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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\u201038 mL\/min\/1.73 m<jats:sup>2<\/jats:sup>]) 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)\u2010(+)\u2010carvedilol in both control (103.5 vs 46.0 ng \u2219 h\/mL) and CKD (190.6 vs 98.9 ng \u2219 h\/mL) groups. Lercanidipine increased the area under the plasma concentration\u2013time curve of only (R)\u2010(+)\u2010carvedilol in the CKD group (190.6 vs 242.2 ng \u2219 h\/mL) but not in the control group (103.5 vs 98.7 ng \u2219 h\/mL). CKD increased plasma exposure (46.0 vs 98.9 ng \u2219 h\/mL) and effect\u2010compartment exposure (5.5 vs 20.9 ng \u2219 h\/mL) to (S)\u2010(\u2013)\u2010carvedilol, resulting in higher \u03b2\u2010adrenergic 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.<\/jats:p>","DOI":"10.1002\/jcph.1485","type":"journal-article","created":{"date-parts":[[2019,7,29]],"date-time":"2019-07-29T06:14:19Z","timestamp":1564380859000},"page":"75-85","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Effect of Lercanidipine on the Pharmacokinetics\u2010Pharmacodynamics of Carvedilol Enantiomers in Patients With Chronic Kidney Disease"],"prefix":"10.1002","volume":"60","author":[{"given":"Estela","family":"Hanauer Schaab","sequence":"first","affiliation":[{"name":"Faculdade de Ci\u00eancias Farmac\u00eauticas de Ribeir\u00e3o Preto Universidade de S\u00e3o Paulo  Ribeir\u00e3o Preto Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vera 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