Conversion from twice-daily tacrolimus capsules to once-daily extended-release tacrolimus (LCPT): a phase 2 trial of stable renal transplant recipients.

Abstract:

BACKGROUND:LCP-Tacro is an extended-release formulation of tacrolimus designed for once-daily dosing. Phase 1 studies demonstrated greater bioavailability to twice-daily tacrolimus capsules and no new safety concerns. METHODS:In this phase 2 study, adult stable kidney transplant patients on tacrolimus capsules (Prograf) twice-daily were converted to tacrolimus tablets (LCP-Tacro) once-daily; patients continued on LCP-Tacro once-daily for days 8 to 21; trough levels were to be maintained between 5 and 15 ng/mL; 24-hr pharmacokinetic assessments were done on days 7 (baseline pre-switch), 14, and 21. RESULTS:Forty-seven patients completed LCP-Tacro dosing per protocol. The mean conversion ratio was 0.71. Pharmacokinetic data demonstrated consistent exposure (AUC) at the lower conversion dose. C(max) (P = 0.0001), C(max)/C(min) ratio (P < 0.001), percent fluctuation (P < 0.0001), and swing (P = 0.0004) were significantly lower and T(max) significantly (P < 0.001) longer for LCP-Tacro versus Prograf. AUC24 and C(min) correlation coefficients after 7 and 14 days of therapy were 0.86 or more, demonstrating a robust correlation between LCP-Tacro tacrolimus exposure and trough levels. There were three serious adverse events; none were related to study drug and all were resolved. CONCLUSIONS:Stable kidney transplant patients can be safely converted from Prograf twice-daily to LCP-Tacro. The greater bioavailability of LCP-Tacro allows for once-daily dosing and similar (AUC) exposure at a dose approximately 30% less than the total daily dose of Prograf. LCP-Tacro displays flatter kinetics characterized by significantly lower peak-trough fluctuations.

journal_name

Transplantation

journal_title

Transplantation

authors

Gaber AO,Alloway RR,Bodziak K,Kaplan B,Bunnapradist S

doi

10.1097/TP.0b013e3182962cc1

subject

Has Abstract

pub_date

2013-07-27 00:00:00

pages

191-7

issue

2

eissn

0041-1337

issn

1534-6080

journal_volume

96

pub_type

杂志文章,多中心研究,随机对照试验
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    abstract:BACKGROUND:Serum citrulline is a marker for acute cellular rejection (ACR) after intestinal transplantation; however, its clinical utility has not yet been established. The goal of this study was to determine clearcut serum levels beyond which the diagnosis of acute rejection could be supported or refuted, and predicto...

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    doi:10.1097/01.tp.0000287186.04342.82

    authors: David AI,Selvaggi G,Ruiz P,Gaynor JJ,Tryphonopoulos P,Kleiner GI,Moon JI,Nishida S,Pappas PA,Conanan L,Weppler D,Esquenazi V,Levi DM,Kato T,Tzakis AG

    更新日期:2007-11-15 00:00:00

  • Donor-specific skin transplants activate allodestructive T cells in mice resistant to neonatal H-2 tolerance induction.

    abstract::Mice of the B10 background that are class II I-E nonexpressing demonstrate a relative resistance to neonatal induction of tolerance of class I alloantigens from I-E-expressing B10 strains. The majority of these injected mice delete donor-responsive and "I-E-reactive" (V beta 11+) cells in the immediate postinoculation...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/00007890-199312000-00035

    authors: Nassiri M,Viciana A,Streilein JW,Ruiz P

    更新日期:1993-12-01 00:00:00

  • Pubertal Development in Pediatric Kidney Transplant Patients Receiving Mammalian Target of Rapamycin Inhibitors or Conventional Immunosuppression.

