個別薬物療法のための血漿中蛋自非結合型Disopyramide濃度測定の有用性

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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 0.8 μg/mL in the effective group, whereas it was lower than 0.8 μg/ 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 0.1-1.0 μg/mL, and no patient developed side effects such as tachycardia or constipation due to the anticholinergic effect. In conclusion, an unbound concentration of DP in plasma of over 0.8 μg/mL can be used as an index of the effectiveness of anti-arrhythmic therapy in therapeutic drug monitoring.
日本臨床薬理学会の論文
2003-01-31

個別薬物療法のための血漿中蛋自非結合型Disopyramide濃度測定の有用性

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