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Updated: Aug 6, 2026
08:38
Quantification of the Immunosuppressant Tacrolimus on Dried Blood Spots Using LC-MS/MS
Published on: November 8, 2015
Low Tacrolimus C0/Dose Ratio is Associated with Higher Cmax and AUC Despite Similar Pre-dose Concentrations
Amar D Levens1,2, Teun van Gelder1,2, Armin Gelinck3,2
1Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, 2333 ZA, Leiden, The Netherlands.
Clinical Pharmacokinetics
|July 22, 2026
Summary
The tacrolimus concentration-to-dose ratio (C0/dose) better reflects overall drug exposure than pre-dose concentration (C0) alone after kidney transplantation. This ratio helps identify patients with higher tacrolimus exposure, guiding personalized therapeutic drug monitoring.
Area of Science:
- Pharmacology
- Nephrology
- Transplantation Medicine
Background:
- Tacrolimus therapeutic drug monitoring (TDM) in kidney transplant recipients typically relies on pre-dose concentration (C0).
- The tacrolimus concentration-to-dose ratio (C0/dose) is increasingly recognized for its association with clinical outcomes.
- C0 alone may not fully capture variations in peak (Cmax) and total (AUC0-24h) tacrolimus exposure.
Purpose of the Study:
- To evaluate the utility of the tacrolimus C0/dose ratio in assessing overall drug exposure.
- To compare tacrolimus Cmax and AUC0-24h across different C0/dose categories.
- To determine if C0/dose can identify patients with disproportionate tacrolimus exposure.
Main Methods:
- Analysis of 635 tacrolimus pharmacokinetic profiles from 534 kidney transplant recipients.
- Classification of patients into fast, intermediate, and slow C0/dose categories.
- Comparison of Cmax and AUC0-24h using linear mixed-effects models, with sensitivity analyses on a larger cohort.
Main Results:
- The fast C0/dose category showed significantly higher tacrolimus Cmax and AUC0-24h compared to the slow category, despite similar C0 levels.
- Differences in exposure were more pronounced with extended-release tacrolimus formulations.
- These findings remained consistent across different analyses and tacrolimus formulations.
Conclusions:
- Tacrolimus C0 is an incomplete measure of drug exposure and may miss peak-related toxicity.
- The C0/dose ratio is a valuable tool for identifying patients with disproportionate tacrolimus exposure.
- Individualized TDM strategies beyond C0 monitoring are recommended for specific patient groups.
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