    abstract:BACKGROUND:Data regarding the onset of puberty in children receiving mammalian target of rapamycin (mTOR) inhibitors are limited. METHODS:Kidney transplant patients aged <14 years were analyzed retrospectively to a maximum age of 18 years, with a minimal observation period of 1 year. Immunosuppression comprised (1) st...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/TP.0000000000001037

    authors: Förster J,Ahlenstiel-Grunow T,Zapf A,Mynarek M,Pape L

    更新日期:2016-11-01 00:00:00

  • Studies into the transplantation biology of ultraviolet light-induced tumors.

    abstract::The majority of skin tumors induced in mice by ultraviolet (UV) light are rejected when implanted into normal syngeneic recipients. Subcarcinogenic levels of UV light exposure render the normally resistant mice susceptible to tumor challenge. The immunoregulatory effect of UV light appears to be additive, since the gr...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/00007890-197704000-00008

    authors: Daynes RA,Spellman CW,Woodward JG,Stewart DA

    更新日期:1977-04-01 00:00:00

  • In vivo alloreactive potential of ex vivo-expanded primary T lymphocytes.

    abstract:BACKGROUND:We are presently investigating the therapeutic potential of herpes simplex-thymidine kinase-expressing donor T cells in the setting of a T cell-depleted allogeneic bone marrow transplantation. The generation, expansion, and selection of the gene-modified T cells require a 12-day ex vivo culture period in hig...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/00007890-199805270-00014

    authors: Contassot E,Murphy W,Angonin R,Pavy JJ,Bittencourt MC,Robinet E,Reynolds CW,Cahn JY,Hervé P,Tiberghien P

    更新日期:1998-05-27 00:00:00

  • Quantitative polymerase chain reaction profiling of immunomarkers in rejecting kidney allografts for predicting response to steroid treatment.

    abstract:BACKGROUND:Steroid-resistant acute rejection is a risk factor for inferior renal allograft outcome. METHODS:From 873 kidney transplant recipients (1995-2005), 108 patients with a first rejection episode were selected for study using strict inclusion criteria and clinical endpoint definition. We aimed to predict respon...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/TP.0b013e31825db651

    authors: Rekers NV,Bajema IM,Mallat MJ,Zuidwijk K,Anholts JD,Goemaere N,Haasnoot GW,van Groningen MC,van Kooten C,de Fijter JW,Claas FH,Eikmans M

    更新日期:2012-09-27 00:00:00

  • Sirolimus delays recovery of rat kidney transplants after ischemia-reperfusion injury.

    abstract:BACKGROUND:Sirolimus (SRL) seems to impair renal recovery from ischemic injury in animal models and delayed graft function after clinical renal transplantation. This study determined the impact of SRL on renal recovery after ischemia-reperfusion injury in a rat kidney transplant model. METHODS:Syngeneic kidneys were p...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/01.TP.0000095897.38634.30

    authors: Fuller TF,Freise CE,Serkova N,Niemann CU,Olson JL,Feng S

    更新日期:2003-12-15 00:00:00

  • Cell-mediated cytotoxicity: a predictor of chronic rejection in pediatric HLA haploidentical renal transplants.

    abstract:BACKGROUND:Recipient antidonor cytotoxic T-cell activity has been associated with graft loss and acute rejection in renal allograft recipients. The role of immunologic mechanisms in the development of chronic graft rejection is controversial. We analyzed all living related renal transplants performed at Children's Hosp...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/00007890-199706270-00009

    authors: Alexander SI,Younes SB,Yunis JJ,Zurakowski D,Mirza N,Dubey D,Drew MP,Harmon WE,Yunis EJ

    更新日期:1997-06-27 00:00:00

  • One-year follow-up of an open-label trial of FK506 for primary kidney transplantation. A report of the U.S. Multicenter FK506 Kidney Transplant Group.

    abstract::Patients undergoing primary cadaveric kidney transplantation were followed for 1 year as part of a phase II, multicenter, open-label concentration-ranging trial of FK506 and cyclosporine. One hundred twenty patients were randomly assigned to a cyclosporine-based regimen or one of three FK506-based regimens designed to...

