keyword
MENU ▼
Read by QxMD icon Read
search

Tacrolimus pharmacokinetics

keyword
https://www.readbyqxmd.com/read/29329497/pharmacokinetic-interactions-between-elbasvir-grazoprevir-and-immunosuppressant-drugs-in-healthy-volunteers
#1
Hwa-Ping Feng, Luzelena Caro, Christine M Fandozzi, Zifang Guo, Jennifer Talaty, Dennis Wolford, Deborah Panebianco, Marian Iwamoto, Joan R Butterton, Wendy W Yeh
Elbasvir (EBR)/grazoprevir (GZR) may be coadministered with immunosuppressant drugs in posttransplant people who are infected with hepatitis C virus. The aim of the present study was to assess the safety and pharmacokinetic interactions between EBR and GZR and single doses of cyclosporine, tacrolimus, mycophenolate mofetil (MMF), and prednisone. This was a 4-part, open-label study in 58 healthy volunteers. Participants received single doses of cyclosporine 400 mg, tacrolimus 2 mg, MMF 1 g, or prednisone 40 mg alone or in the presence of once-daily EBR 50 mg/GZR 200 mg...
January 12, 2018: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29329489/mycophenolic-acid-and-its-metabolites-in-kidney-transplant-recipients-a-semimechanistic-enterohepatic-circulation-model-to-improve-estimating-exposure
#2
Malek Okour, Pamala A Jacobson, Mariam A Ahmed, Ajay K Israni, Richard C Brundage
Mycophenolic acid (MPA) is an approved immunosuppressive agent widely prescribed to prevent rejection after kidney transplantation. Wide between-subject variability (BSV) in MPA exposure exists which in part may be due to variability in enterohepatic recirculation (EHC). Several modeling strategies were developed to evaluate EHC as part of MPA pharmacokinetics, however mechanistic representation of EHC is limited. These models have not provided a satisfactory representation of the physiology of EHC in their modeling assumptions...
January 12, 2018: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29315140/high-intrapatient-variability-of-tacrolimus-exposure-in-the-early-period-after-liver-transplantation-is-associated-with-poorer-outcomes
#3
Michel Rayar, Camille Tron, Caroline Jézéquel, Jean Marie Beaurepaire, Antoine Petitcollin, Pauline Houssel-Debry, Christophe Camus, Marie Clémence Verdier, Ammar Dehlawi, Mohamed Lakéhal, Véronique Desfourneaux, Bernard Meunier, Laurent Sulpice, Eric Bellissant, Karim Boudjema, Florian Lemaitre
BACKGROUND: Tacrolimus (TAC) is the cornerstone of immunosuppressive regimen in liver transplantation (LT). Its pharmacokinetics is characterized by a high inter- and intrapatient variability leading to an unpredictable dose-response relationship. The aim of our study was to evaluate the impact of TAC intrapatient variability (IPV) on graft and patient outcomes after liver transplantation. METHODS: We retrospectively analyzed 812 LT recipients treated with TAC. The IPV of TAC concentrations was estimated by calculating the coefficient of variation (CV) of whole blood trough concentrations...
January 8, 2018: Transplantation
https://www.readbyqxmd.com/read/29298646/tacrolimus-pharmacokinetic-considerations-for-clinicians
#4
Katharina Schutte-Nutgen, Gerold Tholking, Barbara Suwelack, Stefan Reuter
The calcineurin inhibitor tacrolimus (Tac) is an integral part of the standard immunosuppressive regimen after renal transplantation (RTx). However, clinical management of Tac therapy can be challenging because of its narrow therapeutic window and because many factors interfere with its metabolism. Therefore, therapeutic drug monitoring is used to adjust the dosage. Recently, we were able to classify patients receiving tacrolimus into two major metabolism groups by simple calculation of the C/D ratio (expressed as the blood concentration normalized by the dose)...
December 31, 2017: Current Drug Metabolism
https://www.readbyqxmd.com/read/29289674/investigating-the-impact-of-drug-crystallinity-in-amorphous-tacrolimus-capsules-on-pharmacokinetics-and-bioequivalence-using-discriminatory-in-vitro-dissolution-testing-and-pbpk-modeling-and-simulation
#5
Hitesh S Purohit, Niraj S Trasi, Dajun D Sun, Edwin C Y Chow, Hong Wen, Xinyuan Zhang, Yi Gao, Lynne S Taylor
Delivering a drug in amorphous form in a formulated product is a strategy used to enhance the apparent solubility of a drug substance and its oral bioavailability. Drug crystallization in such products may occur during the manufacturing process or upon storage, reducing the solubility advantage of the amorphous drug. However, the impact of partial drug crystallization in the drug product on the resulting bioavailability and pharmacokinetics is unknown. In this study, dissolution testing of commercial tacrolimus capsules (which are formulated to contain amorphous drug), both fresh and those containing different amounts of crystalline drug, was conducted using both USP and non-compendial dissolution tests with different dissolution media and volumes...
