Interacciones relevantes del jugo de pomelo con fármacos. Revisión bibliográfica y soporte para conductas clínicas / Relevant grapefruit juice interactions with drugs. Literature review and support for clinical behaviours

Las interacciones fármaco-nutriente (F-N) tienen el potencial de alterar significativamente la eficacia y seguridad de las terapias farmacológicas. Esta revisión se enfoca en las interacciones del jugo de pomelo con fármacos selectos. Los mecanismos involucrados incluyen la inhibición del sistema metabolizador microsomal CYP3A y del transportador glicoproteína P en el enterocito. El conocimiento y la evitación de estas interacciones clínicamente relevantes aumentarán la seguridad del paciente

Interactions between drugs and nutrients (F-N) have the potential to significantly alter the efficacy and safety of pharmacological therapies. This review focuses on the interactions between grapefruit juice and selected drugs. Involved mechanisms include the inhibition of both CYP 3A4 microsomal metabolizing enzymes and P glycoprotein transporter within the enterocyte. Knowledge (and avoidance) of this clinically relevant interactions will enhance patient safety

Visceral Kaposi's sarcoma remission after intestinal transplant. First case report and systematic literature review.

BACKGROUND: Kaposi's sarcoma (KS) is an infrequent vascular neoplasm commonly diagnosed as an isolated cutaneous lesion that can involve other organs. So far, there are no data in the literature about the development of KS after intestinal transplant. METHODS: In this study, the authors describe a case of "visceral KS" with pulmonary and intestinal involvement and perform a systematic literature review of case reports and single-center series identified in MEDLINE. RESULTS: This case was a 42-year-old man, diagnosed with visceral KS 9 months after receiving an isolated intestinal transplant. He was successfully treated with a combination of sirolimus and liposomal doxorubicin and achieved an 18-month disease-free survival. A total of 54 cases from 27 manuscripts and the present case were analyzed in this study. The mean time from transplant to diagnosis was 17.2 months. Lungs and gastrointestinal tract were the main organs involved. Immunosuppressants were discontinued in two of the three (66.7%) cases, and sirolimus was added in eight cases. Doxorubicin was used in 12 cases. In a univariate analysis, the use of Tacrolimus, type of transplant, and presence of cutaneous KS seem to be the significant predictors of response to therapy and survival; the addition of doxorubicin showed a reduction in graft loss. CONCLUSIONS: Treatment of KS in posttransplant patients should be designed aiming to obtain a complete response, irrespective of the organ affected. Only recipients who are able to achieve a sustained response would be able to obtain long-term disease-free survival.

[A prevalent genetic variety of UDP-glycuronosyl transferase predicts high risk of irinotecan toxicity]. / Una variedad genetica de la UDP- glucuronosil transferasa asociada a toxicidad gastrointestinal por irinotecan.

The advances in genetics and molecular biology have raised new areas in medicine, such as pharmacogenomics, which tries to predict drug responses and toxicities based on the individual genetic variability, describing the so called: pharmacogenomic syndromes. Oncology would find this development extremely useful because of the severe toxicity of chemotherapy. There are a lot of genetic loci under investigation for their potential in predicting drug toxicity, but only three of them have showed clinical usefulness up to now. In particular, quantification of the number of thymine-adenine (TA) dinucleotics in the promoter region of the UDP-glucuronosyl-transferase 1A1 enzime (TA indel) proved to be capable of predicting severe neutropenia in patients exposed to intermediate or high doses of irinotecan. Herein we report a case of a patient with small cell lung cancer who suffered severe hematological and gastrointestinal toxicity after being treated with relatively low doses (65 mg/m(2)) of irinotecan and whose leucocyte DNA analysis showed the presence of seven TA repetitions in both alleles. This case is an example of the clinical applicability and the utility of the test as a toxicity predictor. We also discuss the clinical decisions that may be taken with these patients.

