Subject(s)
Angiofibroma/drug therapy , Facial Neoplasms/drug therapy , Immunosuppressive Agents/therapeutic use , Sirolimus/therapeutic use , Administration, Topical , Chemistry, Pharmaceutical , Child, Preschool , Female , Humans , Immunosuppressive Agents/administration & dosage , Male , Sirolimus/administration & dosage , Tuberous Sclerosis/complicationsABSTRACT
Objetivo Evaluar la efectividad y seguridad del tratamiento con 5-azacitidina en síndrome mielodisplásico. Métodos Revisión de historias clínicas de pacientes que recibieron 5-azacitidina 75mg/m2 subcutánea durante 7 días, cada 28 días en 12 ciclos. Se valoró la respuesta objetiva, mejoría clínica y tiempo hasta la progresión de la enfermedad. Se recogieron las reacciones adversas descritas en la historia clínica. Resultados Seis pacientes fueron candidatos a tratamiento con 5-azacitidina. Tres casos fueron evaluables tras el período considerado. La mayoría permanecieron en respuesta parcial o mejor al finalizar el estudio, dejando de precisar transfusiones. En una paciente se retrasó la progresión a leucemia.Conclusiones5-Azacitidina podría considerarse un fármaco relativamente efectivo y seguro, pudiendo haber contribuido al control de citopenias periféricas, a mejorar la calidad de vida y a retrasar la progresión a leucemia. Serían necesarios estudios con mayor número de pacientes que corroborasen estos resultados (AU)
Objective To assess the effectiveness and safety of using 5-azacitidine to treat myelodysplastic syndromes. Methods Review of medical records of patients who received 5-azacitidine 75mg/m2 subcutaneously for during 7 days every 28 days in twelve cycles as compassionate use. We evaluated the objective response, clinical improvement and time to disease progression. We recorded adverse reactions described in the medical history. Results Six patients were candidates for treatment with 5-azacitidine. Three cases were evaluated over the study period. Most remained in partial response or better after the study, and no longer needed transfusions. In one patient, the treatment appeared to delay progression to leukaemia.Conclusions5-Azacitidine might be considered an effective and relatively safe drug, and may have contributed to controlling peripheral cytopenias, improving the quality of life and delaying progression to leukaemia. Additional studies with more patients are needed to support these results (AU)
Subject(s)
Humans , Male , Female , Middle Aged , Aged , Antimetabolites/therapeutic use , Azacitidine/therapeutic use , Myelodysplastic Syndromes , Anemia, Refractory, with Excess of Blasts/drug therapy , Anemia, Refractory, with Excess of Blasts/therapy , Combined Modality Therapy , Disease Progression , Drug Eruptions , Drug Evaluation , Medical Records , Platelet Transfusion , Quality of Life , Recombinant Proteins , Retrospective StudiesABSTRACT
OBJECTIVE: To assess the effectiveness and safety of using 5-azacitidine to treat myelodysplastic syndromes. METHODS: Review of medical records of patients who received 5-azacitidine 75mg/m(2) subcutaneously for during 7 days every 28 days in twelve cycles as compassionate use. We evaluated the objective response, clinical improvement and time to disease progression. We recorded adverse reactions described in the medical history. RESULTS: Six patients were candidates for treatment with 5-azacitidine. Three cases were evaluated over the study period. Most remained in partial response or better after the study, and no longer needed transfusions. In one patient, the treatment appeared to delay progression to leukaemia. CONCLUSIONS: 5-Azacitidine might be considered an effective and relatively safe drug, and may have contributed to controlling peripheral cytopenias, improving the quality of life and delaying progression to leukaemia. Additional studies with more patients are needed to support these results.
