Radioimmunoassay of the new opiate analgesics alfentanil and sufentanil. Preliminary pharmacokinetic profile in man.

Abstract

The development of two analogous radioimmunoassay (RIA) procedures based on dextran-charcoal separation is described for the quantification of two fentanyl-like analgesics, alfentanil and sufentanil. Immunization of rabbits with conjugates of bovine serum albumin and carboxy-derivatives of the respective drugs resulted in the production of antisera capable of detecting less than 0.05 ng ml-1 of the parent analgesics with high specificity and almost no cross-reactivity with major metabolites. Excellent agreement was obtained between RIA--without prior extraction--and gas chromatography for alfentanil concentrations in human plasma. Because of sufentanil's low therapeutic plasma levels, no comparison could be made between its RIA and an alternative assay, however, there was strong evidence for the specificity of the assay when applied directly to plasma. With these RIA methods preliminary information was obtained on plasma concentrations and elimination of alfentanil or sufentanil in patients given an intravenous bolus injection of 50 micrograms kg-1 of alfentanil, or 5 micrograms kg-1 of sufentanil. For both analgesics, the pharmacokinetic profile in man could be described by a three-compartment model. The terminal elimination half-life was 88 min for alfentanil and 140 min for sufentanil. Six hours after a therapeutic dose, plasma levels were in the order of 3 and 0.3 ng ml-1 for alfentanil and sufentanil respectively.