Nauras Shuker - Academia.edu (original) (raw)
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markdownabstractAlthough tacrolimus has been in widespread use since the 1990s, there are still a... more markdownabstractAlthough tacrolimus has been in widespread use since the 1990s, there are still a number of unanswered questions related to its clinical use. For example, the optimal starting dose of tacrolimus and the optimal target concentration in both the early and late phase after transplantation, are unknown. At present, the main challenge to transplant physicians is to improve the long-term outcomes of solid organ transplantation while maintaining the good short-term outcomes that have already been achieved. The aim of this dissertation was to try and answer some of these questions and to find strategies to optimize tacrolimus treatment with the ultimate aim to improve the long-term outcomes of solid organ transplantation.
Clinica Chimica Acta, 2012
Immunosuppressive drugs used in organ transplantation are highly effective in preventing acute re... more Immunosuppressive drugs used in organ transplantation are highly effective in preventing acute rejection. However, the clinical use of these drugs is complicated by the fact that they display highly variable pharmacokinetics and pharmacodynamics between individual patients. The influence of genetic variation on the interindividual variability in immunosuppressive drug disposition, efficacy, and toxicity has been explored in recent years. The polymorphically-expressed ATP-binding cassette (ABC) transporter proteins, in particular ABCB1 and ABCC2, have been investigated extensively because they play an important role in the absorption, distribution and elimination of many immunosuppressive drugs in use today. From these studies it can be concluded that polymorphisms in ABCB1 and ABCC2 have no consistent effect on immunosuppressant pharmacokinetics and toxicity although polymorphisms in ABCB1 appear to be related to the risk of developing calcineurin inhibitorrelated nephrotoxicity. However, the latter needs to be replicated before an individual's ABCB1 genotype can become a useful marker that is applied in clinical practice. Future studies evaluating the influence of ABC transporter gene polymorphisms should explore the relationship with intracellular rather than systemic drug concentrations further in well-designed clinical studies. Until then, single-nucleotide polymorphisms in ABC transporter genes are not suitable to act as biomarkers for solid organ transplantation.
markdownabstractAlthough tacrolimus has been in widespread use since the 1990s, there are still a... more markdownabstractAlthough tacrolimus has been in widespread use since the 1990s, there are still a number of unanswered questions related to its clinical use. For example, the optimal starting dose of tacrolimus and the optimal target concentration in both the early and late phase after transplantation, are unknown. At present, the main challenge to transplant physicians is to improve the long-term outcomes of solid organ transplantation while maintaining the good short-term outcomes that have already been achieved. The aim of this dissertation was to try and answer some of these questions and to find strategies to optimize tacrolimus treatment with the ultimate aim to improve the long-term outcomes of solid organ transplantation.
Clinica Chimica Acta, 2012
Immunosuppressive drugs used in organ transplantation are highly effective in preventing acute re... more Immunosuppressive drugs used in organ transplantation are highly effective in preventing acute rejection. However, the clinical use of these drugs is complicated by the fact that they display highly variable pharmacokinetics and pharmacodynamics between individual patients. The influence of genetic variation on the interindividual variability in immunosuppressive drug disposition, efficacy, and toxicity has been explored in recent years. The polymorphically-expressed ATP-binding cassette (ABC) transporter proteins, in particular ABCB1 and ABCC2, have been investigated extensively because they play an important role in the absorption, distribution and elimination of many immunosuppressive drugs in use today. From these studies it can be concluded that polymorphisms in ABCB1 and ABCC2 have no consistent effect on immunosuppressant pharmacokinetics and toxicity although polymorphisms in ABCB1 appear to be related to the risk of developing calcineurin inhibitorrelated nephrotoxicity. However, the latter needs to be replicated before an individual's ABCB1 genotype can become a useful marker that is applied in clinical practice. Future studies evaluating the influence of ABC transporter gene polymorphisms should explore the relationship with intracellular rather than systemic drug concentrations further in well-designed clinical studies. Until then, single-nucleotide polymorphisms in ABC transporter genes are not suitable to act as biomarkers for solid organ transplantation.