Non-dihydropyridine CCB — Cav1.2 blocker with both vascular and cardiac (AV-nodal) effects. Used for AF rate control + hypertension. Moderate CYP3A4 inhibitor → significant DDI footprint (statin myopathy, raised cyclosporine, raised carbamazepine).
Buspirone (major): CYP3A4 inhibition. Lamberg 1998 (PMID:9663178) verbatim: "Verapamil and diltiazem increased the area under the buspirone plasma concentration-time curve [AUC (0-infinity)] 3.4-fold (p < 0.001) and 5.5-fold (p < 0.001), respectively". 9 healthy volunteers, randomized 3-phase crossover, diltiazem 60 mg tid + 10 mg PO buspirone on d2. AUC 5.5×; Ki ≈ 0.5/4.5 = 0.111 µM. Cmax 4.1×; diltiazem effect significantly larger than verapamil (P < 0.05).
Midazolam (caution): CYP3A4 inhibition. Backman 1994 (PMID:8198928) verbatim: midazolam AUC "increased from 12 +/- 1 microgram ml-1 min to 45 +/- 5 micrograms ml-1 min by diltiazem (P < 0.001)". 9 healthy volunteers, double-blind 3-phase crossover, diltiazem 60 mg tid × 2d + 15 mg PO midazolam d2. AUC ratio 45/12 = 3.75×; Ki ≈ 0.5/2.75 = 0.182 µM. Cmax doubled, t½ prolonged; "Dose of midazolam should be reduced during diltiazem and verapamil treatments" per paper title.
Lovastatin (caution): CYP3A4 inhibition. Azie 1998 (PMID:9797793) verbatim: "Diltiazem significantly (P < .05) increased the oral area under the serum concentration-time curve (AUC) of lovastatin from 3607 +/- 1525 ng/ml/min (mean +/- SD) to 12886 +/- 6558 ng/ml/min". 10 healthy volunteers, randomized 4-way open-label crossover, diltiazem 120 mg bid × 2 wk + single 20 mg PO lovastatin. AUC ratio 12886/3607 = 3.57×; Ki ≈ 0.5/2.57 = 0.195 µM. Pravastatin unaffected (confirms CYP3A specificity, not transporter).