Dosing algorithms for initiation of immunosuppressive drugs in solid organ transplant recipients

Andrews, Louise M.; Riva, Natalia; Winter, Brenda C M de; Hesselink, Dennis A.; Wildt, Saskia N. de; Cransberg, Karlien; Gelder, Teun van

doi:10.1517/17425255.2015.1033397

Cited by 32 publications

(21 citation statements)

References 123 publications

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“…Moreover, these algorithms use a combination of clinical, demographic, and genetic information to determine the Tac dose [106]. So far, a few dosing algorithms suitable to determine the starting dose have been developed [107]. The most extensively researched dosing algorithm was developed by Passey et al [108].…”

Section: Pharmacogenetic Monitoringmentioning

confidence: 99%

Pharmacokinetic considerations related to therapeutic drug monitoring of tacrolimus in kidney transplant patients

Andrews

Winter

et al. 2017

Expert Opinion on Drug Metabolism & Toxicology

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111

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Introduction: Tacrolimus (Tac) is the cornerstone of immunosuppressive therapy after solid organ transplantation and will probably remain so. Excluding belatacept, no new immunosuppressive drugs were registered for the prevention of acute rejection during the last decade. For several immunosuppressive drugs, clinical development halted because they weren't sufficiently effective or more toxic. Areas covered: Current methods of monitoring Tac treatment, focusing on traditional therapeutic drug monitoring (TDM), controversies surrounding TDM, novel matrices, pharmacogenetic and pharmacodynamic monitoring are discussed. Expert opinion: Due to a narrow therapeutic index and large interpatient pharmacokinetic variability, TDM has been implemented for individualization of Tac dose to maintain drug efficacy and minimize the consequences of overexposure. The relationship between predose concentrations and the occurrence of rejection or toxicity is controversial. Acute cellular rejection also occurs when the Tac concentration is within the target range, suggesting that Tac whole blood concentrations don't necessarily correlate with pharmacological effect. Intracellular Tac, the unbound fraction of Tac or pharmacodynamic monitoring could be better biomarkers/tools for adequate Tac exposure -research into this has been promising. Traditional TDM, perhaps following pre-emptive genotyping for Tac-metabolizing enzymes, must suffice for a few years before these strategies can be implemented in clinical practice. ARTICLE HISTORY

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Section: Pharmacogenetic Monitoringmentioning

confidence: 99%

Pharmacokinetic considerations related to therapeutic drug monitoring of tacrolimus in kidney transplant patients

Andrews

Winter

et al. 2017

Expert Opinion on Drug Metabolism & Toxicology

Self Cite

111

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“…[123] In 2011, Passey et al created the first dosing algorithm using a combination of genetic information and clinical factors in adult kidney transplant recipients. The algorithm included CYP3A5 genotype, days post-transplant, age, steroid, and calcium channel blocker use.…”

Section: Dosing Algorithmsmentioning

confidence: 99%

Pharmacogenetic aspects of the use of tacrolimus in renal transplantation: recent developments and ethnic considerations

Tang

Andrews

Gelder

et al. 2016

Expert Opinion on Drug Metabolism & Toxicology

117

114

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Introduction: Tacrolimus (Tac) is effective in preventing acute rejection but has considerable toxicity and inter-individual variability in pharmacokinetics and pharmacodynamics. Part of this is explained by polymorphisms in genes encoding Tac-metabolizing enzymes and transporters. A better understanding of Tac pharmacokinetics and pharmacodynamics may help to minimize different outcomes amongst transplant recipients by personalizing immunosuppression. Areas covered: The pharmacogenetic contribution of Tac metabolism will be examined, with a focus on recent discoveries, new developments and ethnic considerations. Expert opinion: The strongest and most consistent association in pharmacogenetics is between the CYP3A5 genotype and Tac dose requirement, with CYP3A5 expressers having a~40-50% higher dose requirement compared to non-expressers. Two recent randomized-controlled clinical trials using CYP3A5 genotype, however, did not show a decrease in acute rejections nor reduced toxicity. CYP3A4*22, CYP3A4*26, and POR*28 are also associated with Tac dose requirements and may be included to provide the expected improvement of Tac therapy. Studies focusing on the intracellular drug concentrations and on calcineurin inhibitor-induced nephrotoxicity also seem promising. For all studies, however, the ethnic prevalence of genotypes should be taken into account, as this may significantly impact the effect of pre-emptive genotyping.ARTICLE HISTORY

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“…1) is an important drug among the various immunosuppressants used in clinical therapy (Andrews et al, 2015). The mechanism of action of MPA involves inhibition of the conversion of inosine monophosphate by inosine monophosphate dehydrogenase, an essential enzyme required in de novo purine biosynthesis (Franklin and Cook, 1969).…”

Section: Introductionmentioning

confidence: 99%

“…The mechanism of action of MPA involves inhibition of the conversion of inosine monophosphate by inosine monophosphate dehydrogenase, an essential enzyme required in de novo purine biosynthesis (Franklin and Cook, 1969). MPA is widely used in patients who are undergoing solid organ transplantation along with other standard drug regimens such as with tacrolimus, cyclosporine and/or corticosteroids to ensure that graft rejection does not occur (Andrews et al, 2015). MPA in the form of its prodrug is administered to patients undergoing kidney, heart, liver, lung, bowel, pancreas and bone marrow transplantation (Villarroel et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

A comprehensive review of the published assays for the quantitation of the immunosuppressant drug mycophenolic acid and its glucuronidated metabolites in biological fluids

Syed

Srinivas²

2016

Biomedical Chromatography

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Therapeutic use of mycophenolic acid (MPA) is steadily on the rise in combination with other immunosuppressant drugs in transplantation patients. The biotransformation of MPA resulted in the formation of glucuronide metabolites, MPAG and AcMPAG. There are a plethora of assays validated for the analysis of MPA alone or with MPAG/AcMPAG in various biological specimens including plasma/serum, urine, ultrafiltrate, saliva, PBMC, dried blood spots, tissue extract, tumor biopsies and vitreous humor. Based on the need for experimental work, a proper choice of the assay and internal standard may be made using the choices in the literature. While the chemical methods involving high-performance liquid chromatography (HPLC) or LC coupled with triple quadrupole mass spectrometry (LC-MS/MS) are popular, enzymatic assays, in spite of their higher bias, have been used for the routine drug monitoring of MPA. The objectives of the present review are: (a) to provide a focused systematic compilation of the HPLC or LC-MS/MS methods for MPA, MPAG and/or AcMPAG published in the last decade (2005 to current) to enable visual comparison of the methods; (b) to compare and contrast a few enzymatic assays with those of the chemical methods; and (c) to discuss relevant issues/limitations and perspectives on select assays under various subheadings.

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Dosing algorithms for initiation of immunosuppressive drugs in solid organ transplant recipients

Cited by 32 publications

References 123 publications

Pharmacokinetic considerations related to therapeutic drug monitoring of tacrolimus in kidney transplant patients

Pharmacokinetic considerations related to therapeutic drug monitoring of tacrolimus in kidney transplant patients

Pharmacogenetic aspects of the use of tacrolimus in renal transplantation: recent developments and ethnic considerations

A comprehensive review of the published assays for the quantitation of the immunosuppressant drug mycophenolic acid and its glucuronidated metabolites in biological fluids

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