Aim
The aim of this pharmacokinetic (PK) study was to evaluate tacrolimus (TAC) exposure in stable cystic fibrosis (CF) lung transplant (LT) recipients, converted from TAC twice daily to TAC once ...daily in an open-label, prospective, single-centre study.
Methods
Eligible patients were post-transplant CF patients (18–65 years) with stable lung function, on stable doses of TAC twice daily and who were candidates to switch to TAC once daily. Twelve consecutive patients were included in the study. Patients had their first PK analysis on day 1, still under the stable TAC twice-daily regimen, and were converted to TAC once daily from day 2 onwards. The doses were adjusted according to clinical judgement to achieve target levels, and a second 24-h PK period profile was obtained once the patient was on a stable dosage on the therapeutic range.
Results
The mean total (SD) daily dose of TAC twice daily at baseline upon enrolment was 0.17 (0.10) mg/kg/day. The mean (SD) daily dose of TAC once daily after adjustments was 0.22 (0.12) mg/kg/day. In order to achieve target
C
min
levels with a similar AUC
0–24
, 82 % of subjects who were converted to TAC once daily required an increase of dose, in a range of 0–66.7 %, with a mean dose increase of 28 %.
Conclusions
Our study results indicate that the switch for conversion from TAC twice daily to TAC once daily in patients with CF may need dose adjustment in order to reach levels within the therapeutic target.
This study aimed to describe the prevalence of corrected QT (QTc) interval disorders and the possible predisposing factors in children and adolescents treated with antipsychotic (AP) medications in a ...real-world population with a long-term follow-up.
Data were obtained from the SafEty of NeurolepTics in Infancy and Adolescence (SENTIA) registry (https://sentia.es). The SENTIA includes patients younger than 18 years who are currently taking or initiating treatment with AP medications and have agreed to participate in the registry. The SENTIA's follow-up includes an electrocardiogram (ECG) assessment before starting treatment and at 1, 3, and 6 months after treatment initiation or after any changes in the patient's AP medication treatment. Thereafter, all participants undergo an ECG every 6 months. A QTc interval more than 450 milliseconds, increases in QTc interval of 60 milliseconds or more, or QTc dispersion more than 100 milliseconds were considered abnormal.
Since January 1, 2011, 101 patients have been enrolled in SENTIA and have had at least 1 ECG assessment. The mean age at inclusion was 11.5 years; 75% of the patients were men. The mean follow-up time was 20.0 ± 15.1 months. The most frequently prescribed AP medications were risperidone (52.2%) and aripiprazole (45.5%). Seven patients (6.9%) had abnormal changes in QTc. No patient had a QTc interval more than 500 milliseconds. All patients were asymptomatic. The QTc changes were observed at different times of exposure, with a range of 1 to 39 months after beginning AP treatment. Concomitant use of attention deficit and hyperactivity disorder drugs seemed a possible factor associated with QTc disorders.
Patients should undergo a baseline ECG assessment before starting AP medication treatment, particularly patients with concomitant use of attention deficit and hyperactivity disorder drugs or a family/personal history of heart disease.
