Aims: Imatinib is considered the standard first‐line treatment in newly diagnosed patients with chronic‐phase myeloid leukaemia (CML). Several imatinib population pharmacokinetic (popPK) models have been developed. However, their predictive performance has not been well established when extrapolated to different populations. Therefore, this study aimed to perform an external evaluation of available imatinib popPK models developed mainly in adult patients, and to evaluate the improvement in individual model‐based predictions through Bayesian forecasting computed by each model at different treatment occasions.Methods: A literature review was conducted through PubMed and Scopus to identify popPK models. Therapeutic drug monitoring data collected in adult CML patients treated with imatinib was used for external evaluation, including prediction‐ and simulated‐based diagnostics together with Bayesian forecasting analysis.Results: Fourteen imatinib popPK studies were included for model‐performance evaluation. A total of 99 imatinib samples were collected from 48 adult CML patients undergoing imatinib treatment with a minimum of one plasma concentration measured at steady‐state between January 2016 and December 2020. The model proposed by Petain et al showed the best performance concerning prediction‐based diagnostics in the studied population. Bayesian forecasting demonstrated a significant improvement in predictive performance at the second visit. Inter‐occasion variability contributed to reducing bias and improving individual model‐based predictions.Conclusions: Imatinib popPK studies developed in Caucasian subjects including α1‐acid glycoprotein showed the best model performance in terms of overall bias and precision. Moreover, two imatinib samples from different visits appear sufficient to reach an adequate model‐based individual prediction performance trough Bayesian forecasting.

Invasive aspergillosis (IA) is an opportunistic infection affecting immunocompromised patients. Current clinical guidelines support the use of voriconazole for the treatment of IA, although this treatment is not free of interactions in this group of patients who are often treated with polytherapy; in these cases, isavuconazole may be a safe alternative with a lower risk of interactions. The oral route is commonly preferred to the parenteral route, but in patients who do not have access to the enteral route, the use of isavuconazole is limited to the parenteral route only, since the technical information sheet does not recommend the handling of tablets for enteral administration, stating that the capsules should not be chewed, crushed, dissolved or opened. This paper presents the case of a patient with diffuse large B-cell lymphoma with confirmed AI on treatment with isavuconazole by enteral tube. It is detailed here that isavuconazole concentrations are maintained when administered by enteral tube, as measured by therapeutic pharmacokinetic monitoring of its plasma concentrations. Administering isavuconazole by enteral tube was found to be a safe practice with monitoring of its plasma concentrations.

Background: Mitotane is the cornerstone adjuvant and palliative treatment for adrenocortical carcinoma (ACC), requiring strict therapeutic drug monitoring (TDM) due to its narrow therapeutic window and high inter- and intra-individual pharmacokinetic variability. As a highly lipophilic compound, mitotane may be influenced by plasma lipid levels; however, current TDM protocols do not systematically incorporate lipid profile assessment. We report a case illustrating the clinical impact of hypertriglyceridemia on measured mitotane plasma concentrations. Methods: We retrospectively analyzed clinical, biochemical, and pharmacokinetic data from a patient with metastatic ACC treated with oral mitotane. Plasma mitotane concentrations were correlated with triglyceride and cholesterol levels using Spearman’s rank correlation analysis. Results: A 50-year-old male with metastatic ACC experienced abrupt fluctuations in mitotane plasma concentrations despite stable dosing. Supratherapeutic mitotane levels coincided with episodes of marked hypertriglyceridemia. A significant positive correlation was observed between triglyceride levels and plasma mitotane concentrations (ρ = 0.802, p < 0.001), as well as with total cholesterol (ρ = 0.658, p < 0.001). Conclusions: This case highlights a clinically relevant interaction between triglyceride levels and measured mitotane concentrations. Incorporating routine lipid profile assessment into mitotane TDM protocols may improve interpretation of plasma levels and therapeutic decision-making. Prospective studies are warranted to validate these findings and refine monitoring strategies.

Background: Invasive aspergillosis (IA) is an opportunistic infection that affects immunocompromised patients. While voriconazole is commonly used for IA treatment, it presents the risk of drug interactions, particularly in patients on polytherapy. Isavuconazole may serve as a safer alternative with fewer interactions. However, the use of isavuconazole is typically limited to the parenteral route for patients without access to the enteral route, due to recommendations against tablet handling for enteral administration. The objective of this study was to evaluate the suitability of isavuconazole administration via an enteral tube, by therapeutic drug monitoring of isavuconazole plasma concentrations. Methods: This case study examines a patient with diffuse large B-cell lymphoma who was diagnosed with IA and treated with isavuconazole via an enteral tube. Therapeutic pharmacokinetic monitoring of isavuconazole plasma concentrations was performed to assess the feasibility and safety of enteral administration. Results: The results show that isavuconazole concentrations were maintained within the therapeutic range when administered via an enteral tube. No significant deviations in plasma concentration were noted during the monitoring period. Conclusions: Administering isavuconazole through an enteral tube is a safe and viable alternative for patients that are unable to receive the drug via the oral route. Therapeutic monitoring of plasma concentrations is recommended to ensure proper dosing and efficacy.

Adrenocortical carcinoma (ACC) is a rare and aggressive cancer of the adrenal cortex. The first-line treatment for patients with advanced/metastatic disease is mitotane, either as monotherapy or in combination with chemotherapy. Mitotane is an adrenolytic drug with low aqueous solubility and a high volume of distribution, with adipose tissue being its primary site of distribution. This leads to high inter- and intra-individual variability in bioavailability, highlighting the need for monitoring plasma concentrations. We present the case of a 50-year-old man with metastatic ACC. Oral mitotane treatment was initiated, and abrupt variations in plasma concentrations were observed despite consistent dosing. Subsequently, supratherapeutic concentrations were found to coincide with elevated triglyceride levels, prompting a complete lipid profile to be requested after each monitoring session. This case underscores the importance of monitoring dyslipidemia in patients undergoing mitotane therapy.