Subject(s)
Antimetabolites/therapeutic use , Azacitidine/therapeutic use , Myelodysplastic Syndromes/drug therapy , Aged , Anemia, Refractory, with Excess of Blasts/drug therapy , Anemia, Refractory, with Excess of Blasts/therapy , Antimetabolites/adverse effects , Azacitidine/adverse effects , Combined Modality Therapy , Compassionate Use Trials , Diarrhea/chemically induced , Disease Progression , Drug Eruptions/etiology , Drug Evaluation , Female , Filgrastim , Granulocyte Colony-Stimulating Factor/therapeutic use , Humans , Male , Medical Records , Middle Aged , Platelet Transfusion , Quality of Life , Recombinant Proteins , Retrospective StudiesABSTRACT
OBJECTIVE: To determine how single nucleotide polymorphisms located on genes MDR1, CYP3A4 and CYP3A5 affect the absorption kinetics of cyclosporine in cardiac transplant patients. METHOD: We selected a sample of 30 adult patients having previously undergone a primary cardiac transplant and who had received cyclosporine as an immunosuppressant. During the first month after the transplant, we performed a pharmacokinetic study of each patient to determine values in the cyclosporine concentration area under the 12-hour curve, steady-state cyclosporine concentration, maximum cyclosporine concentration, and time to reach that concentration. Single nucleotide polymorphisms were genotyped in all patients: MDR1 3435C > T, CYP3A4-390A > G and CYP3A5 6986A > G. RESULTS: Being a carrier of the T-allele for polymorphism MDR1 3435C > T is associated with higher values in the cyclosporine concentration area under the 12-hour curve (p = 0.01) and in steady-state cyclosporine concentration (p = 0.05), compared with those from patients who do not carry that allele. DISCUSSION: Our results show that genotype differences in MDR1 3435C > T can explain part of the variability in cyclosporine absorption among individuals in the population of Spanish cardiac transplant recipients.
Subject(s)
ATP Binding Cassette Transporter, Subfamily B, Member 1/genetics , Biotransformation/genetics , Cyclosporine/pharmacokinetics , Cytochrome P-450 CYP3A/genetics , Heart Transplantation , Immunosuppressive Agents/pharmacokinetics , Intestinal Absorption/genetics , Polymorphism, Single Nucleotide , ATP Binding Cassette Transporter, Subfamily B , ATP Binding Cassette Transporter, Subfamily B, Member 1/metabolism , Adolescent , Adult , Aged , Alleles , Area Under Curve , Cyclosporine/blood , Cytochrome P-450 CYP3A/metabolism , Female , Genotype , Humans , Male , Middle Aged , Spain , Young AdultABSTRACT
Objetivo: Determinar el papel de polimorfismos de nucleótido único localizados en los genes MDR1, CYP3A4 y CYP3A5 sobre la cinética de absorción de ciclosporina en pacientes trasplantados cardíacos. Método: Se seleccionó una muestra de 30 pacientes adultos sometidos a un primer trasplante de corazón que habían recibido ciclosporina como tratamiento inmunosupresor. En el primer mes después del trasplante se realizó un estudio farmacocinético a cada paciente para determinar los valores del área de concentración de ciclosporina bajo la curva de 12 h, concentración de ciclosporina en estado de equilibrio, concentración de ciclosporina máxima y el tiempo en alcanzar dicha concentración. En todos los pacientes se genotipificaron los polimorfismos de nucleótido único: MDR1 3435C > T, CYP3A4-390A > G y CYP3A5 6986A > G. Resultados: Ser portador del alelo T para el polimorfismo MDR1 3435C > T se asoció a valores mayores de área de concentración de ciclosporina bajo la curva de 12 h (p = 0,01) y de concentración de ciclosporina en estado de equilibrio (p = 0,05), en comparación con los pacientes no portadores de dicho alelo. Discusión: Nuestros resultados muestran que las diferencias genotípicas de MDR1 3435C > T podrían explicar parte de la variabilidad interindividual en la absorción de la ciclosporina en la población española de trasplantados cardíacos (AU)
Objective: To determine how single nucleotide polymorphisms located on genes MDR1, CYP3A4 and CYP3A5 affect the absorption kinetics of cyclosporine in cardiac transplant patients. Method: We selected a sample of 30 adult patients having previously undergone a primary cardiac transplant and who had received cyclosporine as an immunosuppressant. During the first month after the transplant, we performed a pharmacokinetic study of each patient to determine values in the cyclosporine concentration area under the 12-hour curve, steady-state cyclosporine concentration, maximum cyclosporine concentration, and time to reach that concentration. Single nucleotide polymorphisms were genotyped in all patients: MDR1 3435C > T, CYP3A4-390A > G and CYP3A5 6986A > G. Results: Being a carrier of the T-allele for polymorphism MDR1 3435C > T is associated with higher values in the cyclosporine concentration area under the 12-hour curve (p = 0.01) and in steady-state cyclosporine concentration (p = 0.05), compared with those from patients who do not carry that allele. Discussion: Our results show that genotype differences in MDR1 3435C > T can explain part of the variability in cyclosporine absorption among individuals in the population of Spanish cardiac transplant recipients (AU)