    journal_title:Transplantation

    pub_type: 临床试验,杂志文章,多中心研究,随机对照试验

    doi:10.1097/00007890-199606150-00005

    authors: Vincenti F,Laskow DA,Neylan JF,Mendez R,Matas AJ

    更新日期:1996-06-15 00:00:00

  • The lymphatic drainage of the rat prostate and its status as an immunologically privileged site.

    abstract::Recent suggestions that the rat prostate is an alymphatic, immunologically privileged site stimulated further investigation of its status using a variety of techniques. Fixation of certain organs by vascular perfusion of glutaraldehyde followed by plastic embedding avoids the distortion and stromal reorganization that...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/00007890-197902000-00011

    authors: Neaves WB,Billingham RE

    更新日期:1979-02-01 00:00:00

  • Role of anti-tumor necrosis factor-alpha in ischemia/reperfusion injury in isolated rat liver in a blood-free environment.

    abstract:BACKGROUND:Warm ischemia/reperfusion injury during liver transplantation is the most important cause of primary nonfunction of liver allografts. Tumor-necrosis factor (TNF)-alpha apparently mediates tissue damage by inducing apoptosis and/or necrosis in liver transplants. The aim of the study was to determine, using an...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/00007890-200206270-00004

    authors: Ben-Ari Z,Hochhauser E,Burstein I,Papo O,Kaganovsky E,Krasnov T,Vamichkim A,Vidne BA

    更新日期:2002-06-27 00:00:00

  • Analysis of the interactions of immunosuppressive drugs with cyclosporine in inhibiting DNA proliferation.

    abstract::Though the high immunosuppressive efficacy of cyclosporine has revolutionized clinical transplantation, renal, hepatic, and neural toxicities limit its therapeutic potential. One approach to this problem is to combine CsA therapy with immunosuppressive agents that act synergistically with it, thereby permitting lower ...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/00007890-199002000-00044

    authors: Vathsala A,Chou TC,Kahan BD

    更新日期:1990-02-01 00:00:00

  • Islet graft survival and function: concomitant culture and transplantation with vascular endothelial cells in diabetic rats.

    abstract:BACKGROUND:Human islet transplantation is a great potential therapy for type I diabetes. To investigate islet graft survival and function, we recently showed the improved effects after co-culture and co-transplantation with vascular endothelial cells (ECs) in diabetic rats. METHODS:ECs were isolated, and the viability...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/TP.0b013e3182356ca7

    authors: Pan X,Xue W,Li Y,Feng X,Tian X,Ding C

    更新日期:2011-12-15 00:00:00

  • Correction of decreased guanylate cyclase activity in diabetic rats by pancreatic islet transplantation.

    abstract::We have previously demonstrated that streptozotocin-induced diabetic rats have decreased guanylate cyclase (EC 4.6.1.2) activity in liver and other tissues which was returned to normal by the administration of exogenous insulin. Since successful pancreatic islet transplants have been shown to lower basal hepatic gluco...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:

    authors: Vesely DL,Selawry H,Levey GS

    更新日期:1979-06-01 00:00:00

  • Potential feasibility of early bone marrow cell injection into the spleen for creating functional hepatocytes.

    abstract:BACKGROUND:Bone marrow cells (BMCs) are believed to have the ability to generate functional hepatocytes and have some merits as a therapeutic modality for metabolic liver diseases. However, the appearance of BMC-derived hepatocytes (BMDHs) is low. We hypothesized that early BMC injection would be feasible for creating ...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/TP.0b013e31819e0528

    authors: Misawa R,Soeda J,Ise H,Takahashi M,Kubota K,Mita A,Nakata T,Miyagawa S

    更新日期:2009-04-27 00:00:00

  • The development and specificity of antiidiotypic antibodies in renal transplant recipients receiving single-donor blood transfusions.

    abstract::Multiple pretransplant sera obtained from alloimmunized renal transplant recipients were tested for the presence of antiidiotypic-like antibodies (AB2) that inhibit donor-specific HLA antibodies in the microlymphocytotoxicity assay. Fourteen patients received repetitive single-donor blood transfusions (SDT). In this p...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/00007890-198907000-00013

    authors: Phelan DL,Rodey GE,Anderson CB

    更新日期:1989-07-01 00:00:00

  • Effects of Intraoperative Fluid Balance During Liver Transplantation on Postoperative Acute Kidney Injury: An Observational Cohort Study.

