ABSTRACT
Objective To provide a reference for the individualized medication of tacrolimus in children after living related liver transplantation,according to the effect of CYP3A5 genotyping on the concentration/dose ratio of tacrolimus in children with living related liver transplantation.Methods Peripheral blood samples were collected from children with living related liver transplantation in the transplant center.The CYP3A5 genotype was determined by polymerase chain reaction (PCR)pyrosequencing.Related indicators such as tacrolimus dose and concentration in children with living related liver transplantation were collected within 3 months after operation.According to the donor/receptor genotype,the donor/receptor expression group,the donor/receptor single expression group,and the donor/receptor non-expression group were set up.Tacrolimus concentration/dose (C0/D) ratio was statistically analyzed at 5th day,7th day,14th day,28th day,2nd month and 3rd month after administration.Results Among the 76 patients,there were 21 patients (27.63％) in CYP3A5 donor/receptor non-expression group,27 patients (35.53％) in donor/receptor single expression group,and 28 patients (36.84％) in the donor/receptor expression group.The time to the target concentration range (C0＞8 ng/mL) in CYP3A5 donor/receptor expression group was longer than in donor/receptor single expression group and donor/receptor non-expression group.Except for the individual time points,there were significant differences between CYP3A5 donor/receptor expression group and donor/receptor non expression group,or between donor/receptor non-expression group and donor/receptor single expression group,or between donor/receptor expression group and donor/receptor single expression group at rest time points (P＜0.05 for all).Conclusion In the CYP3A5 donor/receptor gene expression group,the higher dose was needed to reach the target concentration range than the gene single expression group and the donor/receptor non-expression group.Except for individual time points,there were significant differences in C0/D at rest different time points.Regardless of whether the donor or recipient contained the CYP3A5* 1 allele,C0/D was lower than the non-expressed type of the gene.Considering the polymorphism of the donor/receptor CYP3A5 gene,it was worthful for children with living related liver transplantation to allow the drug concentration to reach the therapeutic window as soon as possible and reduce organ rejection and adverse reactions.
ABSTRACT
Objetivo: Determinar los niveles/dosis (ND) del ácido valproico y la influencia de los fármacos inductores y no inductores enzimáticos en pacientes voluntarios de la ciudad de Mérida-Venezuela. Materiales y métodos: Se realizó un estudio experimental, observacional, prospectivo de corte transversal, en el Hospital de Mérida-Venezuela. Luego de pasar por los criterios de inclusión y exclusión, los pacientes firmaron el consentimiento informado en forma individual y voluntaria.El protocolo consistió en obtener la sangre de 88 pacientes (42 hombres y 46 mujeres) con edades entre 16 y 68 años, que sufrían de convulsiones parciales o generalizadas y que estaban recibiendo 3,97-38,04 mg/kg de ácido valproico (AVP) dos veces al día en monoterapia o en combinación con carbamacepina (CBZ), fenobarbital (PB), fenitoína (PHT), lamotrigina (LTG) y oxcarbacepina (OXC). Se tomó la muestra después de cuatro semanas de tratamiento, en condiciones de ayuno y antes de la administración del medicamento del presente día, para determinar posteriormente la concentración plasmática por medio del método de radioinmunoensayo. Con los datos de la concentración plasmática se determinó el ND. Resultados: En monoterapia con AVP se encontró que la concentración plasmática media era de 64,94 mg/l (DE 31,7) y el ND de 4,32 (DE 2,1). En combinación de AVP+CBZ+PB se obtuvo un ND de 2,31 (DE 0,06), con la combinación AVP+PB+PHT se obtuvo el ND de 2,46 (DE 0,43) y con la combinación AVP+PB+OXC se obtuvo un ND de 4,63 (DE 3,12). Conclusiones: Los fármacos administrados en forma concomitante influyen sobre la concentración plasmática y el ND del AVP en un grupo de pacientes de Mérida-Venezuela.
Objective: To determine valproic acid level/dose ratio (ND) and the influence of enzyme-inducing and non-enzymeinducing drugs in volunteer patients of the city of Mérida, Venezuela. Materials and methods: An experimental, observational, prospective, cross-sectional study was conducted at the Hospital de Mérida, Venezuela. After undergoing the inclusion and exclusion criteria process, patients signed an informed consent individually and voluntarily. The protocol consisted in collecting blood from 88 patients (42 males y 46 females) from 16 to 68 years old, who had partial or generalized seizures, and were receiving 3.97-38.04 mg/kg of valproic acid (AVP) twice a day as monotherapy or combination therapy with carbamazepine (CBZ), phenobarbital (PB), phenytoin (PHT), lamotrigine (LTG) and oxcarbazepine (OXC). A sample was taken after four weeks of treatment, in the fasting state and before the administration of the medication of the day. Afterwards, plasma concentration was determined through a radioimmunoassay method. The ND was established using the plasma concentration data. Results: AVP monotherapy showed a mean plasma concentration of 64.94 mg/l (SD 31.7) and ND of 4.32 (SD 2.1). Combination therapy with AVP+CBZ+PB showed an ND of 2.31 (SD 0.06), combination therapy with AVP+PB+PHT showed an ND of 2.46 (SD 0.43) and combination therapy with AVP+PB+OXC showed an ND of 4.63 (SD 3.12). Conclusions: The administration of concomitant drugs affected plasma concentration and AVP ND in a group of patients of the Hospital de Mérida, Venezuela.
