Decreased Fentanyl and Alfentanil Dose Requirements with Age. A Simultaneous Pharmacokinetic and Pharmacodynamic Evaluation

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.