Busulfex (i.v. BU) and CY regimen before SCT: Japanese-targeted phase II pharmacokinetics combined study

Kim, S. W.; Mori, Shinichiro; Tanosaki, Ryuji; Fukuda, Takahiro; Kami, Masahiro; Sakamaki, Hisashi; Yamashita, Toshinari; Kodera, Yoshihisa; Terakura, Seitaro; Taniguchi, Satoshi; Miyakoshi, S.; Usui, Noriko; Yano, Shingo; Kawano, Yoshifumi; Nagatoshi, Yashihisa; Harada, Mine; Morishima, Yasuo; Okamoto, Shinichiro; Saito, Akiko; Ohashi, Yasuo; Ueda, Ryuzo; Takaue, Yoichi

doi:10.1038/bmt.2008.372

Cited by 10 publications

(13 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Written informed consent was obtained from all subjects prior to treatment drug administration. All subjects involved in this analysis had been involved in previously reported clinical studies …”

Section: Methodsmentioning

confidence: 99%

“…Of the 54 patients, 28 were pediatric patients (median age: 7.2 years; range: 0.3‐17.7 years). A summary of the study data included in the analysis and characteristics of the patient population are shown in Table …”

Section: Methodsmentioning

confidence: 99%

“…All subjects involved in this analysis had been involved in previously reported clinical studies. 9,25…”

Section: Methodsmentioning

confidence: 99%

“…The data used for analysis were obtained from 54 patients who underwent stem cell transplantation and received Q6H dosing with intravenous (IV) busulfan in a phase 2 trial and a postmarketing clinical trial. 9,25 Of the 54 patients, 28 were pediatric patients (median age: 7.2 years; range: 0.3-17.7 years). A summary of the study data included in the analysis and characteristics of the patient population are shown in Table 1.…”

Section: Study Populationmentioning

confidence: 99%

“…2 In the present analysis, a busulfan PopPK model 22 superior to the Bartelink 2-compartment model 21 was used, with a maturation function included in the model to analyze Japanese patient busulfan data integrating postmarketing pediatric clinical trial data 9 and adult phase 2 trial data. 25 The objectives of the analysis were (1) to perform PopPK analysis using Japanese patient data as described above, (2) to confirm that there are no major racial differences in busulfan pharmacokinetics between Japanese and non-Japanese patients, and (3) to predict the under-the-steady-state concentration-time curve (AUC ss ) and concentration (C av,ss ) of busulfan for once-daily dosing based on Q6H dosing data and evaluate whether the predicted AUCs are within the busulfan therapeutic window. --Data presented as number (%) or mean ± SD.…”

mentioning

confidence: 99%

See 4 more Smart Citations

Population Pharmacokinetic Analysis of Busulfan in Japanese Pediatric and Adult HCT Patients

Kawazoe

Funaki

Kim

2018

The Journal of Clinical Pharma

View full text Add to dashboard Cite

Busulfan is the most common chemotherapy agent used in allogeneic hematopoietic cell transplant (HCT) conditioning regimens. As narrow therapeutic index and interpatient variability exists in the effectiveness and toxicity of conditioning regimens, personalizing intravenous busulfan therapy is desirable. Population pharmacokinetic-based approaches have been applied to therapeutic drug monitoring for the purpose of personalizing therapy. A population pharmacokinetic analysis with the objective of personalizing therapy in Japanese patients was conducted by integrating pediatric patient data with adult patient data. McCune's model, a 2-compartment model that includes maturation of clearance and allometric scaling of clearance and volume of distribution, was used for the analysis. McCune's model could precisely describe the Japanese data, and the estimated parameters were similar to McCune's results for non-Japanese, indicating that there are no racial differences in busulfan pharmacokinetics. Using this model, the plasma concentrations for once-daily dosing were simulated to adapt new dosage regimens for the benefit and convenience of both patients and medical staff. The predicted busulfan concentrations were within the therapeutic range.

