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Published on: November 8, 2015
Impact of mycophenolate mofetil loading on drug exposure in the early posttransplant period
B A Kiberd1, J J Puthenparumpil, A Fraser
1Department of Medicine, Dalhousie University, 5082 AC Dickson, Queen Elizabeth II HSC-VG site, Halifax, Nova Scotia B3H 2Y9, Canada.
Unlabelled:
Achieving adequate therapeutic levels of immunosuppressive medications is important in rejection prevention. This study examined exposure to mycophenolic acid (MPA) in kidney transplant patients within the first 5 days posttransplantation.
Methods:
This single-center, nonrandomized study of first solitary kidney allograft recipients receiving cyclosporine (n = 116) or tacrolimus (n = 50) included patients who received either 1 g or 1.5 g of mycophenolate mofetil twice daily starting postoperatively. Exposure to MPA was measured at days 3 and 5 posttransplant using published limited sampling time equations.
Results:
There were no significant differences in exposure in the cyclosporine-treated patients receiving 3-g (n = 22) compared to 2-g (n = 94) daily doses (AUC([0-12]) 33.8 +/- 10.0 mg*h/L versus 30.1 +/- 9.7 mg*h/L, P = .20, respectively). About half the patients in both groups had AUC([0-12]) <30 mg*h/L on days 3 and 5 posttransplant. On the other hand, there was significantly greater exposure on day 3 in the tacrolimus-treated patients receiving 3 g (n = 21) compared to 2 g (n = 29) daily (AUC([0-12]) 43.1 +/- 9.0 mg*h/L versus 36.8 +/- 11.1 mg*h/L, P = .016, respectively). On day 3 one (4.8%) patient receiving 3 g had an AUC([0-12]) of <30 mg*h/L; whereas, eight (27.5%) receiving 2 g were below this level (P = .068). The AUC([0-12]) levels were not different on day 5.
Conclusions:
Loading with higher doses of mycophenolate mofetil results in greater exposure and a trend toward more patients in the therapeutic window within the first week for tacrolimus- but not for cyclosporine-treated patients.
Insights
Higher doses of mycophenolate mofetil improve drug exposure in kidney transplant patients, particularly those on tacrolimus. This enhances the likelihood of achieving therapeutic levels for better rejection prevention.
Area of Science:
- Pharmacology
- Transplantation Medicine
- Nephrology
Background:
- Achieving adequate therapeutic levels of immunosuppressive medications is crucial for preventing rejection in kidney transplant recipients.
- Mycophenolic acid (MPA) is a key immunosuppressant, and its exposure needs careful monitoring post-transplantation.
Purpose of the Study:
- To examine the exposure to mycophenolic acid (MPA) in kidney transplant patients within the first 5 days posttransplantation.
- To compare the impact of different mycophenolate mofetil (MMF) doses on MPA exposure in patients receiving either cyclosporine or tacrolimus.
Main Methods:
- Single-center, nonrandomized study involving first solitary kidney allograft recipients.
- Patients received either 1 g or 1.5 g of mycophenolate mofetil (MMF) twice daily, starting postoperatively.
- MPA exposure was measured at days 3 and 5 posttransplant using limited sampling time equations.
Main Results:
- No significant difference in MPA exposure was observed between 2-g and 3-g daily MMF doses in cyclosporine-treated patients.
- Approximately half of the patients in both cyclosporine groups had MPA exposure below 30 mg*h/L.
- Tacrolimus-treated patients receiving a 3-g daily MMF dose showed significantly greater MPA exposure on day 3 compared to those on a 2-g dose.
Conclusions:
- Higher doses of MMF lead to increased MPA exposure.
- Higher MMF doses show a trend towards more patients achieving therapeutic MPA levels within the first week in tacrolimus-treated patients, but not in cyclosporine-treated patients.
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