Effects of long-term drugs on alfentanil clearance in patients undergoing renal transplantation.

Abstract

Although patients in renal failure frequently take several drugs on a long-term basis, drug-induced alterations in alfentanil metabolism have not been examined as a possible source of variability in alfentanil clearance in this population. We compared the pharmacokinetics of alfentanil during renal transplantation in seven patients receiving and six not receiving long-term drug therapy. After the rapid intravenous injection of alfentanil 100 micrograms/kg during isoflurane anesthesia, plasma concentrations were measured at intervals up to 6 hours by radioimmunoassay. The terminal elimination half-life, steady-state volume of distribution (Vdss), and total body clearance were determined by noncompartmental methods. There was no statistical difference in the Vdss between the two patient groups. However, clearance was significantly higher and elimination half-life lower in the group taking long-term drugs: clearance 6.94 +/- 4.64 versus 3.47 +/- 0.16 ml.kg-1.min-1, and elimination half-life 50.6 +/- 13.9 versus 90.7 +/- 22.4 minutes, respectively (p < 0.05). The higher clearance occurred even though five of the seven patients were taking agents known to be metabolized by the same cytochrome P-450 hepatic isozyme that metabolizes alfentanil and therefore potential competitive inhibitors of alfentanil metabolism. Drugs taken by the three patients with the highest alfentanil clearances included known inducers of hepatic drug metabolism. Thus, in the presence of several long-term drugs, the clearance of alfentanil appears to be noticeably increased by inducers of hepatic drug metabolism but unaffected by potential competitive inhibitors.