Delayed trough level measurement with the use of prolonged-release tacrolimus

Abstract

Summary Trough concentrations of prolonged‐release tacrolimus are usually measured at 24 h after taking the drug in the morning. It is impractical to measure these trough concentrations in patients who visit the outpatient clinic in the afternoon. Trough concentrations obtained in the afternoon may also be suitable for estimating the 24‐h exposure. We therefore aimed to assess the usefulness of tacrolimus concentrations measured at 32 h postdose for therapeutic drug monitoring in renal transplant patients who take prolonged‐release tacrolimus. We measured tacrolimus pharmacokinetics in 26 patients using prolonged‐release tacrolimus. Eleven blood samples were taken during a period of 32 h after ingestion by use of a validated dried blood spot method. Tacrolimus concentrations were measured with HPLC‐tandem mass spectrometry. The mean concentrations at 24 and 32 h postdose were 8.3 μg/l (7.5–9.1) and 6.7 μg/l (6.1–7.4), respectively (P < 0.0001). The Spearman correlation coefficients between these concentrations and 24‐h exposure were 0.83 and 0.82, respectively (both P < 0.01). In conclusion, delayed trough level measurement provides lower values and therefore requires adjustment of the target range. However, levels measured until 32 h after ingestion remain strongly correlated with 24‐h exposure. This warrants the use of delayed trough level measurement to improve patient convenience.

Clinical Pharmacokinetics of Once-Daily Tacrolimus in Solid-Organ Transplant Patients

“…There was not always a strong indication of association (with sometimes only 60 % of variability explained). In one study involving 26 stable renal transplant recipients, tacrolimus trough measurements taken from 26 to 32 h after Advagraf Ò dosing were found to have a correlation with tacrolimus AUC 0-24 similar to that of a measurement taken 24 h after dosing [58]. The authors suggested that in patients in whom it was impractical to get a 24-h trough measurement because of an afternoon outpatient clinic appointment, a later 'delayed' trough value may still be useful, although the trough target range would need to be lowered accordingly.…”

Evaluation of Flexible Tacrolimus Drug Concentration Monitoring Approach in Patients Receiving Extended‐Release Once‐Daily Tacrolimus Tablets

“…An article by van Boekel et al (2015) assessed the correlation between blood concentrations of ER-Tac taken at C 32 and AUC 0-24 . 22 The study was conducted under the premise that exposure assessed at C 32 would be more convenient to the patient by allowing for afternoon clinic appointments. That study found good correlations between tacrolimus concentrations (drawn 24, 26, 28, 30, and 32 hours postdose) and AUC 0-24 (P < .01 for each point).…”

“…That study found good correlations between tacrolimus concentrations (drawn 24, 26, 28, 30, and 32 hours postdose) and AUC 0-24 (P < .01 for each point). 22 The relevance of alternative monitoring strategies is highlighted in a recently published study by Valizadeh et al (2016). 23 They found that among 16 potential stressors following a kidney transplant, patients rated "travelling for check-up" as the fourth highest stressor, right after "fear of graft rejection," "financial pressure," and "uncertainly about future health."…”

“…Given this, it is not surprising that alternative monitoring strategies have been published for extended‐release tacrolimus formulations. An article by van Boekel et al (2015) assessed the correlation between blood concentrations of ER‐Tac taken at C 32 and AUC 0–24 . The study was conducted under the premise that exposure assessed at C 32 would be more convenient to the patient by allowing for afternoon clinic appointments.…”

A preliminary study searching for the right dose of tacrolimus in very young (≤4 years) renal transplant patients

“…For long‐term follow‐up novel sampling strategies, such as with dried blood spot (DBS) finger pricks (require only one drop of blood applied on filter paper) could be of great value to address the challenges with AUC determination and LSS encountered in children. A tacrolimus DBS assay is currently used for clinical practice in adults in our institute …”