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Owing to their narrow therapeutic range, most antiarrhythmic agents require Therapeutic Drug Monitoring (TDM). Though TDM is an effective tool for adjusting the individual dosage to the optimum level, no study has shown that TDM is useful for dose adjustment in the case of cibenzoline. The aim of this study was thus to evaluate the usefulness of TDM in cibenzoline therapy.In the National Cardiovascular Center, TDM was introduced for cibenzoline in 1998. This resulted in reductions in mean serum concentrations and mean doses, and very few adverse effects have been reported. Thanks to dosage adjustment based on TDM, there was a decrease in the proportion of patients having serum concentrations of above 400 ng/mL from 2000 onwards. These results suggest that TDM is an effective tool for preventing cibenzoline toxicity and that it helps to ensure that cibenzoline is administered properly.

Unsubstituted and trimethyl-4,8-diphosphathiophenetriptycenes (4 and 3d) were synthesized by reduction of the corresponding phosphine oxides (8a and 8b) with trichlorosilane which were prepared by the reaction of trilithium salts, derived from tri-3-thienylphosphine oxides (7a and 7b), with P(OPh)3. The reaction of 3d with W(CO)5(THF) gave a 1:2 complex 12 in high yield.