    abstract:BACKGROUND:Liver transplant recipients suffer many postoperative complications. Few studies evaluated the effects of fluid management on these complications. We conducted an observational cohort study to evaluate the association between intraoperative fluid balance and postoperative acute kidney injury (AKI) and other ...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/TP.0000000000002998

    authors: Carrier FM,Chassé M,Sylvestre MP,Girard M,Legendre-Courville L,Massicotte L,Bilodeau M

    更新日期:2020-07-01 00:00:00

  • DSA Are Associated With More Graft Injury, More Fibrosis, and Upregulation of Rejection-associated Transcripts in Subclinical Rejection.

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    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/TP.0000000000003034

    authors: Höfer A,Jonigk D,Hartleben B,Verboom M,Hallensleben M,Hübscher SG,Manns MP,Jaeckel E,Taubert R

    更新日期:2020-03-01 00:00:00

  • Tumor necrosis factor-beta is associated with thymic apoptosis during acute rejection.

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    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/00007890-199810150-00014

    authors: Yamaguchi Y,Okabe K,Miyanari N,Matsumura F,Ichiguchi O,Akizuki E,Matsuda T,Liang J,Ohshiro H,Miyayama Y,Yamada S,Mori K,Ogawa M

    更新日期:1998-10-15 00:00:00

  • Urolithiasis after kidney transplantation in pediatric recipients: a single center report.

    abstract:BACKGROUND:Urolithiasis occurs in approximately 6% of adult kidney transplant (KTx) recipients. Limited data are available on urolithiasis after pediatric KTx. We report the incidence, management of, and risk factors for stone development in children after KTx. METHODS:We reviewed the medical records of 399 children w...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/01.tp.0000139543.56886.de

    authors: Khositseth S,Gillingham KJ,Cook ME,Chavers BM

    更新日期:2004-11-15 00:00:00

  • Effect of blood transfusion on IL-2 production.

    abstract::Spleen cells from B10.A mice transfused with B10.D2 blood suppress the immune responses of normal B10.A to B10.D2 in coculture as early as 2 days posttransfusion. In addition, the ability of B10.A mice to respond in cell-mediated lymphocytotoxicity (CML) is significantly impaired as early as 2 days after B10.D2 transf...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/00007890-198805000-00018

    authors: Wood ML,Gottschalk R,Monaco AP

    更新日期:1988-05-01 00:00:00

  • Endothelial cell preservation using organ storage solutions.

    abstract::The development of organ preservation solutions has been primarily accomplished in whole organ animal models. This study examines the toxicity of commonly used organ preservation solutions on endothelial cells in vitro. Primary human umbilical-vein endothelial cell cultures were incubated at 4 degrees C in solutions o...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/00007890-199205000-00002

    authors: Killinger WA Jr,Dorofi DB,Keagy BA,Johnson G Jr

    更新日期:1992-05-01 00:00:00

  • Circulating markers of endothelial dysfunction interact with proteinuria in predicting mortality in renal transplant recipients.

    abstract:BACKGROUND:Proteinuria is associated with endothelial dysfunction (ED) and increased mortality. We investigated whether urinary protein excretion (UPE) is correlated with markers of ED and whether these markers affect the association of proteinuria with mortality in renal transplant recipients (RTR). METHODS:Six hundr...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/TP.0b013e3181903d25

    authors: van Ree RM,Oterdoom LH,de Vries AP,Homan van der Heide JJ,van Son WJ,Navis G,Gans RO,Bakker SJ

    更新日期:2008-12-27 00:00:00

  • Repeat Kidney Transplantation After Failed First Transplant in Childhood: Past Performance Informs Future Performance.

