A non-randomized trial of conversion from ciclosporin and tacrolimus to tacrolimus MR4 in stable long-term kidney transplant recipients: Graft function and influences of ABCB1 genotypes
| Autor: | Corinna Steinhauser, Gere Sunder-Plassmann, Markus Riegersperger, Wolfgang C. Winkelmayer, Max Plischke, Anita Jallitsch-Halper, Manuela Födinger, Daniela Dunkler |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Graft Rejection
Male Physiology Biopsy 030230 surgery Graft function Kidney transplant law.invention 0302 clinical medicine Drug Metabolism Randomized controlled trial Animal Cells law Medicine and Health Sciences Renal Transplantation Clinical endpoint Multidisciplinary Stem Cells Middle Aged Tissue Donors Research Design Cyclosporine Medicine Female 030211 gastroenterology & hepatology Cellular Types Immunosuppressive Agents Glomerular Filtration Rate Research Article medicine.drug Medical Ethics medicine.medical_specialty ATP Binding Cassette Transporter Subfamily B Drug Research and Development Genotype Clinical Research Design Science Urology Renal function Surgical and Invasive Medical Procedures chemical and pharmacologic phenomena Research and Analysis Methods Tacrolimus Urinary System Procedures 03 medical and health sciences stomatognathic system medicine Humans Clinical Trials Pharmacokinetics Adverse effect Genetic Association Studies Aged Pharmacology Transplantation Renal Physiology business.industry Biology and Life Sciences Organ Transplantation Cell Biology Ciclosporin Kidney Transplantation Randomized Controlled Trials stomatognathic diseases Adverse Events Clinical Medicine business |
| Zdroj: | PLoS ONE, Vol 14, Iss 7, p e0218709 (2019) PLoS ONE |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0218709 |
| Popis: | In this non-randomized extension study of a randomized controlled trial we converted 87 stable long-term kidney transplant recipients (KTR) from either ciclosporin (CSA, n = 28) or tacrolimus (TAC, n = 59) to TAC modified release (TAC MR4) to study the characteristics of TAC trough levels after conversion with the primary endpoint graft function after 12 months. TAC MR4 consumption was calculated by level-to-dose ([ng/mL]/[mg/d]) and concentration-to-dose ([mg/kg])/d) ratios. Influences of ABCB1 single nucleotide polymorphisms (2677G>T/A, 1236C>T, 3435C>T) on TAC metabolism were studied. Graft function of KTR converted from CSA to TAC MR4 significantly declined over 12 months, and remained unchanged after conversion from TAC to TAC MR4. Conversion from CSA to TAC MR4 resulted in supra therapeutic- and conversion from TAC to TAC MR4 in low trough levels. We could not find associations of ABCB1 genotypes and TAC MR4 trough levels. Adverse events and errors with TAC/TAC MR4 intake were common. In stable long-term KTR conversion from TAC to TAC MR4 is feasible. For conversion from CSA we suggest a rate of 1:40 for a rough estimation of TAC MR4 target doses. Trial registration PEP Study: Ethics committee N° 393/2004, EudraCT 2004-004209-98. PEP-X Study: Ethics committee amendment application N° 154/01/2008. ClinicalTrials.gov NCT03751332. |
| Databáze: | OpenAIRE |
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