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Boyle DA, Gehr TW, Qian Y, et al. The pharmacokinetics of carvedilol and its metabolites after single and multiple dose oral administration in patients with hypertension and renal insufficiency. Eur J Clin Pharmacol. 1999;55(4):269-77doi: 10.1007/s002280050628.
Boyle, D. A., Gehr, T. W., Qian, Y., Shusterman, N. H., Sica, D. A., & Tenero, D. M. (1999). The pharmacokinetics of carvedilol and its metabolites after single and multiple dose oral administration in patients with hypertension and renal insufficiency. European journal of clinical pharmacology, 55(4), 269-77. https://doi.org/10.1007/s002280050628
Boyle, D A, et al. "The pharmacokinetics of carvedilol and its metabolites after single and multiple dose oral administration in patients with hypertension and renal insufficiency." European journal of clinical pharmacology vol. 55,4 (1999): 269-77. doi: https://doi.org/10.1007/s002280050628
Boyle DA, Gehr TW, Qian Y, Shusterman NH, Sica DA, Tenero DM. The pharmacokinetics of carvedilol and its metabolites after single and multiple dose oral administration in patients with hypertension and renal insufficiency. Eur J Clin Pharmacol. 1999 Jun;55(4):269-77. doi: 10.1007/s002280050628. PMID: 10424319.
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Eur J Clin Pharmacol. 1999 Jun;55(4):269-77. doi: 10.1007/s002280050628.

The pharmacokinetics of carvedilol and its metabolites after single and multiple dose oral administration in patients with hypertension and renal insufficiency.

European journal of clinical pharmacology

D A Boyle, T W Gehr, Y Qian, N H Shusterman, D A Sica, D M Tenero

Affiliations

  1. Division of Clinical Pharmacology and Hypertension, and Nephrology, Virginia Commonwealth University, Medical College of Virginia, Richmond, USA.

PMID: 10424319 DOI: 10.1007/s002280050628

Abstract

INTRODUCTION: Carvedilol, a chiral compound possessing nonselective beta- and alpha1-blocking activity, is used for the treatment of hypertension and congestive heart failure (CHF). The enantiomers of carvedilol exhibit similar alpha1-blocking activity; only S-carvedilol possesses beta-blocking activity. Carvedilol is primarily hepatically metabolized, with less than 2% of the dose excreted renally as unchanged drug.

METHODS: The pharmacokinetics of carvedilol, R-carvedilol, and S-carvedilol were studied in hypertensive patients (control; n = 13) versus patients with hypertension and advanced renal insufficiency not yet on dialysis [GFR < or = 30 ml x min(-1) (CRI, chronic renal insufficiency), n = 12] following single (12.5 mg, Day 1) and multiple (25 mg once daily, Days 2 9) dosing.

RESULTS: Mean with (SD) AUC(0-24h) (ng x h x ml(-1)) for carvedilol was 220 (120) and 618 (335) in CRI compared with 165 (83.5) and 413 (247) in controls on Days 1 and 9, respectively, primarily due to higher R-carvedilol concentrations. Mean with (SD) Cmax (ng x ml(-1)) for carvedilol were 53.4 (31.4) and 128 (63.3) in CRI compared with 46.7 (23.3) and 104 (58.9) in controls on Days 1 and 9, respectively. The difference in group mean values was characterized by considerable overlap in individual AUC(0-24h) and Cmax values between groups. There was no apparent difference in mean terminal elimination half-life for carvedilol between groups on each study day. Less than 1% of the dose was excreted in urine as unchanged carvedilol in both groups. Blood pressure and heart rate declined in both groups to a similar degree.

CONCLUSION: Compared with controls, average AUC(0-24 h) values for carvedilol were approximately 40% and 50% higher on study Days 1 and 9 in patients with renal insufficiency, primarily due to higher R-carvedilol concentrations with only a small change (<20%) in S-carvedilol concentrations, the isomer possessing beta-blocking activity. These changes in pharmacokinetics are modest in view of the large interindividual variability. Carvedilol was well tolerated in both groups. Although the present study cannot provide a final conclusion, based on the results of the present study, no changes in dosing recommendations for carvedilol are warranted in patients with moderate/severe renal insufficiency.

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