Population pharmacokinetics of sirolimus in pediatric patients with kaposiform hemangioendothelioma: A retrospective study

Wang,Dongdong; Chen,Xiao; Li,Zhiping

doi:10.3892/ol.2019.10562

Population pharmacokinetics of sirolimus in pediatric patients with kaposiform hemangioendothelioma: A retrospective study

Authors:
- Dongdong Wang
- Xiao Chen
- Zhiping Li
View Affiliations

Affiliations: Department of Pharmacy, Children's Hospital of Fudan University, Shanghai 201102, P.R. China
Published online on: July 4, 2019 https://doi.org/10.3892/ol.2019.10562
Pages: 2412-2419
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Numerous studies have established population pharmacokinetics (PPK) models of sirolimus in various populations. However, a PPK model of sirolimus in Chinese patients with pediatric kaposiform hemangioendothelioma (PKHE) has yet to be established; therefore, this was the purpose of the present study. The present study was a retrospective analysis that utilized the trough concentration data obtained from traditional therapeutic drug monitoring‑based dose adjustments. A total of 17 Chinese patients with PKHE from a real‑world study were characterized by non‑linear mixed‑effects modeling. The impact of demographic features, biological characteristics and concomitant medications was assessed. The developed final model was evaluated via bootstrap and a prediction‑corrected visual predictive check. A one‑compartment model with first‑order absorption and elimination was used for modeling of data for PKHE. The typical values of apparent oral clearance (CL/F) and apparent volume of distribution (V/F) in the final model were 3.19 l/h and 165 liters, respectively. Age, alanine transaminase levels and sex were included as significant covariates for CL/F, while the duration of treatment with sirolimus was a significant covariate for V/F. In conclusion, the present study developed and validated the first sirolimus PPK model for Chinese patients with PKHE.

