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 | fm | FG | ![]() | |
---|---|---|---|---|---|---|
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)