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Tacrolimus pharmacokinetics

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https://www.readbyqxmd.com/read/28540692/effects-of-cyp3a5-polymorphisms-on-tacrolimus-pharmacokinetics-in-pediatric-kidney-transplantation-a-systematic-review-and-meta-analysis-of-observational-studies
#1
Yi-Ping Zong, Zi-Jie Wang, Wan-Li Zhou, Wei-Min Zhou, Tie-Liang Ma, Zheng-Kai Huang, Chun-Chun Zhao, Zhen Xu, Ruo-Yun Tan, Min Gu
BACKGROUND: CYP3A5 genetic polymorphisms have been reported to be strongly associated with the tacrolimus pharmacokinetics in adult kidney transplantation. However, there is no published meta-analysis in the influence of CYP3A5 variants on the requirements of the tacrolimus dose in pediatric renal-transplant recipients (RTRs). We wished to determine the effects of CYP3A5 polymorphisms on tacrolimus pharmacokinetics in pediatric RTRs. METHODS: A literature search was conducted to include relevant articles by searching PubMed, EMBASE and the Cochrane Central Register of Controlled Trials...
May 24, 2017: World Journal of Pediatrics: WJP
https://www.readbyqxmd.com/read/28540172/nonlinear-relationship-between-enteric-coated-mycophenolate-sodium-dose-and-mycophenolic-acid-exposure-in-han-kidney-transplantation-recipients
#2
Jun Zhang, Mengmeng Jia, Lihua Zuo, Na Li, Yonggang Luo, Zhi Sun, Xiaojian Zhang, Zhenfeng Zhu
The aim of the research was to investigate the pharmacokinetics (PK) of enteric-coated mycophenolate sodium (EC-MPS) by quantification of the active metabolite of mycophenolic acid (MPA) after multiple escalating oral doses in Han kidney transplant recipients. A total of 28 Han postoperative kidney transplant recipients were given a multiple-dose of 540, 720 or 900 mg of EC-MPS two times a day in combination with tacrolimus for 6 days. Blood specimens were collected at each time point from 0 to 12 h after EC-MPS administration...
May 2017: Acta Pharmaceutica Sinica. B
https://www.readbyqxmd.com/read/28474821/application-of-physiologically-based-pharmacokinetic-modeling-to-predict-drug-disposition-in-pregnant-populations
#3
Vamshi Krishna Jogiraju, Suvarchala Avvari, Rakesh Gollen, David R Taft
Pregnancy is associated with numerous physiologic changes that influence absorption, distribution, metabolism and excretion. Moreover, the magnitude of these effects changes as pregnancy matures. For most medications, there is limited information available about changes in drug disposition that can occur in pregnant patients, yet most women are prescribed one or more medications during pregnancy. In this investigation, PBPK modeling was used to assess the impact of pregnancy on the pharmacokinetic profiles of three medications (metformin, tacrolimus, oseltamivir) using the Simcyp® Simulator...
May 5, 2017: Biopharmaceutics & Drug Disposition
https://www.readbyqxmd.com/read/28469859/drug-interaction-between-tacrolimus-and-nilotinib-in-a-patient-with-chronic-myeloid-leukemia-after-renal-transplant
#4
Takashi Onaka, Naoto Takahashi, Masatomo Miura, Akihito Yonezawa
Nilotinib, a BCR-ABL tyrosine kinase inhibitor, is a known inhibitor of CYP3A4 and could increase the concentration of drugs metabolized by CYP3A4. An immunosuppressive drug for nilotinib-treated patients following transplant should be administered with careful pharmacokinetic monitoring because of its interaction with nilotinib.
