Pharmacokinetic study of aprindine and moxaprindine in dogs

Moxaprindine and aprindine were each administered to a group of six dogs at a single dose of 5.5 mg/kg by intravenous injection and at the same dose 14 days later by oral route. In each series the sequence of route of administration was randomized. In a second experiment, 8 to 12 weeks later, the dogs were treated for 5 successive days with the same drug at the dose of 5.5 mg/kg twice daily. Moxaprindine and aprindine are similar in several of their pharmacokinetic characteristics. Their plasma levels are suitably explained by a two-compartment open model. No significant differences are found between their respective terminal plasma half-lives nor their k12, k21 and kel values; on multiple dosing, the steady state is reached within 3 days with both drugs. However, the plasma levels of moxaprindine are twice as high as those of aprindine. Consequently the distribution volume of moxaprindine is half as small as that of aprindine. Moxaprindine is 95.3% protein bound at 1 microgram/ml and 93.6% at 2 microgram/ml; the corresponding values for aprindine are 98.3% and 98.1%. These differences may be of clinical significance as regards therapeutic effectiveness and safety of these two substances.