‘Therapeutic drug monitoring of posaconazole delayed release tablet while managing COVID‐19 associated mucormycosis in a real‐life setting’

ABSTRACT We continuously determined posaconazole plasma concentrations (PPCs) in 61 patients with hematological malignancies receiving posaconazole (PCZ) delayed-release tablets (DRT; 48 patients; median duration of intake, 92 days) and PCZ oral solution (OS; 13 patients; median duration of intake, 124 days). PCZ DRT and OS antifungal prophylaxis was efficient and well tolerated. Thirty-four of 48 patients (71%) receiving DRT always had PPCs of >0.7 mg/liter, while 14 of 48 patients (29%) had at least one PPC of ≤0.7 mg/liter. In patients receiving OS, 4 of 13 patients (31%) always had PPCs of >0.7 mg/liter, 6 of 13 patients (46%) had at least one PPC of ≤0.7 mg/liter, and 3 (23%) patients never reached a PPC of 0.7 mg/liter. In patients with at least one determined PPC, the mean proportion of all PPCs of >0.7 mg/liter was 91% for PCZ DRT, whereas it was 52% for PCZ OS ( P = 0.001). In the per sample analysis, PPCs were significantly more likely to be >0.7 mg/liter in patients receiving DRT than in patients receiving OS (PPCs were >0.7 mg/liter in 91.4% [297/325] of patients receiving DRT versus 70.3% [85/121] of patients receiving OS; P < 0.001). Patients receiving PCZ DRT had higher proportions of PPCs of >0.7 mg/liter than patients receiving OS both in the per patient and in the per sample analyses. Two patients (3%) had side effects during PCZ prophylaxis, and one (2%) had fungal breakthrough infection. Therapeutic drug monitoring enables detection of extended periods of PPCs of ≤0.7 mg/liter (e.g., due to nonadherence or graft-versus-host disease), which may also be associated with the loss of protective intracellular PCZ concentrations, regardless of the PCZ formulation.

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Concomitant intake of abiraterone and food to increase pharmacokinetic exposure: Real-life data from a therapeutic drug monitoring program.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.3117 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. 3117-3117 ◽

Cited By ~ 1

Author(s):

Stefanie L. Groenland ◽

Andre M. Bergman ◽

Alwin Huitema ◽

Neeltje Steeghs

Keyword(s):

Therapeutic Drug Monitoring ◽

Drug Monitoring ◽

Monitoring Program ◽

Real Life ◽

Progression Free Survival ◽

Abiraterone Acetate ◽

Fixed Dose ◽

Therapeutic Drug ◽

Castration Resistant Prostate Cancer ◽

Regular Treatment

3117 Background: Abiraterone acetate is registered for the treatment of metastatic castration resistant prostate cancer. Pharmacokinetic (PK) exposure has been linked to efficacy, since patients with Cmin ≥ 8.4 ng/mL have a significantly longer progression free survival compared to patients with a Cmin below this threshold (7.4 vs. 12.2 months, p = 0.044) (Carton, 2017). At the recommended fixed dose of 1000 mg QD administered in a modified fasting state, 35% of patients do not reach this efficacy threshold (Carton, 2017), providing a strong rationale for therapeutic drug monitoring (TDM). Since a clinically relevant food effect has been established, concomitant intake of abiraterone and food could offer a cost-neutral solution in case of low exposure (Chi, 2015). This study aims to evaluate whether PK-guided abiraterone dosing is feasible and results in an increased proportion of patients with concentrations above the target. Methods: Patients starting regular treatment with abiraterone were included. PK sampling occurred 4, 8 and 12 weeks after start of treatment, and every 12 weeks thereafter. Abiraterone concentrations were measured and Cmin was calculated. In case of Cmin < 8.4 ng/mL and acceptable toxicity, a PK-guided intervention was advised. As a first step, concomitant intake of abiraterone and a light meal or a snack was advised. Results: In total, 35 patients were included, of which 18 patients (51%) had at least one Cmin < 8.4 ng/mL. These patients were advised to take abiraterone concomitantly with food, after which Cmin increased significantly from 5.6 (47%) ng/mL [mean (CV%)] to 40.6 (110%) ng/mL (p = 0.006) without additional toxicities. This intervention led to adequate exposure in 15 patients (83%). Seventeen patients had all Cmin levels ≥ 8.4 ng/mL, in these patients mean Cmin was 31.5 (65%) ng/mL. Conclusions: TDM of abiraterone was applied in clinical practice and proved to be feasible. Concomitant intake with food resulted into a significant increase in Cmin and offers a cost-neutral opportunity to optimize treatment for patients with low PK exposure. Up to 100 patients will be included to evaluate the effect of PK-guided abiraterone dosing on treatment efficacy. Clinical trial information: NL6695.

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Real-life isoniazid and rifampicin plasma concentrations in children: a tool for therapeutic drug monitoring of tuberculosis

BMC Infectious Diseases ◽

10.1186/s12879-021-06764-7 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Chiara Tersigni ◽

Giulia Boiardi ◽

Lorenzo Tofani ◽

Elisabetta Venturini ◽

Carlotta Montagnani ◽

...

Keyword(s):

Plasma Concentration ◽

Therapeutic Drug Monitoring ◽

Drug Monitoring ◽

Venous Blood ◽

Plasma Concentrations ◽

Age Groups ◽

Real Life ◽

Therapeutic Drug ◽

Blood Samples ◽

Drug Concentrations

Abstract Background Low plasma levels of first-line antitubercular drugs can be counted among the main causes of poor response to antitubercular therapy, and therapeutic drug monitoring has been proposed as a method to promote tailored treatments for both child and adult patients. The main aim of the study was to evaluate serum concentrations of isoniazid (INH) and rifampicin (RIF) and to investigate reasons for sub-therapeutic plasma concentrations in order to fix dosages. Methods Children with TB were prospectively enrolled from January to August 2019. Two venous blood samples were collected (the first at least 15 days after the beginning of antitubercular treatment, and the second between 1 and 8 weeks later). Plasma concentrations were determined by a validated high-performance liquid chromatography method. Results In all, 45 children were included. Seventy blood samples for INH plasma concentration were collected between 120 and 240 min after drug intake. Adjusting for dose (mg/kg/day) and time of INH administration, when considering three different age groups (≤ 2 years, 2–12 years, > 12 years), a statistically significant lower INH plasma concentration was observed in younger children compared to the older age groups in the multivariate analysis (p < 0.001 and p < 0.001). A total of 68 blood samples were evaluated for RIF concentrations. Both for INH and RIF a statistically significant lower plasma concentration was also observed in adolescents (p < 0.001). Fifteen children (15/45, 33%) presented drug concentrations under the referral therapeutic range. Conclusions Based on our findings, monitoring patients’ drug plasma concentrations in children under 2 years of age and in adolescents can make treatment more patient-tailored.

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