By John R. Schermerhorn, Jr., Daniel G. Bachrach
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This means that some of the earlier clinical pharmacology research on racemic mixture drugs may eventually require refinement to account for enantiomeric differences. Fortunately, the scientific ambiguities associated with chirality do not apply by and large to the clinical pharmacology of opioids. The fentanyl congeners have no chiral center and thus exist in a single form. Morphine, on the other hand, does have a center of molecular asymmetry. As a naturally occurring molecule synthesized by nature's stereospecific machinery, however, it is present in pharmacologic preparations in its 47 pure, active form (i-morphine).
This variability problem is at least partially responsible for what was until recently the generally dismal effectiveness of postoperative pain management in the eyes of patients (3). Pharmacologic variability has also no doubt contributed to the enthusiasm in the United States for the formation of acute pain management programs (4). The absence of a "one size fits all" condition in the clinical pharmacology of pain management mandates that clinicians develop a practical understanding of pharmacologic variability and a method of dealing with it in the clinical setting.
39 does not exhibit the most rapid 50% decrease in plasma concentration after termination of a continuous infusion until after approximately 8 hours of infusion. Thus, sufentanil appears to have more favorable pharmacokinetics for infusions lasting less than 8 hours when the goal is to achieve a rapid 50% decrease in concentration. In terms of pharmacokinetic theory, this surprising difference between alfentanil and sufentanil can be explained by the fact that sufentanil's pharmacokinetic model has a large, slowly equilibrating peripheral compartment that continues to fill after termination of an infusion, thus contributing to the faster decrease in sufentanil central compartment concentration.