Effects of serum concentrations of disopyramide and its metabolite mono-N-dealkyldisopyramide on the anticholinergic side effects associated with disopyramide.
The aim of this study was to evaluate the relationship between the anticholinergic side effects associated with disopyramide (DP) and serum DP or mono-N-dealkyldisopyramide (MND) concentrations and the safety range of DP or MND for prevention of anticholinergic side effects in 141 inpatients. The serum DP and MND concentrations were determined by high-performance liquid chromatography. No correlation was observed between creatinine clearance (Ccr) and the ratio of the serum concentration to the dose (C/D) of DP, but a significant inverse correlation was observed between Ccr and the C/D of MND. It was observed that the ratio of MND concentration to DP concentration in the group, whose Ccr was below 20 ml/min, was higher than that of the other groups. Although no significant difference was observed in the DP concentration between the patients without (Group 1) or with (Group 2) anticholinergic side effects, significant differences were observed in the MND concentration, Ccr, and the ratio of MND/DP. The DP concentrations of both Groups 1 and 2 were distributed from 0.13 to about 5 microg/ml. On the other hand, although the MND concentrations of Group 1 were below about 1 microg/ml, the MND concentrations of Group 2 were above about 1 microg/ml. These results suggest that not only DP concentration but also MND concentration should be monitored in patients whose renal function is decreased to prevent anticholinergic side effects associated with DP, and that when serum MND concentration was over approximately 1 microg/ml, the dose should be decreased or discontinued.
Tsuchishita
Yoshimasa
Y
Department of Pharmacy, Maizuru Kyosai Hospital, Federation of National Public Services and Affiliated Mutual Associations, Kyoto, Japan.
Fukumoto
Kyoko
K
Kusumoto
Masaaki
M
Ueno
Kazuyuki
K
D000328:Adult; D000368:Aged; D000889:Anti-Arrhythmia Agents / Q000009:adverse effects* / Q000097:blood* / Q000493:pharmacokinetics; D001342:Autonomic Nervous System Diseases / Q000139:chemically induced*; D002851:Chromatography, High Pressure Liquid; D003404:Creatinine / Q000097:blood; D004206:Disopyramide / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D014555:Urination Disorders / Q000139:chemically induced; D014987:Xerostomia / Q000139:chemically induced
D000889:Anti-Arrhythmia Agents; C030438:4-(isopropylamino)-2-(2-pyridyl)-2-phenylbutyramide; D003404:Creatinine; D004206:Disopyramide