May 2017: Clinical Case Reports
https://www.readbyqxmd.com/read/28437851/fexofenadine-a-putative-in-vivo-p-glycoprotein-probe-fails-to-predict-clearance-of-the-substrate-tacrolimus-in-renal-recipients
#5
Thomas Vanhove, Thomas Bouillon, Henriëtte de Loor, Pieter Annaert, Dirk R J Kuypers
Whether combined use of probe drugs for CYP3A4 and P-glycoprotein can clarify the relative contribution of these proteins to pharmacokinetic variability of a dual substrate like tacrolimus has never been assessed. Seventy renal recipients underwent simultaneous 8-hour pharmacokinetic profiles for tacrolimus, the CYP3A4 probe midazolam and the putative P-glycoprotein probe fexofenadine. Patients were genotyped for polymorphisms in CYP3A5, CYP3A4, ABCB1, ABCC2 and SLCO2B1, -1B1 and 1B3. Carriers of the ABCB1 2677G>A polymorphism displayed lower fexofenadine Cmax (-66%; P=0...
April 24, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28407449/drug-interactions-and-safety-profiles-with-concomitant-use-of-caspofungin-and-calcineurin-inhibitors-in-allogeneic-haematopoietic-cell-transplantation
#6
Mitsutaka Nishimoto, Hideo Koh, Atsushi Tokuwame, Yosuke Makuuchi, Masatomo Kuno, Teruhito Takakuwa, Hiroshi Okamura, Shiro Koh, Takuro Yoshimura, Satoru Nanno, Mika Nakamae, Asao Hirose, Yasuhiro Nakashima, Takahiko Nakane, Masayuki Hino, Hirohisa Nakamae
AIM: Small-scale clinical studies have reported on drug interactions between caspofungin (CPFG) and calcineurin inhibitors in healthy subjects; however, little is known about these interactions in allogeneic haematopoietic cell transplantation (allo-HCT) patients. METHODS: We retrospectively assessed the drug interactions and safety profiles in allo-HCT recipients treated concomitantly with CPFG and calcineurin inhibitors. RESULTS: Ninety-one consecutive cases were evaluated...
April 13, 2017: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28401703/tacrolimus-population-pharmacokinetics-according-to-cyp3a5-genotype-and-clinical-factors-in-chinese-adult-kidney-transplant-recipients
#7
REVIEW
H J Zhang, D Y Li, H J Zhu, Y Fang, T S Liu
WHAT IS KNOWN AND OBJECTIVES: Tacrolimus is characterized by a narrow therapeutic index and a considerable inter- and intraindividual pharmacokinetic variability. The aim of our study was to develop a population pharmacokinetic model of tacrolimus in adult kidney transplant of Chinese patients, identify factors especially CYP3A5*3 genetic polymorphism that explain variability, and determine dosage regimens. METHODS: Pharmacogenomic data obtained from 83 Chinese kidney transplant patients treated with tacrolimus were determined using polymerase chain reaction-restriction fragment length polymorphism analysis...
April 11, 2017: Journal of Clinical Pharmacy and Therapeutics
https://www.readbyqxmd.com/read/28389935/population-pharmacokinetics-and-bayesian-estimators-for-refined-dose-adjustment-of-a-new-tacrolimus-formulation-in-kidney-and-liver-transplant-patients
#8
Jean-Baptiste Woillard, Jean Debord, Caroline Monchaud, Franck Saint-Marcoux, Pierre Marquet
BACKGROUND AND OBJECTIVES: A new once-daily formulation of tacrolimus (Envarsus(®)) has recently been developed, with alleged different pharmacokinetics from previous tacrolimus formulations. The objectives of this study were to develop population pharmacokinetic models and Bayesian estimators based on limited sampling strategies for Envarsus(®) in kidney and liver transplant recipients. MATERIALS AND METHODS: Full tacrolimus concentration-time profiles (13 samples) were drawn from 57 liver (113 profiles) and 49 kidney (97 profiles) graft recipients transplanted for at least 6 months and switched from Prograf(®) to Envarsus(®)...
