PMID- 10934668
OWN - NLM
STAT- MEDLINE
DCOM- 20001130
LR  - 20220318
IS  - 0091-2700 (Print)
IS  - 0091-2700 (Linking)
VI  - 40
IP  - 8
DP  - 2000 Aug
TI  - Steady-state pharmacokinetics of carvedilol and its enantiomers in patients with 
      congestive heart failure.
PG  - 844-53
AB  - Carvedilol is a relatively new drug with beta- and alpha 1-receptor blocking 
      activity and antioxidant effects recently approved for the treatment of 
      congestive heart failure (CHF). An ascending, multiple-dose study was completed 
      in 20 male patients with stable New York Heart Association (NYHA) Class III or IV 
      CHF. The pharmacokinetics of carvedilol, S(-)-carvedilol, R(+)-carvedilol, and 
      the active metabolites of carvedilol was assessed at steady state after 
      twice-daily oral administration of carvedilol for 7 days at 6.25, 12.5, 25, and 
      50 mg doses. Carvedilol exhibited stereoselective pharmacokinetics in CHF 
      patients with dose-proportional increases in steady-state plasma concentrations 
      of carvedilol and its enantiomers. Mean AUC and Cmax values for carvedilol were 
      up to twofold higher in patients with Class IV CHF as compared to those with 
      Class III CHF. Steady-state plasma concentrations of the active metabolites also 
      increased in a dose-proportional manner and were typically 10% or less of that 
      observed for carvedilol. In general, carvedilol was adequately tolerated by adult 
      male CHF patients at the dose levels (6.25-50 mg) evaluated in this study as 
      adverse events were consistent with those frequently observed in patients with 
      CHF.
FAU - Tenero, D
AU  - Tenero D
AD  - Department of Drug Metabolism and Pharmacokinetics, SmithKline Beecham 
      Pharmaceuticals, King of Prussia, Pennsylvania 19406, USA.
FAU - Boike, S
AU  - Boike S
FAU - Boyle, D
AU  - Boyle D
FAU - Ilson, B
AU  - Ilson B
FAU - Fesniak, H F
AU  - Fesniak HF
FAU - Brozena, S
AU  - Brozena S
FAU - Jorkasky, D
AU  - Jorkasky D
LA  - eng
PT  - Journal Article
PL  - England
TA  - J Clin Pharmacol
JT  - Journal of clinical pharmacology
JID - 0366372
RN  - 0 (Antihypertensive Agents)
RN  - 0 (Carbazoles)
RN  - 0 (Propanolamines)
RN  - 0K47UL67F2 (Carvedilol)
SB  - IM
MH  - Adult
MH  - Antihypertensive Agents/*pharmacokinetics
MH  - Area Under Curve
MH  - Carbazoles/adverse effects/*pharmacokinetics
MH  - Carvedilol
MH  - Heart Failure/*drug therapy/metabolism
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Propanolamines/adverse effects/*pharmacokinetics
MH  - Stereoisomerism
EDAT- 2000/08/10 11:00
MHDA- 2001/02/28 10:01
CRDT- 2000/08/10 11:00
PHST- 2000/08/10 11:00 [pubmed]
PHST- 2001/02/28 10:01 [medline]
PHST- 2000/08/10 11:00 [entrez]
AID - 10.1177/00912700022009576 [doi]
PST - ppublish
SO  - J Clin Pharmacol. 2000 Aug;40(8):844-53. doi: 10.1177/00912700022009576.