RT Journal Article
SR Electronic
T1 Decreased fentanyl and alfentanil dose requirements with age. A simultaneous pharmacokinetic and pharmacodynamic evaluation.
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 159
OP 166
VO 240
IS 1
A1 J C Scott
A1 D R Stanski
YR 1987
UL http://jpet.aspetjournals.org/content/240/1/159.abstract
AB The effect of increasing age on the dose of fentanyl or alfentanil required to produce the same electroencephalographic (EEG) stage was studied in adult male patients. The pharmacokinetic and pharmacodynamic components of each patient's dose-response relationship were evaluated simultaneously. Frequent arterial blood samples drawn during and after an infusion of fentanyl or alfentanil were assayed by radioimmunoassay and permitted determination of each patient's pharmacokinetic profile. The EEG was analyzed by power spectral analysis and a parameter (spectral edge frequency) chosen to quantitate the narcotic-induced EEG slowing. An inhibitory sigmoid Emax pharmacodynamic model related spectral edge frequency to narcotic serum concentrations. The dose requirement of fentanyl or alfentanil decreased significantly with increasing age (a 50% decrease from age 20 to 89). No age-related changes in the pharmacokinetic parameters were found. Brain sensitivity (as determined by EEG changes) did decrease significantly with age. Thus, the decreased dose requirement in the elderly had a pharmacodynamic explanation, using the EEG as a measure of narcotic drug effect.