin in healthy male participants. METHODS: Two studies were open-label studies that evaluated the effects of multiple doses of ketoconazole (400 mg) and rifampicin (600 mg) on the pharmacokinetics of a single oral dose of amenamevir...
November 2017: Advances in Therapy
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"