December 28, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29277665/tacrolimus-an-updated-review-on-delivering-strategies-for-multifarious-diseases
#6
REVIEW
Divya Dheer, Jyoti, Prem N Gupta, Ravi Shankar
From the current trends, tacrolimus (TAC) has become an important therapeutic option for the optimal individualization of immunosuppressive therapy especially in case of transplant recipients. TAC is used most frequently in comparison to other immunosuppressants because it offers better safety profile with increased long-term survival in patients especially in children and adolescents. This drug has developed an immense interest in the research field owing to its potential pharmacological scope but due to its poor water solubility, need of concomitant steroids and higher incidences of nephrotoxicity, there comes a need for future research to minimize such limitations and decipher maximum use of the drug...
December 22, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29277422/formulation-and-in-vivo-pharmacokinetic-evaluation-of-ethyl-cellulose-coated-sustained-release-multiple-unit-system-of-tacrolimus
#7
Taek Hwan Shin, Myoung Jin Ho, Sung Rae Kim, Sung Hyun Im, Chang Hyun Kim, Sangkil Lee, Myung Joo Kang, Young Wook Choi
A novel once-a-day sustained-release (SR) system of tacrolimus (FK506), a poorly water-soluble immunosuppressive agent, was designed employing ethyl cellulose (EC) polymer as release retardant. Drug (5 mg) was layered onto sugar spheres (518.3 mg) with hypromellose (5 mg), to transform the drug from a crystalline to an amorphous form. Subsequently, the drug-layered pellets were recoated with EC polymer (0.5-1.5 mg) using a fluid bed granulator. Drug release from the reservoir-type pellets was markedly impeded by the outer EC-based coating layer (EC 1 mg), displaying about 60% of drug release after 8 h, regardless of the acidity of the media...
December 22, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29229354/comparative-clinical-trial-of-the-variability-factors-of-the-exposure-indices-used-for-the-drug-monitoring-of-two-tacrolimus-formulations-in-kidney-transplant-recipients
#8
Pierre Marquet, Laetitia Albano, Jean-Baptiste Woillard, Lionel Rostaing, Nassim Kamar, Charlotte Sakarovitch, Philippe Gatault, Matthias Buchler, Bernard Charpentier, Eric Thervet, Elisabeth Cassuto
BACKGROUND: Several studies found differences in tacrolimus whole blood trough levels (C0) or area-under-the curve (AUC) between the twice-daily (Tac-BID) and once-daily (Tac-OD) formulations given to kidney transplant recipients at equal doses. As C0 is widely used as a surrogate of the AUC for individual dose adjustment, this study investigated the correlation and proportionality between C0 and the 24h-AUC, depending on the formulation, time post-transplantation, pharmacogenetics traits and other individual characteristics...
December 8, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/29222025/preparation-and-comparison-of-tacrolimus-loaded-solid-dispersion-and-self-microemulsifying-drug-delivery-system-by-in-vitro-in-vivo-evaluation
#9
Taotao Huo, Chun Tao, Minxin Zhang, Qinghong Liu, Bing Lin, Zhihong Liu, Jialiang Zhang, Meijing Zhang, Haiyue Yang, Jue Wu, Xinrong Sun, Qian Zhang, Hongtao Song
This study aimed to compare the dissolution and the intestinal absorption of tacrolimus in self-microemulsifying drug delivery system (SMEDDS) and solid dispersion (SD). Poloxamer 188 SD was prepared by the combination of the solvent evaporation method and the freeze drying method. Hydroxypropyl methylcellulose (HPMC) SD was prepared by the solvent evaporation method combined with the vacuum drying method. The formation of SD was confirmed by SEM images which showed new solid phases. The SMEDDS was composed of oil (Labrafil M1944 CS 28%), surfactant (Cremophor EL 48%) and co-surfactant (Transcutol P 24%)...
December 5, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29206086/early-use-of-tacrolimus-extended-release-in-a-pediatric-kidney-transplant-recipient
#10
Kristen R Szempruch, Katherine D Westreich, Alexander H Toledo
Tacrolimus extended-release pharmacokinetics and its once-daily formulation provide beneficial properties, and its use has been evaluated in the adult kidney transplant population. Here, we report a case of successful conversion from tacrolimus immediate-release capsules to tacrolimus extended-release tablets in a pediatric kidney transplant recipient.
