Sang-Seokg Seong; Jae-Hee Yun; Eun Young Kim; Jae-Gook Shin; Jae-Bum Jun; Sang-Cheol Bae

doi:10.4078/jkra.2007.14.2.144

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Seong, Yun, Kim, Shin, Jun, and Bae: Severe Leukopenia after Intravenous Cyclophosphamide Pulse Therapy in a Patient Having Cytochrome P450 2A6∗1B

Original Article

J Korean Rheum Assoc 2007;14(2):144-148.

Published online: 23 June 2007

DOI: https://doi.org/10.4078/jkra.2007.14.2.144

Severe Leukopenia after Intravenous Cyclophosphamide Pulse Therapy in a Patient Having Cytochrome P450 2A6∗1B

Sang-Seokg Seong, M.D.^∗∗, Jae-Hee Yun, M.D., Eun Young Kim, M.D.^∗, Jae-Gook Shin, M.D.^∗, Jae-Bum Jun, M.D., Sang-Cheol Bae, M.D.

Department of Internal Medicine, The Hospital for Rheumatic Diseases, Hanyang University College of Medicine, Seoul, Korea

^∗Department of Pharmacology and Pharmacogenomics Research Center, Inje University College of Medicine, Busan, Korea

^∗∗Department of Internal Medicine, Konyang University, Daejeon, Korea

Received 19 December 200616 February 2007

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Cyclophosphamide, a prodrug requiring metabolic activation by cytochrome P450 (CYP) enzymes, is used widely for proliferative lupus nephritis and various CYP isoenzymes have been demonstrated to be involved in the bioactivation of cyclophosphamide in humans, including CYP2A6, 2B6, 2C19, 2C9, 3A4, and 3A5. The response or adverse event after intravenous cyclophosphamide pulse therapy in lupus nephritis patient seems to be different for each individual and genetic polymorphism of CYP may explain the difference. Generally, wild types of CYP seem to be more active in the activation of cyclophosphamide than variant types of CYP. Here, we report a case of lupus nephritis with a genotype of CYP2A6∗1 B who suffered from severe leukopenia after intravenous cyclophosphamide pulse therapy.

Keywords: Cyclophosphamide, Leukopenia, Cytochrome P450

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Fig. 1.

Time course of the values for leukocyte, neutrophil and 24 hour proteinuria. IC: intravenous cyclophosphamide pulse therapy, G-CSF: granulocyte colony stimulating factor. Leukocyte and neutrophil count are expressed in mm³ and proteinuria is expressed in mg/day.

Fig. 2.

Result of genotype. PCR-RFLP method was used for the analyses of CYP2A6, CYP2B6, CYP3A4, and CYP3A5. Pyrosequencing method for CYP2CP analysis and both method were used for CYP2C19 analysis. The patient had polymorphism in CYP2A6 and CYP3A5; CYP2A6∗1B/∗1B and CYP3A5∗3/∗3.

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