Acute pancreatitis due to tacrolimus in kidney transplant and review of the literature.

WHAT IS KNOWN AND OBJECTIVE: The purpose of this case report is to increase the awareness of tacrolimus-induced acute pancreatitis in renal transplantation patients. CASE SUMMARY: We present a case of tacrolimus-induced acute pancreatitis with positive rechallenge. The 24-year-old male patient underwent kidney transplant and received immunosuppressive therapy with tacrolimus. On day 10 post-transplant, he presented with abdominal pain. A laboratory analysis showed elevated serum amylase and serum lipase levels. An abdominal computed tomography scan showed large-volume ascites and pelvic cavity effusion. These findings led to a diagnosis of acute pancreatitis. After tacrolimus was temporarily stopped and altered with cyclosporine, his symptoms decreased and he was restarted with tacrolimus. On day 61, laboratory tests again revealed significant elevations of serum amylase and serum lipase. A computed tomography scan of the abdomen showed increased pancreatic tail fluid collections. We excluded other possible causes and concluded that tacrolimus was the definite inducer of pancreatitis. The patient was switched from tacrolimus to cyclosporine again. Serum amylase and serum lipase were gradually decreased to normal, and he was discharged home with no relapse. WHAT IS NEW AND CONCLUSION: With the consideration of the wide use of tacrolimus, it is important that healthcare providers are aware of tacrolimus-induced acute pancreatitis. Future studies are needed to confirm and quantify the risk of tacrolimus-induced acute pancreatitis.

Influence of Genetic Polymorphisms on Mycophenolic Acid Pharmacokinetics and Patient Outcomes in Renal Transplantation.

BACKGROUND: Mycophenolic Acid (MPA) is an immunosuppressive drug widely used in the treatment of organ transplantation and autoimmune diseases. Pharmacokinetics and pharmacodynamics of MPA varies between individuals, the potential reasons being the genetic polymorphisms in key enzymes, drug transporters and target proteins of MPA. OBJECTIVE: We try to provide pharmacogenomics information for drug selection and dose adjustment, aiming to improve drug efficacy and reduce side effects in clinical application of MPA. METHODS: In this review, we summarize the literatures in Pubmed that reported MPA-related Single Nucleotide Polymorphisms (SNPs) of renal transplant patients in recent 15 years. RESULTS: Genetic polymorphisms involving uridine diphosphate glucuronosyltransferase enzymes, organic anion transport polypeptides, multidrug resistance-associated protein 2, inosine monophosphate dehydrogenase and immune- response mediators may be associated with the metabolism, efficacy and toxicity of MPA, thus resulting in different MPA exposure and patient outcomes in renal transplantation. CONCLUSION: Several SNPs show significant association with MPA pharmacokinetics and pharmacodynamics, but conflicting results are reported, and no studies on MPA genetic polymorphisms have been translated into clinical practice. More prospective studies are needed to clear the role of genetic polymorphisms on MPA in renal transplantation patients.

Effects of CYP3A5 polymorphisms on tacrolimus pharmacokinetics in pediatric kidney transplantation: a systematic review and meta-analysis of observational studies.

BACKGROUND: CYP3A5 genetic polymorphisms have been reported to be strongly associated with the tacrolimus pharmacokinetics in adult kidney transplantation. However, there is no published meta-analysis in the influence of CYP3A5 variants on the requirements of the tacrolimus dose in pediatric renal-transplant recipients (RTRs). We wished to determine the effects of CYP3A5 polymorphisms on tacrolimus pharmacokinetics in pediatric RTRs. METHODS: A literature search was conducted to include relevant articles by searching PubMed, EMBASE and the Cochrane Central Register of Controlled Trials. Pharmacokinetic-associated parameters such as dose administration, as well as concentrations and dose-adjusted concentrations of tacrolimus were extracted and the meta-analysis undertaken. RESULTS: The meta-analysis involved four studies and one study series involving 268 pediatric RTRs. A significant difference was observed in the mean trough concentration/dose of tacrolimus between recipients carrying CYP3A5* 3/*3 variants (referred to as "non-expressers") and those carrying CYP3A5*1 (referred to as "expressers") [standard mean difference (SMD)=-1.09, 95% confidence interval (CI): -1.92 to -0.25, P=0.011]. Moreover, significance was observed in the mean daily dose of tacrolimus between non-expressers and expressers in pediatric RTRs (SMD=0.44, 95% CI: 0.20 to 0.68, P<0.001). CONCLUSION: Our meta-analysis identified a positive correlation between CYP3A5 genotypes and tacrolimus pharmacokinetics in pediatric RTRs.

FK506-binding protein 12 ligands: a patent review.

INTRODUCTION: FK506-binding protein 12 (FKBP12) is an endogenous protein with peptidyl-prolyl isomerase (PPIase) activity. Natural compounds FK506, rapamycin and ascomycin, are FKBP12 ligands used for treating organ transplant rejection and other diseases. Small ligands that also interact with FKBP12 are designed and synthetized based on the natural ligands. This suggests that targeting FKBP12 has potential in the treatment of multiple diseases. AREAS COVERED: This article describes the features of FKBP12 and the therapeutic actions of agents targeting FKBP12 reported in the published articles and patents. EXPERT OPINION: The multiple functions of FKBP12 cause side effects during therapy with FKBP12 ligands. The interaction between FKBP12 and other receptors should be explored to guide their use as drugs in the clinical setting. In addition, the neuroprotective mechanism of small-molecule FKBP12 ligands needs further study in order to develop them as novel drugs for treating neurological disorders.