Una variedad genética de la UDP-glucuronosil transferasa asociada a toxicidad gastrointestinal por irinotecan / A prevalent genetic variety of UDP-glycuronosyl transferase predicts high risk of irinotecan toxicity

Los avances en genética y biología molecular han impulsado la aparición de nuevas áreas de estudio en la medicina, como la farmacogenómica, la cual intenta predecir la respuesta y toxicidad a drogas en función de la variabilidad genética de cada individuo, constituyendo los llamados síndromes fármacogenómicos. La oncología podría beneficiarse debido a la gran toxicidad de sus fármacos. Hay varios loci genéticos que se están analizando por su potencial valor predictivo y hasta ahora sólo tres de ellos demostraron cierto grado de utilidad clínica. En especial, el estudio del número de repeticiones del dinucleótido timina-adenina (TA) en el promotor de la enzima UDP-glucuronosil-transferasa (UGT) mostró ser capaz de predecir neutropenia severa en pacientes expuestos a dosis intermedias y altas de irinotecan. Comunicamos el caso de una paciente con cáncer de pulmón de células pequeñas que padeció toxicidad hematológica y gastrointestinal grave tras haber sido tratada con dosis relativamente bajas (65 mg/m2) de irinotecan, y en quien un análisis del ADN leucocitario mostró la presencia de homocigosis para siete repeticiones de TA. Este caso es un ejemplo de aplicabilidad clínica del test, se discute su utilidad como predictor de toxicidad y la conducta a tomar frente a pacientes con estas características.

The advances in genetics and molecular biology have raised new areas in medicine, such as pharmacogenomics, which tries to predict drug responses and toxicities based on the individual genetic variability, describing the so called: pharmacogenomic syndromes. Oncology would find this development extremely useful because of the severe toxicity of chemotherapy. There are a lot of genetic loci under investigation for their potential in predicting drug toxicity, but only three of them have showed clinical usefulness up to now. In particular, quantification of the number of thymine-adenine (TA) dinucleotics in the promoter region of the UDP-glucuronosyl-transferase 1A1 enzime (TA indel) proved to be capable of predicting severe neutropenia in patients exposed to intermediate or high doses of irinotecan. Herein we report a case of a patient with small cell lung cancer who suffered severe hematological and gastrointestinal toxicity after being treated with relatively low doses (65 mg/m2) of irinotecan and whose leucocyte DNA analysis showed the presence of seven TA repetitions in both alleles. This case is an example of the clinical applicability and the utility of the test as a toxicity predictor. We also discuss the clinical decisions that may be taken with these patients.

Una variedad genética de la UDP-glucuronosil transferasa asociada a toxicidad gastrointestinal por irinotecan / A prevalent genetic variety of UDP-glycuronosyl transferase predicts high risk of irinotecan toxicity

Los avances en genética y biología molecular han impulsado la aparición de nuevas áreas de estudio en la medicina, como la farmacogenómica, la cual intenta predecir la respuesta y toxicidad a drogas en función de la variabilidad genética de cada individuo, constituyendo los llamados síndromes fármacogenómicos. La oncología podría beneficiarse debido a la gran toxicidad de sus fármacos. Hay varios loci genéticos que se están analizando por su potencial valor predictivo y hasta ahora sólo tres de ellos demostraron cierto grado de utilidad clínica. En especial, el estudio del número de repeticiones del dinucleótido timina-adenina (TA) en el promotor de la enzima UDP-glucuronosil-transferasa (UGT) mostró ser capaz de predecir neutropenia severa en pacientes expuestos a dosis intermedias y altas de irinotecan. Comunicamos el caso de una paciente con cáncer de pulmón de células pequeñas que padeció toxicidad hematológica y gastrointestinal grave tras haber sido tratada con dosis relativamente bajas (65 mg/m2) de irinotecan, y en quien un análisis del ADN leucocitario mostró la presencia de homocigosis para siete repeticiones de TA. Este caso es un ejemplo de aplicabilidad clínica del test, se discute su utilidad como predictor de toxicidad y la conducta a tomar frente a pacientes con estas características.(AU)

The advances in genetics and molecular biology have raised new areas in medicine, such as pharmacogenomics, which tries to predict drug responses and toxicities based on the individual genetic variability, describing the so called: pharmacogenomic syndromes. Oncology would find this development extremely useful because of the severe toxicity of chemotherapy. There are a lot of genetic loci under investigation for their potential in predicting drug toxicity, but only three of them have showed clinical usefulness up to now. In particular, quantification of the number of thymine-adenine (TA) dinucleotics in the promoter region of the UDP-glucuronosyl-transferase 1A1 enzime (TA indel) proved to be capable of predicting severe neutropenia in patients exposed to intermediate or high doses of irinotecan. Herein we report a case of a patient with small cell lung cancer who suffered severe hematological and gastrointestinal toxicity after being treated with relatively low doses (65 mg/m2) of irinotecan and whose leucocyte DNA analysis showed the presence of seven TA repetitions in both alleles. This case is an example of the clinical applicability and the utility of the test as a toxicity predictor. We also discuss the clinical decisions that may be taken with these patients. (AU)