View Figures

View References

1	Reichel A, Hamm H, Wiegering V, Wiewrodt B, Neubauer H, Ernestus K and Winkler B: Kaposiform hemangioendothelioma with Kasabach-Merritt syndrome: Successful treatment with sirolimus. J Dtsch Dermatol Ges. 15:329–331. 2017. View Article : Google Scholar
2	DeFatta RJ, Verret DJ, Adelson RT, Gomez A and Myers LL: Kaposiform hemangioendothelioma: Case report and literature review. Laryngoscope. 115:1789–1792. 2005. View Article : Google Scholar : PubMed/NCBI
3	Yasui N, Koh K, Kato M, Park MJ, Tomizawa D, Oshima K, Uchisaka N, Gocho Y, Arakawa A, Seki M, et al: Kasabach-Merritt phenomenon: A report of 11 cases from a single institution. J Pediatr Hematol Oncol. 35:554–558. 2013. View Article : Google Scholar : PubMed/NCBI
4	Croteau SE, Liang MG, Kozakewich HP, Alomari AI, Fishman SJ, Mulliken JB and Trenor CC III: Kaposiform hemangioendothelioma: Atypical features and risks of Kasabach-Merritt phenomenon in 107 referrals. J Pediatr. 162:142–147. 2013. View Article : Google Scholar : PubMed/NCBI
5	Yadav D, Maheshwari A, Aneja S, Seth A and Chandra J: Neonatal Kasabach-Merritt phenomenon. Indian J Med Paediatr Oncol. 32:238–241. 2011. View Article : Google Scholar : PubMed/NCBI
6	Blatt J, Stavas J, Moats-Staats B, Woosley J and Morrell DS: Treatment of childhood kaposiform hemangioendothelioma with sirolimus. Pediatr Blood Cancer. 55:1396–1398. 2010. View Article : Google Scholar : PubMed/NCBI
7	Iacobas I, Simon ML, Amir T, Gribbin CE, McPartland TG, Kaufman MR, Calderwood S and Nosher JL: Decreased vascularization of retroperitoneal kaposiform hemangioendothelioma induced by treatment with sirolimus explains relief of symptoms. Clin Imaging. 39:529–532. 2015. View Article : Google Scholar : PubMed/NCBI
8	Jahnel J, Lackner H, Reiterer F, Urlesberger B and Urban C: Kaposiform hemangioendothelioma with Kasabach-Merritt phenomenon: From vincristine to sirolimus. Klin Padiatr. 224:395–397. 2012. View Article : Google Scholar : PubMed/NCBI
9	Kai L, Wang Z, Yao W, Dong K and Xiao X: Sirolimus, a promising treatment for refractory Kaposiform hemangioendothelioma. J Cancer Res Clin Oncol. 140:471–476. 2014. View Article : Google Scholar : PubMed/NCBI
10	Adams DM, Trenor CC III, Hammill AM, Vinks AA, Patel MN, Chaudry G, Wentzel MS, Mobberley-Schuman PS, Campbell LM, Brookbank C, et al: Efficacy and safety of sirolimus in the treatment of complicated vascular anomalies. Pediatrics. 137:e201532572016. View Article : Google Scholar : PubMed/NCBI
11	Zimmerman JJ and Kahan BD: Pharmacokinetics of sirolimus in stable renal transplant patients after multiple oral dose administration. J Clin Pharmacol. 37:405–415. 1997. View Article : Google Scholar : PubMed/NCBI
12	MacDonald A, Scarola J, Burke JT and Zimmerman JJ: Clinical pharmacokinetics and therapeutic drug monitoring of sirolimus. Clin Ther. 22 (Suppl B):B101–B121. 2000. View Article : Google Scholar : PubMed/NCBI
13	Chevillard L, Sabo N, Tod M, Labat L, Chasport C, Chevaleyre C, Thibaut F, Barre J, Azuar J, Questel F, et al: Population pharmacokinetics of oral baclofen at steady-state in alcoholic-dependent adult patients. Fundam Clin Pharmacol. 32:239–248. 2018. View Article : Google Scholar : PubMed/NCBI
14	Marsot A, Michel F, Chasseloup E, Paut O, Guilhaumou R and Blin O: Phenobarbital in intensive care unit pediatric population: Predictive performances of population pharmacokinetic model. Fundam Clin Pharmacol. 31:558–566. 2017. View Article : Google Scholar : PubMed/NCBI
15	Wang DD, Lu JM, Li Q and Li ZP: Population pharmacokinetics of tacrolimus in paediatric systemic lupus erythematosus based on real-world study. J Clin Pharm Ther. 43:476–483. 2018. View Article : Google Scholar : PubMed/NCBI
16	Vadcharavivad S, Praisuwan S, Techawathanawanna N, Treyaprasert W and Avihingsanon Y: Population pharmacokinetics of tacrolimus in Thai kidney transplant patients: Comparison with similar data from other populations. J Clin Pharm Ther. 41:310–328. 2016. View Article : Google Scholar : PubMed/NCBI
17	Jiao Z, Shi XJ, Li ZD and Zhong MK: Population pharmacokinetics of sirolimus in de novo Chinese adult renal transplant patients. Br J Clin Pharmacol. 68:47–60. 2009. View Article : Google Scholar : PubMed/NCBI
18	Jonsson EN and Karlsson MO: Xpose-an S-PLUS based population pharmacokinetic/pharmacodynamic model building aid for NONMEM. Comput Methods Programs Biomed. 58:51–64. 1999. View Article : Google Scholar : PubMed/NCBI
