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Background: Abiraterone acetate was approved by FDA and EMA in April and September 2011, respectively for treatment of patients with casteration resistant prostate cancer and those previously treated with docetaxel. It is a selective inhibitor of androgen biosynthesis which potentially and irreversibly blocks CYP17, a crucial enzyme in oestrogen and testosterone synthesis. Materials and Methods: This retrospective study was conducted to evaluate the safety and efficacy of abiraterone acetate in the treatment of castration resistant prostate cancer patients. Twenty-two male patients diagnosed with CRPC and experienced treatment failure with one or more lines of treatment (hormonal manipulation or chemotherapy) were selected and administered abiraterone acetate (1,000 mg daily) along with prednisone (5 mg twice daily). Results: Out of 22 patients, 32% had a good response in reduction of PSA values, while 22% had progression in disease and 45% had a stable disease. Potassium, Haemoglobin, and serum sreatinine levels were not affected by the drug. Due to severe GI intolerance, the drug had to be stopped for one patient. The results of this study showed that abiraterone acetate significantly lowered the PSA values and prolonged progression- free survival in metastatic castration resistant prostate cancer patients who had progressed after first-line or second-line treatment. The overall average median survival and the median duration of drug exposure for CRPC who received AA was found to be 11.1 months [range 3-18]. Since AA plus prednisolone are available as oral dosage forms, they can be given in outpatient setting. Conclusion: Abiraterone acetate is a drug of choice for CRPC and also for those who had previously received one or two chemotherapy regimens. Since it is a new therapeutic regimen, this study included small sample size, but there are a few studies indicating the therapeutic efficacy of AA among patients with castration-resistant prostate cancer.
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AIM: Adverse drug reactions to 5-Fluorouracil(5-FU) is frequent and largely attributable to genetic variations in the DPYD gene, a rate limiting enzyme that clears 5-FU. The study aims at understanding the pharmacogenetic landscape of DPYD variants in south Asian populations. MATERIALS & METHODS: Systematic analysis of population scale genome wide datasets of over 3000 south Asians was performed. Independent evaluation was performed in a small cohort of patients. RESULTS: Our analysis revealed significant differences in the the allelic distribution of variants in different ethnicities. CONCLUSIONS: This is the first and largest genetic map the DPYD variants associated with adverse drug reaction to 5-FU in south Asian population. Our study highlights ethnic differences in allelic frequencies.
Asunto(s)
Antimetabolitos Antineoplásicos/toxicidad , Dihidrouracilo Deshidrogenasa (NADP)/genética , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/genética , Fluorouracilo/toxicidad , Farmacogenética , Polimorfismo de Nucleótido Simple , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Pueblo Asiatico/genética , Estudios de Cohortes , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/enzimología , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/etiología , Femenino , Frecuencia de los Genes , Humanos , Masculino , Persona de Mediana Edad , Población Blanca/genética , Adulto JovenRESUMEN
CONTEXT: Citicoline (CN) and piracetam (PM) combination in tablet formulation is newly introduced in market. It is necessary to develop suitable quality control methods for rapid and accurate determination of these drugs. AIM: The study aimed to develop the methods for simultaneous determination of CN and PM in combined dosage form. MATERIALS AND METHODS: The first method was developed by formation and solving simultaneous equations using 280.3 and 264.1 nm as two analytical wavelengths. Second method was absorbance ratio in which wavelengths selected were 256.6 nm as its absorptive point and 280.3 nm as λmax of CN. According to International Conference on Harmonization (ICH) norm, the parameters - linearity, precision, and accuracy were studied. The methods were validated statistically and by recovery studies. RESULTS: Both the drugs obeyed Beer-Lambert's law at the selected wavelengths in concentration range of 5-13 µg/ml for CN and 10-22 µg/ml for PM. The percentage of CN and PM in marketed tablet formulation was found to be 99.006 ± 0.173 and 99.257 ± 0.613, respectively; by simultaneous equation method. For Q-Absorption ratio method the percentage of CN and PM was found to be 99.078 ± 0.158 and 99.708 ± 0.838, respectively. CONCLUSIONS: The proposed methods were simple, reproducible, precise and robust. The methods can be successfully applied for routine analysis of tablets.