Impact of mycophenolate mofetil loading on drug exposure in the early posttransplant period

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.

Reflections on the development and implementation of an early warning system for ecstasy and related drug markets in Australia

Regular and systematic monitoring of drug markets provides the basis for evidence-based policy. In Australia, trends in ecstasy and related drug (ERD) markets have been monitored in selected jurisdictions since 2000 and nationally since 2003, by the Party Drugs Initiative (PDI). The PDI maximises the validity of conclusions by triangulating information from (a) interviews with regular ecstasy users (REU), (b) interviews with key experts and (c) indicator data. There is currently no other system in Australia for monitoring these markets systematically; however, the value of the PDI has been constrained by the quality of available data. Difficulties in recruiting and interviewing appropriate consumers (REU) and key experts have been experienced, but largely overcome. Limitations of available indicator data from both health and law enforcement continue to present challenges and there remains considerable scope for enhancing existing routine data collection systems, to facilitate monitoring of ERD markets. With an expanding market for ecstasy and related drugs in Australia, and in the context of indicator data that continue to be limited in scope and detail, there is a strong argument for the continued collection of annual, comparable data from a sentinel group of REU, such as those recruited for the PDI.