Kinetic of Genotoxic Expression in the Pharmacodynamics of Busulfan

“…Busulfan is a bi-functional alkylating agent that rapidly (i.e., within 2 minutes) damages DNA in a dose-dependent manner ex vivo (Morales-Ramirez et al 2006). Busulfan plasma exposure has proven to be a predictive marker for outcomes, and PK-guided busulfan dosing has been shown to lower rates of rejection, nonrelapse mortality, and relapse in select HCT recipients (Deeg et al 2006; Radich et al 2003).…”

Section: Discussionmentioning

confidence: 99%

Prediction of intravenous busulfan clearance by endogenous plasma biomarkers using global pharmacometabolomics

et al. 2016

View full text Add to dashboard Cite

Introduction High-dose busulfan (busulfan) is an integral part of the majority of hematopoietic cell transplantation conditioning regimens. Intravenous (IV) busulfan doses are personalized using pharmacokinetics (PK)-based dosing where the patient’s IV busulfan clearance is calculated after the first dose and is used to personalize subsequent doses to a target plasma exposure. PK-guided dosing has improved patient outcomes and is clinically accepted but highly resource intensive. Objective We sought to discover endogenous plasma biomarkers predictive of IV busulfan clearance using a global pharmacometabolomics-based approach. Methods Using LC-QTOF, we analyzed 59 (discovery) and 88 (validation) plasma samples obtained before IV busulfan administration. Results In the discovery dataset, we evaluated the association of the relative abundance of 1885 ions with IV busulfan clearance and found 21 ions that were associated with IV busulfan clearance tertiles (r2 ≥ 0.3). Identified compounds were deoxycholic acid and/or chenodeoxycholic acid, and linoleic acid. We used these 21 ions to develop a parsimonious seven-ion linear predictive model that accurately predicted IV busulfan clearance in 93% (discovery) and 78% (validation) of samples. Conclusion IV busulfan clearance was significantly correlated with the relative abundance of 21 ions, seven of which were included in a predictive model that accurately predicted IV busulfan clearance in the majority of the validation samples. These results reinforce the potential of pharmacometabolomics as a critical tool in personalized medicine, with the potential to improve the personalized dosing of drugs with a narrow therapeutic index such as busulfan.

show abstract

“…Busulfan, a form of nitrogen mustard, is a bifunctional drug that intercalates cytosine, develops sulfur bridges with DNA, binds to RNA and disrupts proteins. It is therefore capable of producing mono-adducts, intrastrand cross-links, and cross-links of DNA-protein [11][12] that are thought to play an important role in its toxic and carcinogenic effects [13][14].…”

Section: Specifications Informationmentioning

confidence: 99%

HPLC method for the development and validation of busulfan in pharmaceutical formulation

Sekhar¹,

kishore²,

Rao³

et al. 2021

GSC Adv. Res. Rev.

View full text Add to dashboard Cite

A validated HPLC method was developed for the determination of Busulfan (BUS) in pharmaceutical formulation.It is a new simple, accurate, precise and reproducible HPLC method has been developed for the estimation of Busulfan (1,4-butanediol dimethanesulfonate) in its inject able dosage.The method developed in High Performance Liquid Chromatographic method using suitable column (YMC Pack ODS-A (150 x 4.6) mm, 3µm). All the components of the system are controlled using SCL-10Avp System Controller. Data acquisition was done using LC Solutions software.The method was validated as per the ICH guidelines. Thus, the proposed HPLC method can be successfully applied for the routine quality control analysis of formulations. The method developed is simple and is better than the methods reported in the literature and the method is capable to give a good detector response, the recovery calculated was within the range of 98% to 102% of the specification limits.

show abstract

Kinetic of Genotoxic Expression in the Pharmacodynamics of Busulfan

Cited by 10 publications

References 21 publications

Combinations of genotoxic tests for the evaluation of group 1 IARC carcinogens

Combinations of genotoxic tests for the evaluation of group 1 IARC carcinogens

Prediction of intravenous busulfan clearance by endogenous plasma biomarkers using global pharmacometabolomics

HPLC method for the development and validation of busulfan in pharmaceutical formulation

Contact Info

Product

Resources

About