Pharmacokinetics and Metabolism of Tiapamil

The main pathways of biotransformation of tiapamil and basic pharmacokinetic information on the drug are presented and compared with those of verapamil. Both compounds are metabolized by similar pathways consisting mainly of N- and O-dealkylation. In man, the two main metabolites of tiapamil in blood and urine are the N-desmethyl derivative and the other secondary amine which has lost the dimethoxyphenethyl-moiety. Both metabolites have low pharmacological activity and do not contribute significantly to the effect of the parent drug. Analysis of single intravenous doses of 10 and 50 mg revealed that tiapamil has pharmacokinetic parameters very similar to those of verapamil, the total plasma clearances for both compounds being about 800 ml/min. Due to its somewhat smaller volume of distribution (twice body weight), tiapamil has a slightly shorter half-life of elimination from plasma [t½β] – 2.5 h – than does verapamil (4 h). On oral dosing, however, both drugs have substantially reduced bioavailability of about 20%, this being due to extensive first-pass metabolism rather than to incomplete absorption. Tiapamil plasma levels following intravenous infusion or multiple oral dosing may