19	Fasolo A and Sessa C: Current and future directions in mammalian target of rapamycin inhibitors development. Expert Opin Investig Drugs. 20:381–394. 2011. View Article : Google Scholar : PubMed/NCBI
20	Thomson AH and Whiting B: Bayesian parameter estimation and population pharmacokinetics. Clin Pharmacokinet. 22:447–467. 1992. View Article : Google Scholar : PubMed/NCBI
21	Kauffman RE and Kearns GL: Pharmacokinetic studies in paediatric patients. Clinical and ethical considerations. Clin Pharmacokinet. 23:10–29. 1992. View Article : Google Scholar : PubMed/NCBI
22	Emoto C, Fukuda T, Mizuno T, Schniedewind B, Christians U, Adams DM and Vinks AA: Characterizing the developmental trajectory of sirolimus clearance in neonates and infants. CPT Pharmacometrics Syst Pharmacol. 5:411–417. 2016. View Article : Google Scholar : PubMed/NCBI
23	Mizuno T, Fukuda T, Emoto C, Mobberley-Schuman PS, Hammill AM, Adams DM and Vinks AA: Developmental pharmacokinetics of sirolimus: Implications for precision dosing in neonates and infants with complicated vascular anomalies. Pediatr Blood Cancer. 642017.doi: 10.1002/pbc.26470. PubMed/NCBI
24	Mizuno T, Emoto C, Fukuda T, Hammill AM, Adams DM and Vinks AA: Model-based precision dosing of sirolimus in pediatric patients with vascular anomalies. Eur J Pharm Sci 109S. S124–S131. 2017. View Article : Google Scholar
25	Lampen A, Zhang Y, Hackbarth I, Benet LZ, Sewing KF and Christians U: Metabolism and transport of the macrolide immunosuppressant sirolimus in the small intestine. J Pharmacol Exp Ther. 285:1104–1112. 1998.PubMed/NCBI
26	Sattler M, Guengerich FP, Yun CH, Christians U and Sewing KF: Cytochrome P-450 3A enzymes are responsible for biotransformation of FK506 and rapamycin in man and rat. Drug Metab Dispos. 20:753–761. 1992.PubMed/NCBI
27	Yang JW, Liao SS, Zhu LQ, Zhao Y, Zhang Y, Sun XY, Rao W, Qu W, Li WZ and Sun LY: Population pharmacokinetic analysis of tacrolimus early after Chinese pediatric liver transplantation. Int J Clin Pharmacol Ther. 53:75–83. 2015. View Article : Google Scholar : PubMed/NCBI
28	Anderson BJ and Holford NH: Mechanism-based concepts of size and maturity in pharmacokinetics. Annu Rev Pharmacol Toxicol. 48:303–332. 2008. View Article : Google Scholar : PubMed/NCBI
29	Wang DD, Chen X and Li ZP: Wuzhi capsule and haemoglobin influence tacrolimus elimination in paediatric kidney transplantation patients in a population pharmacokinetics analysis: A retrospective study. J Clin Pharm Ther. Mar 12–2019.doi: 10.1111/jcpt.12828 (Epub ahead of print). View Article : Google Scholar
30	Wang D, Chen X, Xu H and Li Z: Population pharmacokinetics and dosing regimen optimisation of tacrolimus in Chinese pediatric hematopoietic stem cell transplantation patients. Xenobiotica. 1–8. 2019.(Epub ahead of print). View Article : Google Scholar
31	Wang D, Chen X and Li Z: Cyclosporin population pharmacokinetics in pediatric refractory nephrotic syndrome based on real-world studies: Effects of body weight and spirolactone administration. Exp Ther Med. 17:3015–3020. 2019.PubMed/NCBI
32	Zimmerman JJ: Exposure-response relationships and drug interactions of sirolimus. AAPS J. 6:e282004. View Article : Google Scholar : PubMed/NCBI
33	Dansirikul C, Morris RG, Tett SE and Duffull SB: A Bayesian approach for population pharmacokinetic modelling of sirolimus. Br J Clin Pharmacol. 62:420–434. 2006. View Article : Google Scholar : PubMed/NCBI
34	Tejani A, Alexander S, Ettenger R, Lerner G, Zimmerman J, Kohaut E and Briscoe DM: Safety and pharmacokinetics of ascending single doses of sirolimus (Rapamune, rapamycin) in pediatric patients with stable chronic renal failure undergoing dialysis. Pediatr Transplant. 8:151–160. 2004. View Article : Google Scholar : PubMed/NCBI
35	Emoto C, Fukuda T, Venkatasubramanian R and Vinks AA: The impact of CYP3A5*3 polymorphism on sirolimus pharmacokinetics: Insights from predictions with a physiologically-based pharmacokinetic model. Br J Clin Pharmacol. 80:1438–1446. 2015. View Article : Google Scholar : PubMed/NCBI
36	Wang M, Duan BL, Yuan YJ, Su X, Zheng H, Wang FS and Sun H: Population pharmacokinetic characteristics of sirolimus in healthy Chinese subjects and renal transplant patients. Int J Clin Pharmacol Ther. 54:433–441. 2016. View Article : Google Scholar : PubMed/NCBI
37	Mizuno T, Fukuda T, Christians U, Perentesis JP, Fouladi M and Vinks AA: Population pharmacokinetics of temsirolimus and sirolimus in children with recurrent solid tumours: A report from the Children's Oncology Group. Br J Clin Pharmacol. 83:1097–1107. 2017. View Article : Google Scholar : PubMed/NCBI