%0 Journal Article
%T Remedial Dosing Recommendations for Sirolimus Delayed or Missed Dosages Caused by Poor Medication Compliance in Pediatric Tuberous Sclerosis Complex Patients.
%A Yang Y
%A Jiang L
%A Zhu HR
%A Sun WX
%A Mao JY
%A Miao JW
%A Wang YC
%A He SM
%A Wang DD
%A Chen X
%J Curr Pharm Des
%V 30
%N 11
%D 2024 Mar 6
%M 38454763
%F 3.31
%R 10.2174/0113816128299479240213151714
%X BACKGROUND: Delayed or missed dosages caused by poor medication compliance significantly affected the treatment of diseases in children.
OBJECTIVE: The present study aimed to investigate the influence of delayed or missed dosages on sirolimus pharmacokinetics (PK) in pediatric tuberous sclerosis complex (TSC) patients and to recommend remedial dosages for nonadherent patients.
METHODS: A published sirolimus population PK model in pediatric TSC patients was used to assess the influence of different nonadherence scenarios and recommend optimally remedial dosages based on Monte Carlo simulation. Thirteen nonadherent scenarios were simulated in this study, including delayed 2h, 4 h, 6 h, 8 h, 10 h, 12 h, 14 h, 16 h, 18 h, 20 h, 22 h, 23.5 h, and missed one dosage. Remedial dosing strategies contained 10-200% of scheduled dosages. The optimal remedial dosage was that with the maximum probability of returning the individual therapeutic range.
RESULTS: For delayed or missed sirolimus dosages in pediatric TSC patients, when the delayed time was 0-8 h, 8-10 h, 10-18 h, 18-22.7 h, 22.7-24 h, 70%, 60%, 40%, 30%, 20% scheduled dosages were recommended to take immediately. When one dosage was missed, 120% of scheduled dosages were recommended at the next dose.
CONCLUSIONS: It was the first time to recommend remedial dosages for delayed or missed sirolimus therapy caused by poor medication compliance in pediatric TSC patients based on Monte Carlo simulation. Meanwhile, the present study provided a potential solution for delayed or missed dosages in clinical practice.