TABLE 2

Pharmacokinetic parameters and predicted extent of interaction of HIV protease inhibitors and CYP3A substrates Predicted values were based on the range of protease inhibitor concentrations, estimated inactivation parameters estimated with HLM, pharmacokinetic properties of each CYP3A substrate, and kdeg values (Correia, 1991; Malhotra et al., 2001).

Protease Inhibitor Iu CYP3A Substrate fmFGEmbedded Image
Predicted Observed
μM
Saquinavir SGC 0.02b Sildenafila 0.79b 0.38c 7.7–8.9 3.1a
Saquinavir SGC 0.004–0.038d i.v. Midazolamd 0.9d 1.00 1.8–6.5 1.0–5d
Saquinavir SGC 0.004–0.038d Oral midazolamd 0.9d 0.41d 4–14.3 3.5–9d
Ritonavir 0.21a Sildenafila 0.79b 0.38c 11.7–11.8 11a
Ritonavir 0.08e i.v. Fentanyle 0.5–0.70f,g 1.00 2.0–3.3 1.5–5.2e
Ritonavir 0.02h Triazolamh 0.8i 0.44i 10–17 20h
Ritonavir 0.02h Zolpidemh 0.6i 0.67i 3.5–3.6 1.3h
Ritonavir 0.02j Alprazolamj 0.8i 0.88i 5.1–5.3 2.5j
Ritonavir 0.03k Trazodonek 0.35l 0.75m 2.0 2.4k
  • SGC, soft gelatin capsule.

  • a Muirhead et al. (2000)

  • b Warrington et al. (2000)

  • c Thummel and Shen (2001)

  • d Palkama et al. (1999)

  • e Olkkola et al. (1999)

  • f Tateishi et al. (1995)

  • g Guitton et al. (1997)

  • h Greenblatt et al. (2000a)

  • i Rodrigues et al. (2001)

  • j Greenblatt et al. (2000b)

  • k Greenblatt et al. (2003)

  • l Jauch et al. (1976)

  • m Nilsen and Dale (1992)