ABSTRACT
El objetivo de este estudio fue evaluar los beneficios de la rotación de morfina a metadona oral en pacientes con poca respuesta analgésica o efectos adversos derivados de la morfina. Diecisiete pacientes con cáncer avanzado que recibían morfina por dolor no controlado o efectos adversos severos fueron rotados a metadona cada ocho o doce horas, según un esquema de rotación rápida utilizando diferentes dosis ratios. La intensidad del dolor y efectos adversos fueron evaluados diariamente y comparados antes y después del cambio. Se documentó la dosis de morfina prerrotación, la dosis media inicial de metadona, dosis al séptimo día así como la dosis media final. Antes de la rotación la dosis media equivalente de morfina oral fue 118.71 mg/día, luego de la misma la dosis media inicial de metadona fue de 17.94 mg/día, al séptimo día fue 27.06 mg/día y la dosis media final de metadona fue 34.12 mg/día. Los motivos de la rotación fueron: dolor no controlado, efectos adversos limitantes o la suma de ambos. Se encontraron mejorías significativas en la analgesia (p<0.05) así como alivio sintomático relevante en los efectos adversos. Se registraron efectos colaterales debidos a la utilización de metadona en ocho pacientes que revirtieron con el tratamiento sintomático. La metadona demostró ser una opción terapéutica válida para el grupo de pacientes estudiados. Se recomienda precaución en la rotación a metadona en pacientes tolerantes a altas dosis de opioides.
The aim of this study was to evidence the clinical benefits of switching from morphine to oral methadone in patients who experience poor analgesia or adverse effects from morphine. Seventeen advanced cancer patients receiving morphine but with uncontrolled pain or severe opioid adverse effects were switched to oral methadone administered every 8 or 12 hours according to a scheme of rapid switching using different dose ratios.Intensity of pain and adverse effects were assessed daily and compared before and after switching. Pre switching doses of morphine, initial, day 7 and final methadone doses were recorded. Before the switch, the median equivalent daily dose of morphine was 118.71 mg/day; after the switch the initial dose of methadone (median) was 17.94 mg/day, 27.06 mg/day at day 7 and the final dose of methadone (median) was 34.12 mg/day. The reasons for switching were: uncontrolled pain, adverse effects or both. Significant improvements in pain (p<0.05) and relevant changes in adverse effects were reported. Methadone - related side effects reported in 8 patients were relieved after treatment. In patients with cancer pain and/or adverse effects of oral methadone is a valid therapeutic option.Caution is recommended when switching from any opioid to methadone, in patients who are tolerant to high doses of opioids.
O objetivo deste estudo foi avaliar os benefícios da passagem de morfina a metadona oral em pacientes com pouca resposta analgésica o efeitos adversos derivados da morfina. Dezessete pacientes com câncer avançado que recebiam morfina por dor não controlada o efeitos adversos severos foram medicados com metadona cada 8 ou 12 horas, adotando um esquema de conversão rápida utilizando diferentes doses-ratios. A intensidade da dor e efeitos adversos foi avaliada diariamente e comparados antes e depois da troca. Foi documentado a doses de morfina pré-conversão, a doses media inicial de metadona, a dosagem ao dia 7, como também a doses media final. Antes da troca a doses media equivalente de morfina oral foi de 118.71 mg/dia, logo após as doses media inicial de metadona foi de 17.94 mg/dia, ao dia 7 foi de 27.06 mg/dia e a doses final de metadona foi 34.12 mg/dia. O motivo da passagem a metadona foi: dor não controlada, efeitos adversos limitantes o a soma deles. Foram encontradas melhorias significativas na analgesia (p<0.05) alem do alivio relevante dos efeitos adversos. Se registraram efeitos colaterais pela utilização da metadona em 8 pacientes que melhoraram com o tratamento sintomático. A metadona demonstrou ser uma opção terapêutica valida para o grupo de pacientes estudados. Recomendamos cuidados na passagem a metadona em pacientes tolerantes a altas doses de opioides.