April 8, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/28377389/relative-bioavailability-of-single-doses-of-prolonged-release-tacrolimus-administered-as-a-suspension-orally-or-via-a-nasogastric-tube-compared-with-intact-capsules-a-phase-1-study-in-healthy-participants
#9
Nasrullah Undre, James Dickinson
OBJECTIVE: Tacrolimus, an immunosuppressant widely used in solid organ transplantation, is available as a prolonged-release capsule for once-daily oral administration. In the immediate postsurgical period, if patients cannot take intact capsules orally, tacrolimus therapy is often initiated as a suspension of the capsule contents, delivered orally or via a nasogastric tube. This study evaluated the relative bioavailability of prolonged-release tacrolimus suspension versus intact capsules in healthy participants...
April 4, 2017: BMJ Open
https://www.readbyqxmd.com/read/28343273/pharmacokinetic-comparison-of-cyclosporin-a-and-tacrolimus-in-graft-versus-host-disease-prophylaxis
#10
Ivan Sergeevich Moiseev, Ekaterina Andreevna Burmina, Albert Radikovich Muslimov, Olga Vladislavovna Pirogova, Sergey Nikolaevich Bondarenko, Elena Igorevna Darskaya, Yuliya Alexandrovna Tarakanova, Nadegda Georgievna Senina, Boris Vladimirovich Afanasyev
A number of studies were published with contradictory results comparing tacrolimus (Tac) and cyclosporine A (CsA) for graft-versus-host disease (GVHD) prophylaxis, but there are only few that accounted for pharmacokinetic (PK) parameters. In this study, we created a model based on median concentrations, variability of concentrations, and failures to maintain target levels that distinguished patients with low, intermediate, and high risks of acute GVHD (hazard ratios (HR) 1.77, 95%CI 1.36-2.32, p < 0.0001)...
March 25, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28342282/pharmacokinetic-and-pharmacogenetic-analysis-of-immunosuppressive-agents-after-laparoscopic-sleeve-gastrectomy
#11
Tayyab S Diwan, Alicia B Lichvar, Abbie D Leino, Alexander A Vinks, Uwe Christians, Adele R Shields, Michael A Cardi, Tsuyoshi Fukuda, Tomoyuki Mizuno, Tiffany Kaiser, E Steve Woodle, Rita R Alloway
BACKGROUND: Severe obesity has been shown to limit access to renal transplantation in patients with end-stage renal disease (ESRD). Laparoscopic sleeve gastrectomy (LSG) has been performed in the ESRD population to assist in achieving waitlist and transplant eligibility. Little is known about how LSG impacts the bioequivalence of tacrolimus products and immunosuppression pharmacokinetics. METHODS: This was a prospective, open-label, single-dose, crossover, two-period pharmacokinetic (PK) study...
March 25, 2017: Clinical Transplantation
https://www.readbyqxmd.com/read/28340819/influence-of-proton-pump-inhibitors-on-mycophenolic-acid-pharmacokinetics-in-patients-with-renal-transplantation-and-the-relationship-with-cytochrome-2c19-gene-polymorphism
#12
H S Ciftci, M S Karadeniz, T Tefik, Y Caliskan, H Yazıcı, E Demir, A Turkmen, I Nane, F S Oguz, F Aydin
BACKGROUND: Most patients have serious digestive complications after renal transplantation. Therefore, it is important to protect gastrointestinal function to improve the survival rate of transplant patients. Proton pump inhibitors (PPIs) such as lansoprazole and rabeprazole are widely administered to renal transplant patients with mycophenolic acid (MPA) in the perioperative period. PPIs are metabolized by cytochrome (CYP) 2C19 enzymes. Mycophenolate sodium (MYF) and mycophenolate mofetil (MMF) have been used in immunosuppression...
