Multicenter-Based Population Pharmacokinetic Analysis of Ciclosporin in Hematopoietic Stem Cell Transplantation Patients

Xue, Liang; Zhang, Wenjuan; Tian, Ji-Xin; Liu, Linna; Yan, Huimin; Zhang, Wen; Ding, Xiaoliang; Zhang, Jingjing; Miao, Liyan

doi:10.1007/s11095-019-2740-2

Cited by 8 publications

(17 citation statements)

References 42 publications

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“…Interpatient variability in the V could not be estimated due to inadequate samples during the distribution phase. The estimated CL was 19.8 L/h, which agrees with that reported in other studies, in a range of 21.2–31.0 L/h 5–7,16–19,27 . The estimated V was 1340 L, which was higher than that reported in previous studies (range from 192 to 1080 L) 5–7,16–19,27 .…”

Section: Discussionsupporting

confidence: 89%

“…The estimated CL was 19.8 L/h, which agrees with that reported in other studies, in a range of 21.2–31.0 L/h 5–7,16–19,27 . The estimated V was 1340 L, which was higher than that reported in previous studies (range from 192 to 1080 L) 5–7,16–19,27 . These discrepancies in CsA distribution might be due in part to the difference in the structural pharmacokinetic model and racial or regional difference among the study population.…”

Section: Discussionsupporting

confidence: 87%

“…25 CsA exposure. 26 In this study, 85.8% of the concentrations of CsA [5][6][7][16][17][18][19]27 The estimated V was 1340 L, which was higher than that reported in previous studies (range from 192 to 1080 L). [5][6][7][16][17][18][19]27 These discrepancies in CsA distribution might be due in part to the difference in the structural pharmacokinetic model and racial or regional difference among the study population.…”

Section: Discussioncontrasting

confidence: 76%

“…Population pharmacokinetic analysis is a strategy that can be employed to identify the mean pharmacokinetic parameters and their variations, to identify significant covariates, and to establish the optimal dosage regimen. Until now, a certain amounts of population pharmacokinetic models have been constructed to help explain the variability of CsA pharmacokinetics in allo‐HSCT patients 5–7,16–19 . Even though some covariates including demographic characteristics, HCT, postoperative day, renal and liver function, and co‐administration of azole antifungal drugs are identified, the unexplained variability of CsA pharmacokinetics remains relatively high.…”

Section: Discussionmentioning

confidence: 99%

“…The model was parameterized using absorption rate constant (k a ), clearance (CL), volume of distribution (V) and bioavailability (F). Because the retrospective data set was constituted solely by trough concentration and there were no data from the absorption phase, k a was fixed at 1.25 h −1 according to a previous report 7 …”

Section: Methodsmentioning

confidence: 99%

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Population pharmacokinetics of ciclosporin in allogeneic hematopoietic stem cell transplant recipients: C‐reactive protein as a novel covariate for clearance

Ling

Yang

Dong

et al. 2021

Clinical Pharmacy Therapeu

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What is known and objectives Ciclosporin (CsA), a potent immunosuppressive agent used to prevent graft‐versus‐host disease in allogeneic hematopoietic stem cell transplant (allo‐HSCT) recipients, is characterized by large inter‐individual variability and a narrow therapeutic range. The aim of this study was to develop a population pharmacokinetic model for CsA in Chinese allo‐HSCT recipients and to identify covariates influencing CsA pharmacokinetics. Methods A total of 758 retrospective drug monitoring data points were collected after intravenous infusion or oral administration of CsA from 59 patients. Population pharmacokinetic analysis was performed using nonlinear mixed effects modelling expressed by differential equations. Monte Carlo simulation was applied to optimize dosage regimens. The final model was validated using bootstrap and normalized prediction distribution errors. Results and discussion The results showed that the daily CsA dose, haematocrit, total bile acid, C‐reactive protein (CRP) and co‐administration of triazole antifungal agent were identified as significant covariates for clearance (CL) of CsA. The typical value of CL was 19.8 L/h with an inter‐individual variability of 13.1%. The volume of distribution was 1340 L. Bioavailability was 67.2% with an inter‐individual variability of 8.5%. Dosing simulation based on the developed model indicated that patients with high CRP concentration required a higher daily dose to attain the therapeutic trough concentration. The influence of CRP ultimately on the therapy outcome of CsA is not clear, which needs further study. What is new and conclusion CRP concentration was identified as a novel marker associated with CsA pharmacokinetics, which should be considered when determining the appropriate dosage of CsA in allo‐HSCT recipients.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionsupporting

confidence: 87%

Section: Discussioncontrasting

confidence: 76%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 3 more Smart Citations

Population pharmacokinetics of ciclosporin in allogeneic hematopoietic stem cell transplant recipients: C‐reactive protein as a novel covariate for clearance

Ling

Yang

Dong

et al. 2021

Clinical Pharmacy Therapeu

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Effect of posaconazole on the concentration of intravenous and oral cyclosporine in patients undergoing hematopoietic stem cell transplantation

Zhu

Huang

Cai

et al. 2022

Eur J Clin Pharmacol

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This study aimed to investigate the interactions between posaconazole (POS) and intravenously/orally administered Cyclosporine A (CsA) in allogeneic hematopoietic stem cell transplant (HSCT) recipients. MethodsWe included 118 allogeneic HSCT patients who received CsA and POS simultaneously between January 2017 and June 2020 this study. The ratio of CsA blood concentration (ng/mL) to dosage (mg/day) (C/D) before and after POS initiation was compared. ResultsAfter the initiation of POS, the level of CsA increased 1 to 2 times in 66% (78/118) of patients compared to those without POS. However, the CsA C/D ratio increased by more than threefold in 6% (7/118) of patients after POS initiation, with an increase of more than fourfold in two patients. The median C/D ratio of CsA increased from 0.89 to 1.23 (P < 0.001) and 0.78 to 1.22 (P < 0.001) after POS initiation when CsA was administered intravenously and orally, respectively. In patients who received POS at the time of transition from intravenous to oral CsA, the value increased from 1.01 to 1.38 (P = 0.001). The route of administration had no signi cant effect on the change in the CsA C/D ratio (P = 0.615). Additionally, we observed the time required for the C/D ratio to reach a plateau after POS initiation was similar on days 13, 8, and 15 under various scenarios. ConclusionPOS treatment increased blood CsA levels. A large variability was found in the fold-change in the CsA C/D ratio. Therefore, CsA doses should be adjusted by closely monitoring the blood levels of CsA after POS initiation.

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Population pharmacokinetics of cyclosporine A in pediatric patients with thalassemia undergoing allogeneic hematopoietic stem cell transplantation

Cai,

Zhang,

et al. 2024

Eur J Clin Pharmacol

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Multicenter-Based Population Pharmacokinetic Analysis of Ciclosporin in Hematopoietic Stem Cell Transplantation Patients

Cited by 8 publications

References 42 publications

Population pharmacokinetics of ciclosporin in allogeneic hematopoietic stem cell transplant recipients: C‐reactive protein as a novel covariate for clearance

Population pharmacokinetics of ciclosporin in allogeneic hematopoietic stem cell transplant recipients: C‐reactive protein as a novel covariate for clearance

Effect of posaconazole on the concentration of intravenous and oral cyclosporine in patients undergoing hematopoietic stem cell transplantation

Population pharmacokinetics of cyclosporine A in pediatric patients with thalassemia undergoing allogeneic hematopoietic stem cell transplantation

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