    abstract:BACKGROUND AND OBJECTIVES:Kidney transplant graft survival is almost uniformly superior for initial transplants compared to repeat transplants. We investigate the association between first second kidney transplant graft survival in patients who underwent initial transplant during their pediatric years whether age at se...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/TP.0000000000000686

    authors: Gupta M,Wood A,Mitra N,Furth SL,Abt PL,Levine MH

    更新日期:2015-08-01 00:00:00

  • Association of polymorphisms of interleukin-8, CXCR1, CXCR2, and selectin with allograft outcomes in kidney transplantation.

    abstract:BACKGROUND:Both chemokines and adhesion molecules mediate allograft rejection by recruiting leukocytes into the allograft. We investigated the association of six single nucleotide polymorphisms (SNPs) located in interleukin (IL)-8, CXCR1, CXCR2, and selectin with kidney allograft outcomes. METHODS:The promoter regions...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/tp.0b013e3181fd0195

    authors: Ro H,Hwang YH,Kim H,Jeong JC,Lee H,Doh YS,Park HC,Oh KH,Park MH,Ha J,Yang J,Ahn C

    更新日期:2011-01-15 00:00:00

  • Red cell antigens and renal transplantation.

    abstract::Donor-specific transfusion was performed with and without cyclosporine between haplomismatched relatives prior to living-donor renal transplantation. Red cell antigen mismatching was not taken as a contraindication to DST. Of 80 patients included in the trial; eleven were ABO-mismatched, 15 were Rh(D)-mismatched, and ...

    journal_title:Transplantation

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1097/00007890-199008000-00019

    authors: Duguid JK,Hillis AN,Bone JM

    更新日期:1990-08-01 00:00:00

  • Combined liver-intestine grafts compared with isolated intestinal transplantation in children: a single-center experience.

    abstract:BACKGROUND:Intestinal transplantation is known to be associated with a high risk of early complications and mortality. METHODS:We analyzed prospective data of 51 primary small bowel transplantations from December 1999 to August 2009 and identified perioperative factors that impact on early mortality (≤6 months after t...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/TP.0b013e318265c508

    authors: Dopazo C,Gupte GL,Sharif K,Perera MT,Hartley J,Muiesan P,Mayer DA,Bromley P,Bennett J,Kelly DA,van Mourik I,McKiernan P,Beath SV,Mirza DF

    更新日期:2012-10-27 00:00:00

  • Factors influencing weight gain after renal transplantation.

    abstract::Weight gain following renal transplantation occurs frequently but has not been investigated quantitatively. A retrospective chart review of 115 adult renal transplant recipients was used to describe patterns of weight gain during the first 5 years after transplantation. Only 23 subjects (21%) were overweight before th...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/00007890-199310000-00008

    authors: Johnson CP,Gallagher-Lepak S,Zhu YR,Porth C,Kelber S,Roza AM,Adams MB

    更新日期:1993-10-01 00:00:00

  • Diarrhea after kidney transplantation: a new look at a frequent symptom.

    abstract::Diarrhea is a frequent but overlooked complication of kidney transplantation. Diarrhea is repeatedly neglected, often considered by patients and clinicians an unavoidable side effect of immunosuppressive regimens. It is, however, associated with a significant impairment in life quality. Severe and chronic posttranspla...

    journal_title:Transplantation

    pub_type: 杂志文章,评审

    doi:10.1097/TP.0000000000000335

    authors: Aulagnon F,Scemla A,DeWolf S,Legendre C,Zuber J

    更新日期:2014-10-27 00:00:00

  • Monocyte-derived dendritic cell precursors facilitate tolerance to heart allografts after total lymphoid irradiation.

    abstract:BACKGROUND:Previous studies have shown that posttransplant total lymphoid irradiation, anti-thymocyte globulin, and an intravenous donor blood cell infusion induce tolerance to ACI heart allografts in Lewis rat hosts. METHODS:In the current study, fresh ACI monocytes and dendritic cell precursors, derived from short-t...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/00007890-199811270-00004

    authors: Hayamizu K,Huie P,Sibley RK,Strober S

    更新日期:1998-11-27 00:00:00