December 5, 2017: Experimental and Clinical Transplantation
https://www.readbyqxmd.com/read/29199543/genetic-variations-of-the-xenoreceptors-nr1i2-and-nr1i3-and-their-effect-on-drug-disposition-and-response-variability
#11
Litaty Céphanoée Mbatchi, Jean-Paul Brouillet, Alexandre Evrard
NR1I2 (PXR) and NR1I3 (CAR) are nuclear receptors that are classified as xenoreceptors. Upon activation by various xenobiotics, including marketed drugs, they regulate the transcription level of major drug-metabolizing enzymes and transporters and facilitate the elimination of xenobiotics from the body. The modulation of the activity of these two xenoreceptors by various ligands is a major source of pharmacokinetic variability of environmental origin. NR1I2 and NR1I3 genetic polymorphisms can affect the pharmacokinetics and therapeutic response to many drugs, such as irinotecan, tacrolimus and atazanavir...
December 4, 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/29177199/predicting-tacrolimus-concentrations-in-children-receiving-a-heart-transplant-using-a-population-pharmacokinetic-model
#12
Joseph E Rower, Chris Stockmann, Matthew W Linakis, Shaun S Kumar, Xiaoxi Liu, E Kent Korgenski, Catherine M T Sherwin, Kimberly M Molina
Objective: Immunosuppressant therapy plays a pivotal role in transplant success and longevity. Tacrolimus, a primary immunosuppressive agent, is well known to exhibit significant pharmacological interpatient and intrapatient variability. This variability necessitates the collection of serial trough concentrations to ensure that the drug remains within therapeutic range. The objective of this study was to build a population pharmacokinetic (PK) model and use it to determine the minimum number of trough samples needed to guide the prediction of an individual's future concentrations...
2017: BMJ Paediatrics Open
https://www.readbyqxmd.com/read/29162334/results-of-asertaa-a-randomized-prospective-crossover-pharmacogenetic-study-of-immediate-release-versus-extended-release-tacrolimus-in-african-american-kidney-transplant-recipients
#13
Jennifer Trofe-Clark, Daniel C Brennan, Patricia West-Thielke, Michael C Milone, Mary Ann Lim, Robin Neubauer, Vincenza Nigro, Roy D Bloom
BACKGROUND: Differences in tacrolimus dosing across ancestries is partly attributable to polymorphisms in CYP3A5 genes that encode tacrolimus-metabolizing cytochrome P450 3A5 enzymes. The CYP3A5*1 allele, preponderant in African Americans, is associated with rapid metabolism, subtherapeutic concentrations, and higher dose requirements for tacrolimus, all contributing to worse outcomes. Little is known about the relationship between CYP3A5 genotype and the tacrolimus pharmacokinetic area under the curve (AUC) profile in African Americans or whether pharmacogenetic differences exist between conventional twice-daily, rapidly absorbed, immediate-release tacrolimus (IR-Tac) and once-daily extended-release tacrolimus (LifeCycle Pharma Tac [LCPT]) with a delayed absorption profile...
November 18, 2017: American Journal of Kidney Diseases: the Official Journal of the National Kidney Foundation
https://www.readbyqxmd.com/read/29160300/genome-wide-association-study-identifies-the-common-variants-in-cyp3a4-and-cyp3a5-responsible-for-variation-in-tacrolimus-trough-concentration-in-caucasian-kidney-transplant-recipients
#14
W S Oetting, B Wu, D P Schladt, W Guan, R P Remmel, R B Mannon, A J Matas, A K Israni, P A Jacobson
The immunosuppressant tacrolimus (TAC) is metabolized by both cytochrome P450 3A4 (CYP3A4) and CYP3A5 enzymes. It is common for European Americans (EA) to carry two CYP3A5 loss-of-function (LoF) variants that profoundly reduces TAC metabolism. Despite having two LoF alleles, there is still considerable variability in TAC troughs and identifying additional variants in genes outside of the CYP3A5 gene could provide insight into this variability. We analyzed TAC trough concentrations in 1345 adult EA recipients with two CYP3A5 LoF alleles in a genome-wide association study...
November 21, 2017: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/29159710/prediction-of-free-from-total-mycophenolic-acid-concentrations-in-stable-renal-transplant-patients-a-population-based-approach
#15
Helena Colom, Franc Andreu, Teun van Gelder, Dennis A Hesselink, Brenda C M de Winter, Oriol Bestard, Joan Torras, Josep M Cruzado, Josep M Grinyó, Núria Lloberas
BACKGROUND: A population pharmacokinetic (PK) protein-binding model was developed to (1) predict free mycophenolic acid (fMPA) based on total MPA (tMPA) concentrations in renal transplant patients, to establish the therapeutic range of fMPA through pharmacokinetic-pharmacodynamic studies; and (2) provide a guideline for dosing mycophenolate mofetil (MMF). METHODS: Full PK profiles of 56 patients (from five different occasions) during the first year after transplantation who were treated with oral MMF and cyclosporine, or macrolides (either tacrolimus or sirolimus), were analysed...
