PHOSPHATIDYLCHOLINE - A PHARMACOLOGICALLY RELEVANT SITE FOR BINDING OF ANTIARRHYTHMICS

Binding of antiarrhythmics to phosphatidylcholine (PC) has been quantified by measuring the drug-induced fluorescence increase in 8-anilino-1-naphthalene-sulfonate (ANS)-treated PC membranes: (1) The ability of test compounds to increase fluorescence intensity to 50% varies between 1.3 and 88 × 10-6 M, exhibiting a potency ratio of 1.8 log units; (2) Antiarrhythmics exhibit extreme variations in lipophilicity. Depending on the methodological approach applied, lipophilicity ranges of 4-5.5 log units between the most lipophilic compound asocainol and the most hydrophilic compound procainamide are observed; (3) Binding of antiarrhythmics to PC membranes is mainly determined by drug lipophilicity; and (4) Binding of a variety of antiarrhythmics to PC appears to correlate significantly with the mean daily dosage (n = 8; r = 0.97) as well as the therapeutic plasma concentration (n = 9; r = 0.90) of these drugs. © 1990.