Dosing tacrolimus based on CYP3A5 genotype: will it improve clinical outcome?
Tacrolimus, widely used to prevent acute rejection following solid-organ transplantation, has become the cornerstone of immunosuppressive therapy after kidney transplantation. More than 70% of all renal transplant recipients receive this remarkably effective agent.(1) But tacrolimus is also highly toxic, and there is great between-patient variability in its pharmacokinetics. This, combined with a low therapeutic index, mandates routine therapeutic drug monitoring in clinical practice.(2) Typically, predose concentrations are monitored and the dose is adjusted to aim for target values that depend on immunological risk, comedication, and time since transplantation.(2).
van Gelder
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Department of Hospital Pharmacy, Erasmus Medical Center, Rotterdam, The Netherlands. t.vangelder@erasmusmc.nl
Hesselink
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D051544:Cytochrome P-450 CYP3A / Q000235:genetics*; D004305:Dose-Response Relationship, Drug; D016903:Drug Monitoring / Q000379:methods; D005838:Genotype; D006084:Graft Rejection / Q000235:genetics / Q000517:prevention & control; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D016030:Kidney Transplantation; D012307:Risk Factors; D016559:Tacrolimus / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome
D007166:Immunosuppressive Agents; C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A; D016559:Tacrolimus