Effects of long-term drugs on alfentanil clearance in patients undergoing renal transplantation
Koehntop, D.E.; Noormohamed, S.E.; Fletcher, C.V.
PharmacoTherapy 14(5): 592-599
1994
ISSN/ISBN: 0277-0008 PMID: 7997393 Document Number: 431681
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 mu-g/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 (Vd-ss), and total body clearance were determined by non-compartmental methods. There was no statistical difference in the Vd-ss 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 cntdot kg-1 cntdot min-1, and elimination half-life 50.6 +- 13.9 versus 90.7 +- 22.4 minutes, respectively (p lt 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.