Abstract
Immunosuppressive therapy is the cornerstone of successful kidney transplantation. Frequently used immunosuppressives are cyclosporine, tacrolimus, sirolimus and mycophenolic acid. These drugs have narrow therapeutic index and show high pharmacokinetic variability. In order to maintain the balance between efficacy and safety, dosing is based on measured drug concentrations. Proper identification, quantification and understanding the sources of variability in measured concentrations facilitate routine dose adjustment in clinical practice. Classical pharmacokinetic studies have limited use in transplant patients attributable to design with intense sampling in a small, relatively homogenous population, and identification of only single variability factor per study. Population approach is a powerful tool for analysing sparse data, identifying factors that influence drug pharmacokinetics and estimating variability. In this report we reviewed available population pharmacokinetic models for cyclosporine, tacrolimus, sirolimus and mycophenolic acid in adult kidney transplant patients. The major focus was to describe various demographic factors, biochemical parameters, genetic polymorphisms of metabolic enzymes and transporters and drug-drug interactions, which have been identified as an important concern of pharmacokinetic variability in kidney transplant patients.
Keywords: Cyclosporine, tacrolimus, sirolimus, mycophenolic acid, factors of variability, pharmacokinetic, kidney transplant patients, population model.
Current Medicinal Chemistry
Title:Population Pharmacokinetic Approach of Immunosuppressive Therapy in Kidney Transplant Patients
Volume: 23 Issue: 19
Author(s): Bojana Golubovic, Milica Prostran, Branislava Miljkovic, Katarina Vucicevic, Dragana Radivojevic and Iztok Grabnar
Affiliation:
Keywords: Cyclosporine, tacrolimus, sirolimus, mycophenolic acid, factors of variability, pharmacokinetic, kidney transplant patients, population model.
Abstract: Immunosuppressive therapy is the cornerstone of successful kidney transplantation. Frequently used immunosuppressives are cyclosporine, tacrolimus, sirolimus and mycophenolic acid. These drugs have narrow therapeutic index and show high pharmacokinetic variability. In order to maintain the balance between efficacy and safety, dosing is based on measured drug concentrations. Proper identification, quantification and understanding the sources of variability in measured concentrations facilitate routine dose adjustment in clinical practice. Classical pharmacokinetic studies have limited use in transplant patients attributable to design with intense sampling in a small, relatively homogenous population, and identification of only single variability factor per study. Population approach is a powerful tool for analysing sparse data, identifying factors that influence drug pharmacokinetics and estimating variability. In this report we reviewed available population pharmacokinetic models for cyclosporine, tacrolimus, sirolimus and mycophenolic acid in adult kidney transplant patients. The major focus was to describe various demographic factors, biochemical parameters, genetic polymorphisms of metabolic enzymes and transporters and drug-drug interactions, which have been identified as an important concern of pharmacokinetic variability in kidney transplant patients.
Export Options
About this article
Cite this article as:
Golubovic Bojana, Prostran Milica, Miljkovic Branislava, Vucicevic Katarina, Radivojevic Dragana and Grabnar Iztok, Population Pharmacokinetic Approach of Immunosuppressive Therapy in Kidney Transplant Patients, Current Medicinal Chemistry 2016; 23 (19) . https://dx.doi.org/10.2174/0929867323666151221150214
DOI https://dx.doi.org/10.2174/0929867323666151221150214 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
The Development of Medications for Alcohol-Use Disorders Targeting the GABAB Receptor System
Recent Patents on CNS Drug Discovery (Discontinued) Acid-Sensing Ion Channels Structural Aspects, Pathophysiological Importance and Experimental Mutational Data Available Across Various Species to Target Human ASIC1
Current Drug Targets Editorial [Hot Topic: The Pineal Hormone Melatonin in Health and Disease (Guest Editors: Charanjit Kaur)]
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery A Concise Review on Multidimensional Silver Nanoparticle Health Aids and Threats
Current Drug Therapy Pharmacoproteomics Applications for Drug Target Discovery in CNS Disorders
Current Pharmacogenomics and Personalized Medicine Modulation of GABAA Receptors by Natural Products and the Development of Novel Synthetic Ligands for the Benzodiazepine Binding Site
Current Drug Targets Regulatory Triangle of Neurodegeneration, Adult Neurogenesis and MicroRNAs
CNS & Neurological Disorders - Drug Targets Basis for the Application of Analytical Models of the Bloch NMR Flow Equations for Functional Magnetic Resonance Imaging (fMRI): A Review
Recent Patents on Medical Imaging Redox Signaling Pathways Involved in Neuronal Ischemic Preconditioning
Current Neuropharmacology Affective Disorder and Hyperandrogenism
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery In Vivo Imaging of the Metabotropic Glutamate Receptor 1 (mGluR1) with Positron Emission Tomography: Recent Advance and Perspective
Current Medicinal Chemistry GABAA Receptor Specific Pyrazolopyrimidines as Potential Imaging Agents: In Vivo Characteristics of a New 18F-labelled Indiplon Derivative
Current Radiopharmaceuticals Pharmacokinetics and Metabolic Drug Interactions
Current Clinical Pharmacology Current and Future Prospective of a Versatile Moiety: Imidazole
Current Drug Targets Relationship Between the Chemokine Receptor CCR5 and Microglia in Neurological Disorders: Consequences of Targeting CCR5 on Neuroinflammation, Neuronal Death and Regeneration in a Model of Epilepsy
CNS & Neurological Disorders - Drug Targets Editorial [Vigabatrin: An Antiepileptic Drug with Major Benefits but Significant Adverse Effects]
Current Drug Safety Hybrid PET Imaging in Neurologic Disease: PET/MRI Rather than PET/CT
Current Medical Imaging Importance of Aquaporins in the Physiopathology of Brain Edema
Current Pharmaceutical Design A Randomized, Double-Blind, Placebo-Controlled Pilot Trial of Safety and Tolerability of Two Doses of Divalproex Sodium in Outpatients with Probable Alzheimers Disease
Current Alzheimer Research Blood-brain Barrier Drug Discovery for Central Nervous System Infections
Current Drug Targets - Infectious Disorders