Title:Remedial Dosing Recommendations for Sirolimus Delayed or Missed Dosages
Caused by Poor Medication Compliance in Pediatric Tuberous Sclerosis
Complex Patients
Volume: 30
Issue: 11
Author(s): Yang Yang, Lei Jiang, Hai-Rong Zhu, Wen-Xin Sun, Jing-Yu Mao, Jing-Wen Miao, Yi-Chen Wang, Su-Mei He*, Dong-Dong Wang*Xiao Chen*
Affiliation:
- Department of Pharmacy, Suzhou Hospital, Affiliated Hospital
of Medical School, Nanjing University, Suzhou, Jiangsu 215153, China
- Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, School of
Pharmacy, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China
- School of Nursing, Xuzhou Medical
University, Xuzhou, Jiangsu 221004, China
Keywords:
Remedial dosing recommendations, sirolimus, delayed or missed dosages, poor medication compliance, pediatric tuberous sclerosis complex, pharmacokinetics.
Abstract:
Background: Delayed or missed dosages caused by poor medication compliance significantly affected
the treatment of diseases in children.
Aims: 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.
Conclusion: 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.
