Effect of Lercanidipine on the Pharmacokinetics-Pharmacodynamics of Carvedilol Enantiomers in Patients With Chronic Kidney Disease

Author(s)

Schaab, Estela Hanauer ^[1] ; Lanchote, Vera Lucia ^[1] ; Balthazar Nardotto, Glauco Henrique ^[1] ; Marques Pereira, Maria Paula ^[1] ; Dantas, Marcio ^[2] ; Paiva, Carlos Eduardo ^[2] ; Coelho, Eduardo Barbosa ^[2]

Affiliation

^[1] Univ Sao Paulo, Fac Ciencias Farmaceut Ribeirao Preto, Ribeirao Preto - Brazil

^[2] Univ Sao Paulo, Fac Med Ribeirao Preto, Ribeirao Preto - Brazil

• Document type: Journal article
• Source: Journal of Clinical Pharmacology; v. 60, n. 1, p. 75-85, JAN 2020.
• Web of Science Citations: 0

Abstract

This study evaluates the carvedilol-lercanidipine drug interaction, and the influence of chronic kidney disease (CKD) on both drugs. Patients with high blood pressure (8 with normal renal function {[}control] and 8 with CKD with estimated glomerular filtration rate categories of G3b to G5 {[}12-38 mL/min/1.73 m2]) were included and prescribed 3 different treatment regimens, a single oral dose of racemic carvedilol 25 mg (CAR), a single oral dose of racemic lercanidipine 20 mg (LER), and single oral doses of CAR plus LER. Blood samples were collected and variations in heart rate were assessed (using isometric exercise with handgrip) for up to 32 hours. Lercanidipine pharmacokinetics were not enantioselective, and were not affected by carvedilol and CKD. Carvedilol pharmacokinetics (data presented as median) were enantioselective with higher plasma exposure of (R)(+)-carvedilol in both control (103.5 vs 46.0 ng . h/mL) and CKD (190.6 vs 98.9 ng . h/mL) groups. Lercanidipine increased the area under the plasma concentration-time curve of only (R)-(+)-carvedilol in the CKD group (190.6 vs 242.2 ng . h/mL) but not in the control group (103.5 vs 98.7 ng . h/mL). CKD increased plasma exposure (46.0 vs 98.9 ng . h/mL) and effect-compartment exposure (5.5 vs 20.9 ng . h/mL) to (S)-(-)carvedilol, resulting in higher beta-adrenergic inhibition (10.0 vs 6.1 bpm). Therefore, carvedilol dose titration in CKD patients with estimated glomerular filtration rate categories of G3b to G5 should be initiated, with no more than half the dose used for patients with normal renal function. (AU)

• FAPESP's process: 08/04840-5 - Lercanidipine-carvedilol interaction: stereoselectivity and influence of chronic renal failure in hypertensive patients
• Grantee: Estela Hanauer Schaab
• Support Opportunities: Scholarships in Brazil - Doctorate