Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/20402
Title: PHARMACODYNAMICS, PHARMACOKINETICS AND PHARMACOGENETICS OF DOXORUBICIN IN SINGAPOREAN BREAST CANCER PATIENTS
Authors: FAN LU
Keywords: Pharmacodynamics, Pharmacokinetics, Pharmacogenetics, Doxorubicin, breast cancer
Issue Date: 8-Sep-2009
Source: FAN LU (2009-09-08). PHARMACODYNAMICS, PHARMACOKINETICS AND PHARMACOGENETICS OF DOXORUBICIN IN SINGAPOREAN BREAST CANCER PATIENTS. ScholarBank@NUS Repository.
Abstract: Doxorubicin is a cytotoxic drug with potential for severe myelosuppression that is highly variable and poorly predictable. We correlated pharmacokinetics and pharmacogenetics (CBR1 and CBR3 genotypes) with the pharmacodynamics of doxorubicin in 99 Singaporean breast cancer patients receiving the first-line doxorubicin. We found that the patient¿s body surface area was not associated with the pharmacokinetics and pharmacodynamics of doxorubicin. However, the leucocyte suppression at nadir was negatively correlated with the plasma concentration ratios of doxorubicinol to doxorubicin at 1 hr; whereas the doxorubicin-induced tumour reduction was negatively related to the pharmacokinetics parameter, K21. A common non-synonymous variant, CBR3 C4Y (11G>A), was associated with lower doxorubicin metabolic ratio of doxorubicinol AUC to doxorubicin AUC and lower intra-tumoral CBR3 expression, and consistently greater leucocyte suppression at nadir and greater tumor reduction. Chinese had higher frequency of the CBR3 C4Y (11G>A) variant than Indians. It may account for that Chinese patients experienced greater degree of hematologic toxicities than Indians. The reported functional allele CBR3 V244M (730G>A) and the intronic variant CBR1 397+125G>T had significantly higher doxorubicinol AUC. In conclusion, the analysis of PK and PG of CBRs could provide useful information for individualized chemotherapy with doxorubicin.
URI: http://scholarbank.nus.edu.sg/handle/10635/20402
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