November 20, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/29135993/bioequivalence-between-innovator-and-generic-tacrolimus-in-liver-and-kidney-transplant-recipients-a-randomized-crossover-clinical-trial
#16
Rita R Alloway, Alexander A Vinks, Tsuyoshi Fukuda, Tomoyuki Mizuno, Eileen C King, Yuanshu Zou, Wenlei Jiang, E Steve Woodle, Simon Tremblay, Jelena Klawitter, Jost Klawitter, Uwe Christians
BACKGROUND: Although the generic drug approval process has a long-term successful track record, concerns remain for approval of narrow therapeutic index generic immunosuppressants, such as tacrolimus, in transplant recipients. Several professional transplant societies and publications have generated skepticism of the generic approval process. Three major areas of concern are that the pharmacokinetic properties of generic products and the innovator (that is, "brand") product in healthy volunteers may not reflect those in transplant recipients, bioequivalence between generic and innovator may not ensure bioequivalence between generics, and high-risk patients may have specific bioequivalence concerns...
November 2017: PLoS Medicine
https://www.readbyqxmd.com/read/29123208/differential-t-cell-signaling-pathway-activation-by-tacrolimus-and-belatacept-after-kidney-transplantation-post-hoc-analysis-of-a-randomised-controlled-trial
#17
Nynke M Kannegieter, Dennis A Hesselink, Marjolein Dieterich, Gretchen N de Graav, Rens Kraaijeveld, Carla C Baan
Pharmacokinetic immunosuppressive drug monitoring poorly correlates with clinical outcomes after solid organ transplantation. A promising method for pharmacodynamic monitoring of tacrolimus (TAC) in T cell subsets of transplant recipients might be the measurement of (phosphorylated) p38MAPK, ERK1/2 and Akt (activated downstream of the T cell receptor) by phospho-specific flow cytometry. Here, blood samples from n = 40 kidney transplant recipients (treated with either TAC-based or belatacept (BELA)-based immunosuppressive drug therapy) were monitored before and throughout the first year after transplantation...
November 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29110351/posaconazole-liquid-vs-tablet-formulation-in-lung-transplant-recipients
#18
D Telzer, A Weber, F Ihle, S Matthes, F Ceelen, G Zimmermann, N Kneidinger, R Schramm, H Winter, M Zoller, M Vogeser, J Behr, C Neurohr
BACKGROUND: Posaconazole is an extended-spectrum triazole antifungal used in the treatment and prophylaxis of Aspergillus infections. It is available as oral suspension (POS-Liq) and delayed-release tablets (POS-Tab). OBJECTIVES: The aim of this longitudinal, retrospective study was to compare the clinical effectiveness, toxicity, and pharmacokinetics of POS-Liq vs. POS-Tab in lung transplant recipients (LTx-recipients), who were treated with both formulations subsequently...
November 6, 2017: Mycoses
https://www.readbyqxmd.com/read/29095105/genotype-based-tacrolimus-dosing-guidelines-with-or-without-cyp3a4-22
#19
Laure Elens, Vincent Haufroid
AIM: To test the relevance of revisiting the genotype classification based on CYP3A5*3 solely by incorporating CYP3A4*22 information. METHODS: Discriminant analysis of principal component was performed to evaluate the relevance of either the CYP3A (CYP3A5 + CYP3A4 genotypes) or CYP3A5*3 classification variables. This analysis was based on a linear combination of noncompartmental pharmacokinetics parameters. RESULTS: Discriminant analysis of principal component gave better results with CYP3A compared with CYP3A5*3 clustering...
November 2, 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/29050276/a-new-donors-cyp3a5-and-recipients-cyp3a4-cluster-predicting-tacrolimus-disposition-and-new-onset-hypertension-in-chinese-liver-transplant-patients
#20
Yuan Liu, Tao Zhang, Xiaoqing Zhang, Ling Ye, Haitao Gu, Lin Zhong, Hongcheng Sun, Chenlong Song, Zhihai Peng, Junwei Fan
AIM: The purpose of the current study was to investigate individualized therapy of tacrolimus (Tac), as well as complications after liver transplantation (LT) with the known genetic determinants and clinical factors. METHODS: In this retrospective study, two cohorts (n=170) from the China Liver Transplant Registry (CLTR) database from July 2007 to March 2015 were included. RESULTS: Both donors' CYP3A5*3 and recipients' CYP3A4*1G had a correlation with Tac pharmacokinetics at four weeks (all P<0...
September 19, 2017: Oncotarget
keyword
keyword
55251
1
2
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"