ISSN:
1432-1041
Keywords:
Key words Carvedilol
;
Hypertension
;
Renal insufficiency
Source:
Springer Online Journal Archives 1860-2000
Topics:
Chemistry and Pharmacology
,
Medicine
Notes:
Abstract Introduction: Carvedilol, a chiral compound possessing nonselective β- and α1-blocking activity, is used for the treatment of hypertension and congestive heart failure (CHF). The enantiomers of carvedilol exhibit similar α1-blocking activity; only S-carvedilol possesses β-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 ≤ 30 ml · 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 · h · 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 · 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 β-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.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/s002280050628
Permalink
