EFFECTS OF LONG-TERM DRUGS ON ALFENTANIL CLEARANCE IN PATIENTS UNDERGOING RENAL-TRANSPLANTATION

Although patients in renal failure frequently take several drugs on a long-term basis, drug-induced alterations in alfentanil metabolism hav e not been examined as a possible source of variability in alfentanil clearance in this population. We compared the pharmacokinetics of alfe ntanil during renal transplantation in seven patients receiving and si x not receiving long-term drug therapy. After the rapid intravenous in jection of alfentanil 100 mu g/kg during isoflurane anesthesia, plasma concentrations were measured at intervals up to 6 hours by radioimmun oassay. The terminal elimination half-life, steady-state volume of dis tribution (Vd(ss)), and total body clearance were determined by noncom partmental methods. There was no statistical difference in the Vd(ss) between the two patient groups. However, clearance was significantly h igher and elimination half-life lower in the group taking long-term dr ugs. clearance 6.94 +/- 4.64 versus 3.47 +/- 0.16 ml.kg(-1).min(-1), a nd elimination half-life 50.6 +/- 13.9 versus 90.7 +/- 22.4 minutes, r espectively (p<0.05). The higher clearance occurred even though five o f 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 clearanc es included known inducers of hepatic drug metabolism Thus, in the pre sence 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.