Disopyramide concentrations in human plasma and saliva: comparison of disopyramide concentrations in saliva and plasma unbound concentrations.
OBJECTIVE
This study was performed to investigate whether it is possible to use saliva instead of blood usually used for therapeutic drug monitoring (TDM) of disopyramide.


METHODS
Six healthy male volunteers ingested 200 mg of disopyramide base, and the disopyramide concentrations in saliva and plasma (total and unbound) were determined by the HPLC.


RESULTS
Disopyramide concentration-time profiles for the saliva were nearly equal to those for the plasma unbound concentrations. A large variation for absorption time of the drug was observed among the subjects. Disopyramide concentrations (Cs) in saliva did not correlated well with plasma total concentrations (Cp), r = 0.799, but did well with unbound concentrations (Cpu), r = 0.969, for the 3-12 h period on the elimination phase. The mean ratio of disopyramide concentrations in the saliva against the plasma unbound concentrations was almost constant (1.02(0.10), CV = 9.7%) for the period. The pharmacokinetic parameters (tmax, t1/2, AUC, AUMC and MRT values) for disopyramide calculated from the saliva data were nearly equal to those from the unbound data.


CONCLUSIONS
Disopyramide concentrations in saliva correlated well with plasma unbound concentrations on the elimination phase.
Sagawa
K
K
Department of Pharmaceutics, Meiji College of Pharmacy, Tokyo, Japan.
Mohri
K
K
Shimada
S
S
Shimizu
M
M
Muramatsu
J
J
D000328:Adult; D000889:Anti-Arrhythmia Agents / Q000097:blood / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D004206:Disopyramide / Q000097:blood / Q000493:pharmacokinetics*; D016903:Drug Monitoring / Q000379:methods*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008297:Male; D012016:Reference Values; D012463:Saliva / Q000378:metabolism*
D000889:Anti-Arrhythmia Agents; D004206:Disopyramide