The unbound concentration of disopyramide (DP) in plasma was studied to determine whether or not it is a useful index to assess the effectiveness of DP in anti-arrhythmic therapy. In 20 arrhythmic patients administered DP (Rythmodan^®, 100-600 mg/day), there was no correlation between the dose and total or unbound plasma concentration of DP. The values of unbound fraction (fp) of DP in plasma widely varied from 0.25 to 0.57. The fp values were not correlated with the albumin concentration in plasma, but did correlate with the concentration of α₁-acid glycoprotein. We further examined the relationship between the total or unbound plasma concentrations of DP and it's effectiveness in 16 of the 20 patients (4 patients had side effects). There was significant difference in the plasma concentrations of DP between the effective group and the ineffective group.However, as the range of the concentration for the two groups overlapped in 75%. the total concentration cannot be used to define the effectiveness. On the other hand, the unbound concentration of DP was greater than 0.8μg/mL in the effective group, whereas it was lower than 0.8μg/mL in the ineffective group.There was no correlation between the unbound concentration of mono-N-dealkyldisopyramide (MND) and the effectiveness. The range of the unbound plasma concentration of MND was 0.1-1.0μg/mL, and no patient developed side effects such as tachycardia or constipation due to the anticholinergic effect. In conciusion, an unbound concentration of DP in plasma of over 0.8μg/mL can be used as an index of the effectiveness of anti-arrhythmic therapy in therapeutic drug monitoring.

View full abstract

The major problem in the management of information on adverse events is found in both the clinical trial sponsor and the trial institution. The primary cause is inconsistency in the sponsors and trial institutions due to the use of original management methods which differ among sponsors or among trial institutions.
In order to solve this problem, it is proposed to classify adverse events into three groups: “Case Report A”, “Case Report B” and “Accumulated Information” based on the detected place (Japan or foreign country), the detected phase (clinical trial or post-marketing), unknown or known event, and the degree of severity. “Case Report A” and “Case Report B” will be evaluated individually, and “Accumulated Information” will be evaluated collectively in the institutional review board.
Electronic list data is provided to the trial institution as the standard version only, and individual alteration request to the list data from institutions should not be accepted. Therefore, each institution should arrange the list data for creating its own database, if needed. The list data is presently provided by electronic media which are currently used widely such as the floppy disk or CD-R etc, but it might be necessary to plan for use by electronic mail.
By classifying the adverse events and using electronic data for providing information about adverse events, more efficient information management is expected in both sponsors and trial institutions.

View full abstract