PMID- 1831585
OWN - NLM
STAT- MEDLINE
DCOM- 19910926
LR  - 20190626
IS  - 0002-8703 (Print)
IS  - 0002-8703 (Linking)
VI  - 122
IP  - 3 Pt 1
DP  - 1991 Sep
TI  - Clinical pharmacology of intravenous enoximone: pharmacodynamics and 
      pharmacokinetics in patients with heart failure.
PG  - 755-63
AB  - Twenty-one patients with heart failure (New York Heart Association [NYHA] class 
      II to IV) received a 24-hour infusion of enoximone followed by a 12-hour washout 
      period. Patients were randomly assigned to one of four treatment groups. Groups I 
      to III received an 0.5 mg/kg bolus, followed by a maintenance infusion of 2.5, 
      5.0, or 10.0 micrograms/kg/min. Group IV patients received a maintenance infusion 
      of 5.0 micrograms/kg/min without a loading dose. Serial assessment of 
      hemodynamics, plasma levels of enoximone and enoximone sulfoxide, and ventricular 
      ectopy were performed. Enoximone produced a clinically significant increase in 
      cardiac index, and a decrease in mean pulmonary artery wedge pressure and 
      systemic vascular resistance in all groups. Enoximone mildly increased heart 
      rate, and had a minimal effect on mean arterial pressure. There was no 
      statistically significant change in ventricular ectopy during the infusion. 
      Significant hemodynamic improvement was noted at even the lowest infusion rate, 
      and did not increase in linear fashion at higher infusion rates. In patients who 
      did not receive an initial loading bolus of 0.5 mg/kg, the increase in cardiac 
      index was delayed by approximately 1 hour. Plasma concentrations of both 
      enoximone and its major metabolite continued to rise throughout the 24-hour 
      infusion in group III (10.0 micrograms/kg/min), rather than reaching steady state 
      as predicted by the terminal exponential half-lives of these compounds. This is 
      suggestive of nonlinear pharmacokinetics and indicates a potential for excessive 
      accumulation of enoximone and its metabolite during prolonged infusion. These 
      findings may have important implications in guiding the intravenous 
      administration of enoximone.(ABSTRACT TRUNCATED AT 250 WORDS)
FAU - Smith, N A
AU  - Smith NA
AD  - Cardiovascular Medicine, Sequoia Hospital, Redwood City, CA.
FAU - Kates, R E
AU  - Kates RE
FAU - Lebsack, C
AU  - Lebsack C
FAU - Ruder, M A
AU  - Ruder MA
FAU - Mead, R H
AU  - Mead RH
FAU - Bekele, T
AU  - Bekele T
FAU - Okerholm, R A
AU  - Okerholm RA
FAU - Rubin, G M
AU  - Rubin GM
FAU - Winkle, R A
AU  - Winkle RA
LA  - eng
PT  - Clinical Trial
PT  - Comparative Study
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Am Heart J
JT  - American heart journal
JID - 0370465
RN  - 0 (Imidazoles)
RN  - 0 (Phosphodiesterase Inhibitors)
RN  - C7Z4ITI7L7 (Enoximone)
SB  - IM
MH  - Aged
MH  - Dose-Response Relationship, Drug
MH  - Drug Evaluation
MH  - Enoximone
MH  - Female
MH  - Heart Failure/*drug therapy
MH  - Hemodynamics/*drug effects
MH  - Humans
MH  - Imidazoles/*pharmacokinetics/*pharmacology
MH  - Infusions, Intravenous
MH  - Male
MH  - Phosphodiesterase Inhibitors/*pharmacokinetics/*pharmacology
EDAT- 1991/09/01 00:00
MHDA- 1991/09/01 00:01
CRDT- 1991/09/01 00:00
PHST- 1991/09/01 00:00 [pubmed]
PHST- 1991/09/01 00:01 [medline]
PHST- 1991/09/01 00:00 [entrez]
AID - 0002-8703(91)90522-J [pii]
AID - 10.1016/0002-8703(91)90522-j [doi]
PST - ppublish
SO  - Am Heart J. 1991 Sep;122(3 Pt 1):755-63. doi: 10.1016/0002-8703(91)90522-j.