April 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28295849/efficacy-safety-and-pharmacokinetics-of-simeprevir-daclatasvir-and-ribavirin-in-patients-with-recurrent-hepatitis-c-virus-genotype-1b-infection-after-orthotopic-liver-transplantation-the-phase-ii-saturn-study
#13
Xavier Forns, Marina Berenguer, Kerstin Herzer, Martina Sterneck, Maria Francesca Donato, Pietro Andreone, Stefano Fagiuoli, Tomasz Cieciura, Magdalena Durlik, Jose Luis Calleja, Zoe Mariño, Umesh Shukla, Thierry Verbinnen, Oliver Lenz, Sivi Ouwerkerk-Mahadevan, Monika Peeters, Katrien Janssen, Ronald Kalmeijer, Wolfgang Jessner
BACKGROUND: Recurrent hepatitis C virus (HCV) infection following liver transplantation is associated with accelerated progression to graft failure and reduced patient survival. METHODS: The Phase II, open-label SATURN study (NCT01938625) investigated the combination of simeprevir (SMV), daclatasvir (DCV), and ribavirin (RBV) administered for 24 weeks in 35 patients with recurrent HCV genotype (GT) 1b infection after orthotopic liver transplantation (OLT). RESULTS: High rates of both on-treatment and sustained virologic response 12 weeks after end of treatment (SVR12) were achieved in patients who were either treatment-naïve or had failed post-OLT treatment with peginterferon and RBV...
March 13, 2017: Transplant Infectious Disease: An Official Journal of the Transplantation Society
https://www.readbyqxmd.com/read/28295581/pharmacokinetics-of-prolonged-release-tacrolimus-versus-immediate-release-tacrolimus-in-de-novo-liver-transplantation-a-randomized-phase-iii-sub-study
#14
Bo-Göran Ericzon, Evaristo Varo, Pavel Trunečka, Lutz Fischer, Michele Colledan, Bruno Gridelli, Andrés Valdivieso, John O'Grady, James Dickinson, Nasrullah Undre
BACKGROUND: With the same dose of tacrolimus, lower systemic exposure on the first day of dosing has been reported for prolonged-release tacrolimus compared with immediate-release tacrolimus, prompting investigation of differing initial doses. METHODS: This sub-study of a double-blind, randomized, phase III trial in de novo liver transplant recipients compared the pharmacokinetics of once-daily prolonged-release tacrolimus (initial dose: 0.2mg/kg/day) versus twice-daily immediate-release tacrolimus (initial dose: 0...
March 12, 2017: Clinical Transplantation
https://www.readbyqxmd.com/read/28280692/influence-of-tacrolimus-metabolism-rate-on-renal-function-after-solid-organ-transplantation
#15
REVIEW
Gerold Thölking, Hans Ulrich Gerth, Katharina Schuette-Nuetgen, Stefan Reuter
The calcineurin inhibitor (CNI) tacrolimus (TAC) is an integral part of the immunosuppressive regimen after solid organ transplantation. Although TAC is very effective in prevention of acute rejection episodes, its highly variable pharmacokinetic and narrow therapeutic window require frequent monitoring of drug levels and dose adjustments. TAC can cause CNI nephrotoxicity even at low blood trough levels (4-6 ng/mL). Thus, other factors besides the TAC trough level might contribute to CNI-related kidney injury...
February 24, 2017: World Journal of Transplantation
https://www.readbyqxmd.com/read/28246425/influence-of-il-18-and-il-10-polymorphisms-on-tacrolimus-elimination-in-chinese-lung-transplant-patients
#16
Xiaoqing Zhang, Jiandong Xu, Junwei Fan, Tao Zhang, Yuping Li, Boxiong Xie, Wei Zhang, Shengtao Lin, Ling Ye, Yuan Liu, Gening Jiang
Aims. The influence of interleukin-10 (IL-10) and interleukin-18 (IL-18) polymorphisms on tacrolimus pharmacokinetics had been described in liver and kidney transplantation. The expression of cytokines varied in different kinds of transplantation. The influence of IL-10 and IL-18 genetic polymorphisms on the pharmacokinetic parameters of tacrolimus remains unclear in lung transplantation. Methods. 51 lung transplant patients at Shanghai Pulmonary Hospital were included. IL-18 polymorphisms (rs5744247 and rs1946518), IL-10 polymorphisms (rs1800896, rs1800872, and rs3021097), and CYP3A5 rs776746 were genotyped...
