Effect of Delavirdine on Protease Inhibitor Concentrations

• In contrast to other NNRTI agents, delavirdine is a CYP3A4 inhibitor, and will enhance PI levels

Clin Pharmacokinet 2001;40(3):207-226.

% ? vs. PI alone

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• Besides using dual protease inhibitor combinations, other agents with enzyme inhibiting properties may also increase protease inhibitor concentrations.

• One such agent is delavirdine, which is a potent inhibitor of CYP3A4

• Advantages of combining delavirdine with a protease inhibitor include:
  • improved protease inhibitor bioavailability
  • possibility of simplified dosing regimens
  • ability to use lower protease inhibitor doses
  • pharmacodynamic/virologic advantage of using two agents with different mechanisms of action

• DLV + Indinavir: With IDV 600 mg q8h + DLV, IDV AUC & Cmin vs. values obtained with IDV 800 mg q8h alone. Thus, use IDV 600 mg q8h with delavirdine.

• DLV + Nelfinavir: DLV 600 mg TID + standard NFVresults in approx. 2-fold increase in NFV AUC, and DLV Cmin similar to that with DLV 400 mg TID alone. Recommendations on dosage adjustments not available. Use together with caution and monitor for drug toxicities, incl. neutropenia. Regimens currently being studied: NFV 750 mg TID + DLV 600 mg TID, and NFV 1250 mg BID + DLV 600 mg BID.

• DLV + Ritonavir: 70% increase in RTV concentrations; kinetics of delavirdine and its metabolite unchanged. Recommendations on dosage adjustments not available.

• DLV + Saquinavir: 5-fold increase in SQV Cmin; monitor LFTs during initial weeks of combination therapy. Dosage adjustments not necessary.