Characterizing the pharmacokinetics and pharmacodynamics of immunosuppressant medicines and patient outcomes in elderly renal transplant patients
TRANSLATIONAL ANDROLOGY AND UROLOGY
Authors: Cossart, Amelia R.; Cottrell, W. Neil; Campbell, Scott B.; Isbel, Nicole M.; Staatz, Christine E.
Abstract
This review examines what is currently known about the pharmacokinetics and pharmacodynamics of commonly prescribed immunosuppressant medicines, tacrolimus, cyclosporine, mycophenolate and prednisolone, in elderly renal transplant recipients, and reported patient outcomes in this cohort. Renal transplantation is increasing rapidly in the elderly, however, currently, long-term patient outcomes are relatively poor compared to younger adults. Some studies have suggested that elderly recipients may have higher dose-adjusted exposure and/or lower clearance of the calcineurin inhibitors tacrolimus and cyclosporine; with one study reporting up to 50% reduction in tacrolimus exposure in the elderly. Elderly transplant recipients do not appear to have higher dosage-adjusted exposure to mycophenolic acid (MPA). The effects of ageing on the pharmacokinetics of prednisolone are unknown. Only one study has examined how aging effects drug target enzymes, reporting no difference in baseline inosine 5'-monophosphate dehydrogenase (IMPDH) activity and MPA-induced IMPDH activity in elderly compared to younger adult renal transplant recipients. In elderly transplant recipients, immunosenescence likely lowers the risk of acute rejection, but increases the risk of drug-related adverse effects. Currently, the three main causes of death in elderly renal transplant recipients are cardiovascular disease, infection and malignancy. One study has showed that renal transplant recipients aged over 65 years are seven times more likely to die with a functioning graft compared with young adults (aged 18-29 years). This suggests that an optimal balance between immunosuppressant medicine efficacy and toxicity is not achieved in elderly recipients, and further studies are needed to foster long-term graft and patient survival. Lower maintenance immunosuppressant targets in elderly recipients may decrease patient susceptibility to drug side effects, however, further studies are required and appropriate targets need to be established.
Liposomal Delivery of Mycophenolic Acid With Quercetin for Improved Breast Cancer Therapy in SD Rats
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
Authors: Patel, Gopal; Thakur, Neeraj Singh; Kushwah, Varun; Patil, Mahesh D.; Nile, Shivraj Hariram; Jain, Sanyog; Banerjee, Uttam Chand; Kai, Guoyin
Abstract
The present study explores the influence of mycophenolic acid (MPA) in combination therapy with quercetin (QC) (impeding MPA metabolic rate) delivered using the liposomal nanoparticles (LNPs). Mycophenolic acid liposome nanoparticles (MPA-LNPs) and quercetin liposome nanoparticles (QC-LNPs) were individually prepared and comprehensively characterized. The size of prepared MPA-LNPs and QC-LNPs were found to be 183 +/- 13 and 157 +/- 09.8, respectively. Thein vitrostudies revealed the higher cellular uptake and cytotoxicity of combined therapy (MPA-LNPs + QC-LNPs) compared to individual ones. Moreover pharmacokinetics studies in female SD-rat shown higherT(1)(/)(2)value (1.94 fold) of combined therapy compared to MPA. Furthermore,in vivoanticancer activity in combination of MPA-LNPs and QC-LNPs was also significantly higher related to other treatments groups. The combination therapy of liposomes revealed the new therapeutic approach for the treatment of breast cancer.