Phenotyping study of cyclophosphamide 4-hydroxylation in malay cancer patients

Background: Cyclophosphamide (CP) is an anticancer alkylating group (nitrogen mustard) and a prodrug that will be metabolized to form its active metabolite, 4-hydroxycyclophosphamide (4-OHCP). The various enzymes involved in its bioactivation can cause a wide range of CP expression and activity among patients and ultimately affect the metabolism, efficacy and toxicity of this drug. The effectiveness of CP therapy can be determined by 4OHCP level in dried blood spot (DBS). Aim: The purpose of this study was to conduct the phenotyping of CP 4-hydroxylation rate in Malay cancer patients. Methodology: Phenotyping study of CP 4-hydroxylation rate to 40 subjects of Malay cancer patients was done based on the value of its bioactivity ratio (4-OHCP to CP levels). Results: The result shown the cyclophosphamide 4-hydroxylation rate of 80% (n=32) subjects as ultrarapid metabolizer (UM) and 20% (n=8) as poor metabolizer (PM). Conclusion: Phenotyping study of CP 4-hydroxylation in Malay cancer patients can be conducted by quantifying CP bioactivity ratio (4-OHCP to CP level) in dried blood spot. In majority of Malay cancer patients, cyclophosphamide would be bioactivated through 4hydroxylation in hepar rapidly as indicated by the high value of the bioactivity ratio or the increased CP clearance and 4-OHCP level.