Calcium did not alter tacrolimus or mycophenolate exposure in transplant recipients

Design

Within-patient crossover pharmacokinetic study with volumetric microsampling

Population

25 stable kidney transplant recipients on mycophenolate, tacrolimus and prednisolone

Primary outcome

AUC0–12 and Cmax ratios with versus without calcium/vitamin D

Effect

MPA AUC ratio 0.94 (90% CI 0.83–1.07); tacrolimus AUC ratio 1.00 (0.92–1.09); MPA Cmax 0.79 (0.65–0.97)

A crossover pharmacokinetic study in the British Journal of Clinical Pharmacology, published on 31 October, measured mycophenolic acid and tacrolimus over 12 hours in 25 stable kidney transplant recipients, once with and once without a calcium and vitamin D supplement taken at the same time. Capillary microsampling made the 12-hour profiles practical.

Total exposure (AUC) was unchanged for both drugs: the ratio was 0.94 for mycophenolic acid and 1.00 for tacrolimus, within bioequivalence limits. Peak mycophenolic acid concentration was about 21% lower with calcium, but peak levels matter less than total exposure for this drug.

Interaction databases currently advise separating calcium and mycophenolate by two to three hours. That adds another timing rule to an already complex regimen and may worsen adherence. This study suggests the rule is not needed.

The study was small and in stable patients, so it does not cover the early post-transplant period or other calcium salts and doses.

• Consider allowing calcium with vitamin D to be taken alongside mycophenolate and tacrolimus in stable transplant recipients.
• Simplify dosing schedules where separation rules add burden without benefit.
• Continue routine tacrolimus trough monitoring as usual.
• Keep separating calcium from drugs where chelation is established, such as levothyroxine and quinolones.

Why it matters

Removing an unnecessary timing rule makes a heavy post-transplant regimen easier to follow.

Don't overread it

With 25 stable patients, this does not cover the early post-transplant period or other calcium preparations.

The statistics, in plain English

Bioequivalence is shown when the 90% confidence interval of the exposure ratio lies within 0.80 to 1.25. For tacrolimus AUC it was 0.92 to 1.09, and for mycophenolic acid 0.83 to 1.07, both inside. The peak-level ratio for mycophenolic acid (0.79, 0.65 to 0.97) fell below that range.

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