Amandine Remy, Albert Etingin, Paul Gavra, Facundo Garcia-Bournissen, Sandrine Essouri, Audrey Denoncourt, Thai Hoa Tran, Josée Dubois, Yves Théorêt, Niina Kleiber
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引用次数: 0
Abstract
Severe forms of vascular malformations (VM) can highly impact patients' quality of life and lead to life-threatening organ dysfunction. Numerous VM are caused by somatic activating mutations in the PI3K/AKT/mTOR signalling pathway. Alpelisib, a PIK3CA inhibitor was recently FDA-approved for paediatric PIK3CA-related overgrowth syndrome (PROS). However, an empiric and fixed dose of 50 mg was selected, irrespective of weight, in the absence of any pharmacokinetic (PK) data. We aim to report novel alpelisib PK data in children to support dosing decisions.
Nine patients with severe VM (PROS: n = 4, other VM: n = 5) were included. Mean age was 10.5 years (SD = 5.2 years), and mean weight was 43 kg (SD = 24 kg). AUC on the fixed dose of 50 mg/day was highly variable (mean = 7035 ng*h/mL, SD = 4057, CV = 58%). AUC was correlated with weight.
As short- and long-term adverse effects to alpelisib in children are unknown, a dosing based on PK data is urgently needed.
期刊介绍：
Published on behalf of the British Pharmacological Society, the British Journal of Clinical Pharmacology features papers and reports on all aspects of drug action in humans: review articles, mini review articles, original papers, commentaries, editorials and letters. The Journal enjoys a wide readership, bridging the gap between the medical profession, clinical research and the pharmaceutical industry. It also publishes research on new methods, new drugs and new approaches to treatment. The Journal is recognised as one of the leading publications in its field. It is online only, publishes open access research through its OnlineOpen programme and is published monthly.
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