Relationship between positive inotropic responses and plasma concentrations of xamoterol in middle-aged and elderly patients.
1. We examined the relationship between the contractile state of the left ventricle and the plasma concentration of xamoterol in patients with ischaemic heart failure. 2. Identical studies were conducted in 14 middle-aged (all male; mean age 51.3 years, range 42-61) and 10 elderly patients (six male, four female; mean age 67.7 years, range 64-72). 3. Patients received seven cumulative doses (0.0005-0.2 mg kg-1) of xamoterol. After each dose the rate of change of pressure in the left ventricle at a developed pressure of 40 mm Hg and normalised for this pressure, (dP/dt)/DP40, and plasma concentrations of xamoterol were measured. 4. There were dose-related increases in (dP/dt)/DP40. Curves relating changes in (dP/dt)/DP40, expressed as a percent of the maximum observed response, to changes in xamoterol plasma concentrations were constructed for the middle-aged and elderly patients. From these curves the mean effective concentration (EC) value to produce a particular response could be calculated. In the sample sizes studied, the difference between the EC values over a range of responses for the middle-aged and elderly patients did not reach statistical significance, indicating that cardiac responsiveness to xamoterol was similar in the two groups of patients. 5. Plasma concentrations of xamoterol over the range of 39 to 150 ng ml-1 produced positive inotropic responses which varied between 70% and 90% of the maximum observed effect of xamoterol.
Marlow
H F
HF
Medical Research Department, ICI Pharmaceuticals, Alderley Park, Cheshire.
Hine
F L
FL
Snow
H M
HM
Pouleur
H
H
Rousseau
M F
MF
D000328:Adult; D000368:Aged; D000375:Aging / Q000502:physiology*; D003327:Coronary Disease / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009200:Myocardial Contraction / Q000187:drug effects*; D011412:Propanolamines / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology*; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology; D017307:Xamoterol
D011412:Propanolamines; D017307:Xamoterol