show abstract

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

“…All subjects involved in this analysis had been involved in previously reported clinical studies. 9,25…”

Section: Methodsmentioning

confidence: 99%

Section: Study Populationmentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Population Pharmacokinetic Analysis of Busulfan in Japanese Pediatric and Adult HCT Patients

Kawazoe

Funaki

Kim

2018

The Journal of Clinical Pharma

View full text Add to dashboard Cite

show abstract

Comparison of levetiracetam with phenytoin for the prevention of intravenous busulfan-induced seizures in hematopoietic cell transplantation recipients

Akiyama

Kume

Fukaya

et al. 2018

Cancer Chemother Pharmacol

View full text Add to dashboard Cite

PurposeBusulfan is used as a conditioning regimen for hematopoietic stem cell transplantation and is known to cause seizures as a side effect. As various anticonvulsant drugs have been reported, we conducted a retrospective investigation regarding the preventive effects and adverse events associated with different anticonvulsants administered alongside intravenous busulfan (ivBu) in our institution.MethodsWe targeted 104 patients who received ivBu at our institution from May 1, 2010 to April 30, 2017. We investigated the seizure prevention rate and adverse events rate under anticonvulsant prophylaxis.ResultsThere were 70 cases (67.3%) of phenytoin administration and 34 cases (32.7%) of levetiracetam administration for anticonvulsant therapy. The seizure prevention rate was 98.6% for phenytoin and 100% for levetiracetam; seizures occurred in one out of 104 patients. There were no significant differences in the seizure prevention rate depending on the type of anticonvulsant. Further, there were no differences in adverse events.ConclusionsAnticonvulsant prophylaxis is considered necessary for safe conditioning with ivBu. Adverse events associated with the use of levetiracetam are within an acceptable range. Further, levetiracetam is considered useful as a preventive drug against seizures during ivBu administration because it is easy to administer and has ideal pharmacokinetics for supportive care.

show abstract

Pharmacokinetics study of once-daily intravenous busulfan in conditioning regimens for hematopoietic stem cell transplantation

et al. 2015

View full text Add to dashboard Cite

In Japan, intravenous busulfan (ivBu) is usually given four times per day as an infusion at 0.8 mg/kg over 2 h. However, as this requires a midnight administration, a once-daily infusion of ivBu at 3.2 mg/kg over 3 h has been investigated as a more convenient and safer method. In this study, 20 Japanese patients received once-daily ivBu in conditioning regimens before allogeneic hematopoietic stem cell transplantation (HSCT), and blood samples were obtained just before, and 3, 3.5, 5, 7, 10, and 24 h after the initiation of ivBu infusion. The outcomes of HSCT were evaluated prospectively. The median area under the plasma concentration versus time curve (AUC) of Bu was 5272 μmol × min/L (range 3491-6284 μmol × min/L), and was similar to those in previous once-daily ivBu studies and to the estimated daily AUC in previous 4-times-daily ivBu studies. All of the patients but two, who died early due to infection, achieved neutrophil engraftment at a median of 25 days after transplantation. No patient was diagnosed with veno-occlusive disease according to the criteria established by Jones. No regimen-related toxicity was significantly associated with AUC. In conclusion, once-daily administration of ivBu has a stable pharmacokinetic profile, and was safely performed in Japanese patients.

show abstract

Busulfex (i.v. BU) and CY regimen before SCT: Japanese-targeted phase II pharmacokinetics combined study

Cited by 10 publications

References 25 publications

Population Pharmacokinetic Analysis of Busulfan in Japanese Pediatric and Adult HCT Patients

Population Pharmacokinetic Analysis of Busulfan in Japanese Pediatric and Adult HCT Patients

Comparison of levetiracetam with phenytoin for the prevention of intravenous busulfan-induced seizures in hematopoietic cell transplantation recipients

Pharmacokinetics study of once-daily intravenous busulfan in conditioning regimens for hematopoietic stem cell transplantation

Contact Info

Product

Resources

About