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Diarrhoea Tacrolimus Level Rise Mechanism — ESENeph MCQ

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ModerateTransplantationDiarrhoea Tacrolimus Level Rise MechanismESENeph

A kidney transplant recipient on Tacrolimus and Mycophenolate develops norovirus gastroenteritis with profuse diarrhoea. His Tacrolimus trough was 7 ng/mL pre-illness. Two days into the illness, his trough is 14 ng/mL despite unchanged dosing. What is the mechanism?

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Correct answer: D — Diarrhoea increases Tacrolimus absorption (reduced gut transit time allows more proximal absorption where CYP3A4 activity may be overwhelmed) AND reduces Mycophenolate-mediated enterohepatic recycling competition – resulting in supratherapeutic Tacrolimus levels

Diarrhoeal illness in transplant recipients commonly causes Tacrolimus level fluctuations. Mechanisms include: (1) reduced intestinal transit time may paradoxically increase Tacrolimus absorption in some patients (altered site of absorption); (2) intestinal inflammation may increase permeability; (3) reduced food intake alters absorption characteristics; (4) dehydration concentrates the drug. The result is unpredictable but often elevated levels. Conversely, severe diarrhoea may reduce Mycophenolate absorption. Tacrolimus should be temporarily dose-reduced during GI illness with frequent level monitoring.

Reference: KDIGO 2009 – Transplant; Staatz and Tett 2004 – Tacrolimus Pharmacokinetics