2017: Disease Markers
https://www.readbyqxmd.com/read/28229376/the-pharmacogenetics-of-tacrolimus-in-corticosteroid-sparse-pediatric-and-adult-kidney-transplant-recipients
#17
Mads Juul Madsen, Troels K Bergmann, Kim Brøsen, Helle Charlotte Thiesson
INTRODUCTION: Tacrolimus is a calcineurin inhibitor used as an immunosuppressant drug in solid organ transplantation, and is mainly metabolized by cytochrome P450 (CYP) 3A4 and CYP3A5. Studies have shown an association between the CYP3A5 genotype and tacrolimus dose-adjusted trough concentrations. Variants in the genes PPARA, POR and CYP3A4 have recently been shown to influence tacrolimus metabolism. Furthermore, pharmacokinetic interaction between corticosteroid treatment and tacrolimus has been shown...
June 2017: Drugs in R&D
https://www.readbyqxmd.com/read/28214069/-pharmacokinetic-drug-interaction-between-miconazole-mucoadhesive-tablet-and-tacrolimus-about-3%C3%A2-case-reports-in-transplant-patients
#18
Marion Lepelley, Sophie Logerot, Xavier Fonrose, Céline Villier
Loramyc(®) is a mucoadhesive tablet of miconazole, indicated for the treatment of oropharyngeal candidiasis in immunocompromised patients. Miconazole, as others azole antifungals, is known for its potent inhibitory properties of cytochromes P450 enzymes and P-glycoprotein (P-gp). Inhibition of cytochromes P450 enzymes and P-gp can produce pharmacokinetic drug interaction. Immunosuppressive agents, such as calcineurin inhibitors (tacrolimus, cyclosporine) are substrates of cytochromes P450 3A4 and P-gp. Nevertheless, the impact of systemic absorption of miconazole mucoadhesive tablet has not been investigated by the laboratory before regulatory approval...
January 12, 2017: Thérapie
https://www.readbyqxmd.com/read/28185946/decreased-tacrolimus-plasma-concentrations-during-hcv-therapy-a-drug-drug-interaction-or-is-there-an-alternative-explanation
#19
E J Smolders, S Pape, C T M M de Kanter, A P van den Berg, J P H Drenth, D M Burger
Chronic hepatitis C virus (HCV) infection can cause severe liver cirrhosis, for which liver transplantation is the only therapy. To prevent organ rejection, transplanted patients are treated with immunosuppressive agents. We describe two transplanted patients treated with tacrolimus who were simultaneously treated with direct-acting antivirals (DAAs) for their chronic HCV infection. No pharmacokinetic drug-drug interactions (DDIs) were expected between tacrolimus and the selected DAAs. However, in both patients, tacrolimus plasma concentrations decreased during HCV treatment...
March 2017: International Journal of Antimicrobial Agents
https://www.readbyqxmd.com/read/28164520/the-effect-of-abcb1-polymorphisms-on-serial-tacrolimus-concentrations-in-stable-austrian-long-term-kidney-transplant-recipients
#20
Markus Riegersperger, Max Plischke, Corinna Steinhauser, Anita Jallitsch-Halper, Guerkan Sengoelge, Wolfgang C Winkelmayer, Gere Sunder-Plassmann, Manuela Födinger
BACKGROUND: The multidrug resistance 1 gene (ABCB1) encodes P-glycoprotein (PGP), mainly expressed in the liver and engaged in metabolism of drugs including the immunosuppressant tacrolimus (TAC). ABCB1 single nucleotide polymorphisms (SNP) may significantly alter pharmacokinetics and influence TAC concentrations of kidney transplant recipients (KTR). METHODS: The genotype distribution of ABCB1 1236C>T, 2677G>T/A and 3435C>T was investigated among 96 Austrian KTR who were converted from cyclosporin to TAC...
October 1, 2016: Clinical Laboratory
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