RESUMO
INTRODUCTION: The CYP450 complex participates in the metabolism of ifosfamide, an antineoplastic drug used to treat solid tumors. CYP450 genes contain several single nucleotide polymorphisms (SNPs) that confer different activity towards the enzyme. The aim of our study was to analyze gene frequencies of allelic variants and their association with ifosfamide blood levels and patient prognosis. MATERIAL AND METHODS: 148 DNA samples from children were analyzed. Genotyping was performed by real-time PCR with TaqMan probes and ifosfamide levels were determined in dried blood drop by UPLCMS/MS. RESULTS: Ifosfamide levels increased according to the genotype, and patients with the variant rs1799853 in CYP2C9 genotype CC had lower levels of ifosfamide (median = 1.8 µmol/l, Q25 0.9-Q75 4.6) compared with patients with genotype TT + CT (median = 2.8 µmol/l, Q25 1.9-Q75 5.1), p < 0.001. In the case of the rs2740574 variant in the CYP3A4 gene, patients with normal genotype (TT) presented median = 1.4 µmol/l, (Q25 0.7-Q75 2.7), while patients with the CC + TC genotype had higher levels of ifosfamide (median = 2.0 µmol/l, Q25 1.0-Q75 4.3), p = 0.024. In addition, patients with CC + CT genotype of this variant had a higher risk of non-response to treatment compared to patients with TT genotype (RR = 1.3, 95% CI: 1.07-1.59, p = 0.03). CONCLUSIONS: Polymorphisms in CYP2C9 and CYP3A4 genes are associated with high levels of ifosfamide. In addition, the polymorphism rs2740574 in CYP3A4 was associated with a worse therapeutic response.
RESUMO
Laboratory services for the detection of tuberculosis form an essential component of the DOTS strategy. Our objective was to evaluate the recovery rate and mean time to detection (TTD) of mycobacteria of 2 culture media: the VersaTREK system and the Löwenstein-Jensen medium (LJ). Clinical specimens were processed using the standard N-acetyl-L-cysteine (NALC)-NaOH method, and then inoculated onto VersaTREK system and LJ slants. Of 1510 specimens cultured, a total of 200 mycobacterial isolates (159 Mycobacterium tuberculosis and 41 no M. tuberculosis mycobacteria) were detected. The recovery rates were 84.8% (168/198) for the VersaTREK system and 89.4% (168/188) for LJ (p=0.2); while the contamination rates were 4.2% for the VersaSATREK system and 7.4% for LJ (p<0.001). The TTDs for mycobacteria spp. were 18.2 (+/-11.4) d for the VersaTREK system and 27.9 (+/-10.9) d for LJ (p<0.001). The TTDs for M. tuberculosis were 19.8 (+/-11.2) d for the VersaTREK system and 27.3 (+/-10.2) d for LJ (p<0.001). The difference in TTD between smear-positive and smear-negative specimens for Mycobacterium spp. was 15.9 (+/-10.0) vs 23.0 (+/-12.5) d, and for M. tuberculosis 16.7 (+/-9.5) vs 28.4 (+/-11.1) d for the VersaTREK system. The VersaTREK system significantly reduces the TTDs of mycobacteria detection, which is clinically relevant.