Practical application of acid dissociation in monitoring patients treated with adalimumab.

Patients treated with adalimumab (ADL) can induce anti-ADL antibodies (AAA) formation that is associated with low drug levels and clinical non-response. But, in the majority of the assays, the measurement of AAA is hampered by the presence of the drug itself. In support of immunogenicity assessment in clinical samples with subtherapeutic ADL levels, we proved acid pre-treatment for AAA detection with the Promonitor-enzyme-linked immunosorbent assay (ELISA). Were measured AAA after acidification in 32 serum samples with a subtherapeutic ADL trough level. ADL and AAA concentrations were measured by ELISA (Promonitor). The impact of drug concentration on AAA recovery (with or without acidification) was also evaluated by mixing known amounts of ADL (0.25, 0.5 and 1 mg/L) and AAA (100, 200, 300 and 400 AU/mL) from clinical samples in pooled serum. The drug significantly inhibited the detection of AAA in untreated samples. And progressively higher levels of ADL cause increasing inhibition of signal. Acid pre-treatment carried a significant increase in assay response, particularly at lower free ADL concentrations. AAA were detected in the 53 % of the samples after acid dissociation. In seven patients, the positive AAA after dissociation was detected in the first monitoring of ADL and five patients were positive 3 months later for AAA with the standard assay. Monitoring AAA using acid dissociation in patients with subtherapeutic circulating level of ADL could detect precocious problems of bioavailability, assess the immunogenicity of ADL and may be used to optimise dose regimens, thereby preventing prolonged use of inadequate therapy and guide change of treatment.

Valor añadido del cálculo del filtrado glomerular mediante MDRD-4 en la estimación del riesgo de sobredosificación digitálica / Added value of glomerular filtration estimation by MDRD-4 in the risk assessment of the digitalic overdose

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Interacción farmacocinética entre fenitoína y buflomedilo / Pharmacokinetic interaction between phenytoin and buflomedil

La prevalencia del tratamiento con fármacos antiepilépticos ha aumentado en pacientes ancianos. Esto unido a la especial fragilidad de estos pacientes, los sitúa entre los grupos farmacológicos que con mayor frecuencia se ven implicados en la aparición de interacciones en este grupo de población. Se describe el caso de una anciana que seguía tratamiento crónico con fenitoína y experimentó una reducción de su concentración plasmática al introducir buflomedilo como parte de su tratamiento. Los pacientes en los que se administren simultáneamente ambos fármacos serían candidatos a una estrecha monitorización con la finalidad de identificar precozmente esta interacción y evitar la posible toxicidad que pudiera derivarse de plantear un aumento de la dosis de fenitoína (AU)

There has been an increase in treatment with antiepileptic drugs in the elderly. This, together with the particular frailty of these patients, places them among the pharmacological groups that have a higher frequency of interactions in this population group. The case is presented of an elderly patient who followed long-term treatment with phenytoin and showed a reduction in her plasma phenytoin levels on introducing buflomedil as part of her treatment. Patients who are given both drugs simultaneously should be subjected to close monitoring, with the aim of identifying this interaction earlier and avoid the possibly toxicity that could arise from deciding to increase the phenytoin dose (AU)