The aDOPT Trial (Dose Optimisation Prior to Transplant): In kidney transplantation, can pre-transplant blood levels of mycophenolic acid (MPA) help to optimise individual patient's post-transplant mycophenolate mofetil (MMF) dose to improve outcomes?

This trial involves administering a drug (MMF) at an unapproved time, for the purposes of pharmacokinetic analysis. We plan to compare pre-renal transplant total and free MPA pharmacokinetics with post-renal transplant pharmacokinetics, on the same dose. This drug is standard care post-renal transplant. Post-transplant intervention is purely the pharmacokinetic assessment. We aim to test proof-of-concept that a pre-transplant free MPA concentration assessment (TDM) improves early post-transplant MPA exposure, in a prospective pharmacokinetic trial. All patients will have standard dose MMF pre- and post-renal transplant. We will model a virtual data set of the exposure to MPA which would have occurred if we had adjusted the dose based on the pre-transplant PK assessment. We will additionally model peri-transplant change in total and free MPA pharmacokinetics, and over the first 3 months post transplant. This will include assessment of the between-occasion variability of free MPA pharmacokinetics, to assess the degree to which time-dependant clearance in total MPA relates to plasma protein binding changes in a tacrolimus co-treatment population. Oral mycophenolate mofetil will be administered for 4 days, at a within 1 month prior to planned living donor renal transplant, with pharmacokinetic assessment on day 4. For planned cadaveric donor renal transplant, there is no restriction on dosing and PK assessment timing (and transplant date is unknown). Following renal transplantation, mycophenolate mofetil will be administered as part of standard care, and we will perform repeat pharmacokinetic assessment on around day 4, week 1-2, and week 6-12. The pre-transplant dose will be whatever the treating clinician plans to administer post-transplant (there is some practice variation between centres and depending on individual patient risk). For adults this will be either MMF 1g oral twice daily or 1.5g oral twice daily. For children this will be between 300mg/m2/dose oral twice daily to 600mg/m2/dose oral twice daily. Adherence will be monitored by medication return, and patients will fill out a dosing sheet to document time of each administration. The day 4 MMF dose will be observed.