Relationship of duration of analgesia to opioid pharmacokinetic variables

That physiological effects are directly related to concentration at the site of action has been validated for only a few classes of drugs. For opiates, a direct correlation is known to exist between concentration and magnitude of analgesia, but has not been shown for duration of analgesia. These experiments in rats, using opiates whose elimination half-lives differ by a factor of 2 1/2, in a range of doses that produce 10-90% of maximal analgesic effect, show that duration is not dependent on dose or rate of elimination of opiate analgesics. The data suggest that analgesic duration is not determined by the pharmacokinetics of opiates at the receptors where these drugs act to elicit analgesia.