Verapamil

pharmacological · nervous · cardiovascular · digestive · Oral · IV

Verapamil. Non-dihydropyridine CCB — strongest cardiac (AV-nodal) effect of the class. Used for AF rate control, certain SVTs, hypertension, and… Oral half-life 5.4 h.

Non-dihydropyridine CCB — strongest cardiac (AV-nodal) effect of the class. Used for AF rate control, certain SVTs, hypertension, and migraine prophylaxis. Strong CYP3A4 + P-glycoprotein inhibitor → major DDI source. Constipation (~25%).

PK: the oral half-life of 5 h is a TMAX COLLISION — its paper states "time to peak plasma concentrations of 4.91+/-0.89h" — and that paper actual oral half-life is 55.1 h, because THE CITED STUDY USED A RETARD FORMULATION on a route the registry lists as plain oral. Its input is time-varying and INCOMPLETE at 39.17% cumulative, so no first-order rate can represent it, and ka 0.5 is dropped. The route split is resolved by a same-subject two-route study: 4.03 to 5.38 h for the two enantiomers "following oral administration ... were similar to those previously obtained following intravenous administration". V 130 L was an unsourced back-calculation two to three times too small; the measured range is 270 to 460 L and the lower endpoint is stored. THE MOST IMPORTANT FINDING IS NOT A NUMBER: first-pass is STEREOSELECTIVE, giving a (+)/(-) plasma ratio of 4.92 orally against about 2 intravenously, while the (-) enantiomer is 8 to 10 times more potent on conduction — so "the serum concentration-response curve after oral application is displaced towards the right reflecting lower potency". The SAME total concentration is two to three times less potent orally, which no effect compartment can fix. Two references are victim-drug studies with no verapamil kinetics. INTERACTIONS: TWO OF THREE INVERT THROUGH 0.5 µM, the same constant its sibling diltiazem fails to share. The simvastatin edge does not fit and is left alone. NOTE THE BUSPIRONE SOURCE REPORTS BOTH CALCIUM BLOCKERS IN ONE SENTENCE — "Verapamil and diltiazem increased the ... AUC (0-infinity) 3.4-fold" — the shared-sentence shape that has produced transplants elsewhere in this catalogue; here both records correctly store the same ratio, because the sentence genuinely reports one figure for both drugs.

Pharmacokinetics

Related compounds

Sources: PMID:6508982, PMID:7202473, PMID:971476