scholarly journals Population Pharmacokinetic Study of a Test Dose Busulfan Patients Undergoing Hematopoietic Stem Cell Transplantation

2013 ◽  
Vol 19 (2) ◽  
pp. S265
Author(s):  
Iracema Esteves Nogueira ◽  
Juliana Fernandes ◽  
Eduardo K. Sugawara ◽  
Jose Salvador de Oliveira ◽  
Roseane Gouveia ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Pharmacokinetic Study ◽  
Test Dose ◽  
Population Pharmacokinetic ◽  
Hematopoietic Stem ◽  
Population Pharmacokinetic Study

Target Dose Adjustment of Oral Busulfan Using a Test Dose in Japanese Adults Undergoing Hematopoietic Stem Cell Transplantation.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5313-5313
Author(s):  
Yasushi Takamatsu ◽  
Kentaro Ogata ◽  
Noriaki Sasaki ◽  
Shuuji Hara ◽  
Tetsuya Eto ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Dose Adjustment ◽  
Prospective Trial ◽  
Conditioning Regimen ◽  
Test Dose ◽  
Hematopoietic Stem

Abstract Oral busulfan (BU) is widely used in patients undergoing hematopoietic stem cell transplantation (HST). Therapeutic effect of BU is related to the area under the plasma concentration-time curve (AUC) or the average plasma concentrations at steady state (Css). It has been shown that BU pharmacokinetics (PK) are highly variable and the dose adjustment according to the BU levels is critical to get the successful results of HST for Caucasians. BU is metabolized mainly in the liver through conjugation with glutathione by glutathione S-transferase (GST). Recent study has shown that the polymorphisms of GST genes are associated with the risk of developing hepatic veno-occlusive disease in patients undergoing HST. Ethnic variation is also demonstrated in relation to a gene deletion polymorphism of GST, suggesting that BU metabolism is influenced by the race. BU PK have been extensively investigated in Caucasians and few studies have focused on Asian people. We therefore underwent a prospective trial of adjusting BU doses depending on the individual BU PK in 36 Japanese patients aged from 16 to 64 years (median; 47 years). All patients received a busulfan-containing conditioning regimen and underwent allogeneic HST. Individual PK were studied following a 0.5 mg/kg test dose of BU administered orally. BU concentrations were measured by a high-performance liquid chromatographic method and individual PK parameters of BU were calculated with a one-compartment model by using Bayesian modeling program. The median clearance (CL/F) was 0.16 L/hr/kg (0.09 to 0.34 L/hr/kg), the median volume of distribution (Vd/F) 0.65 L/kg (range; 0.41 to 0.97 L/kg), the median elimination half-life (t1/2) 2.9 hr (range; 1.9 to 7.0 hr), and the median absorption rate constant (ka) 2.46 /hr (range; 0.53 to 6.03 /hr). BU doses were adjusted to achieve a target BU Css between 800 and 900 ng/mL. Twenty-six (72%) patients were required to reduce BU doses and adjusted BU doses ranged from 0.51 to 1.29 mg/kg/time (median; 0.85 mg/kg/time). After administrating the 6th dose of BU for the conditioning regimen, BU PK were analyzed. Expected Css was significantly correlated with observed Css and predictability of the test dose was 106.4±21.8%. Engraftment was successful in 34 of 36 (94%) patients. Grade 2 to 4 regimen-related toxicity except stomatitis occurred in 4 (11%) patients. These data demonstrate that BU PK vary widely from one patient to another after oral BU in Japanese and individualization of BU doses depending on the BU PK are useful in improving clinical outcome in patients undergoing HST.

Pre-Transplant Test Dose vs. PK Studies during Conditioning Regimen To Target iv Busulfan in Allogeneic Hematopoietic Stem Cell Transplantation.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3006-3006
Author(s):  
Sandeep Chunduri ◽  
Rakesh Beri ◽  
Lisa C. Dobogai ◽  
Elizabeth Hurter ◽  
Christina Mactal-Haaf ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Conditioning Regimen ◽  
Test Dose ◽  
Hematopoietic Stem ◽  
Blood Samples ◽  
The Mean

Abstract In this study we tested the efficacy of a test dose of iv busulfan in targeting blood levels of this drug during the conditioning regimen prior to an allogeneic hematopoietic stem cell transplant. We analyzed blood samples of 22 patients undergoing allogeneic hematopoietic stem cell transplantation with a busulfan-based conditioning regimen. Patients received a test dose of busulfan at 0.8 mg/kg as a 60 minute intravenous infusion. Serial blood samples were drawn at eight time points: 15 minutes before dose, at end of infusion, 15 minutes after completion, 30 minutes after completion, 60 minutes after completion, 2 hours after completion, 4 hours after completion, and 6 hours after completion. Pharmacokinetics (PK) studies were then performed at the Seattle Cancer Care pharmacokinetics laboratory. The AUC was determined using WinNonlin Professional software. The conditioning dose of busulfan was calculated by multiplying the test dose in mg/AUC × 4800. After the first dose of busulfan was administered, the same protocol was used to test busulfan PK. If the Busulfan AUC was therapeutic (between 4800 μM*min and 5200 μM*min) then the same dose was continued. If the Busulfan AUC was low or high then the third and fourth doses of busulfan were adjusted. The test dose of 0.8 mg/kg intravenous did not have any hematological side effects. The mean historic dose (solely based on weight) was 3.2 ± 0.1 mg/kg and the mean dose based on the test dose was 3.5 ± 0.5 mg/kg (p=0.02). In 12 patients where we also analyzed PK after the first day of conditioning regimen, AUC values of busulfan obtained during test dose and after day 1 dose were not different (p=0.7). The mean dose of busulfan based on test dose was 3.5 ± 0.6 mg/kg while the final dose based on day 1 busulfan PK was 3.6 ± 0.7 mg/kg (p=0.9). Nevertheless, in 2 CML patients who were on treatment with dasatinib or nilotinib at the time of the test dose, a higher AUC was observed (AUC 6065 and 6200, respectively). A pre-transplant busulfan test dose can be safely performed anytime prior to transplant and allows targeting the dose of busulfan efficiently, thus avoiding the requirement of PK studies during the conditioning regimen.

Prospective pharmacokinetic study of intravenous busulfan in hematopoietic stem cell transplantation in 25 children

2014 ◽  
Vol 18 (3) ◽  
pp. 294-301 ◽  
Author(s):  
Yasuhiro Okamoto ◽  
Yoshihisa Nagatoshi ◽  
Yoshiyuki Kosaka ◽  
Akira Kikuchi ◽  
Shunichi Kato ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Pharmacokinetic Study ◽  
Hematopoietic Stem
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