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 k_deg values (Correia, 1991; Malhotra et al., 2001).

Protease Inhibitor	I_u	CYP3A Substrate	f_m	F_G
Protease Inhibitor	I_u	CYP3A Substrate	f_m	F_G	Predicted	Observed
	μM
Saquinavir SGC	0.02^b	Sildenafil^a	0.79^b	0.38^c	7.7–8.9	3.1^a
Saquinavir SGC	0.004–0.038^d	i.v. Midazolam^d	0.9^d	1.00	1.8–6.5	1.0–5^d
Saquinavir SGC	0.004–0.038^d	Oral midazolam^d	0.9^d	0.41^d	4–14.3	3.5–9^d
Ritonavir	0.21^a	Sildenafil^a	0.79^b	0.38^c	11.7–11.8	11^a
Ritonavir	0.08^e	i.v. Fentanyl^e	0.5–0.70^f^,^g	1.00	2.0–3.3	1.5–5.2^e
Ritonavir	0.02^h	Triazolam^h	0.8ⁱ	0.44ⁱ	10–17	20^h
Ritonavir	0.02^h	Zolpidem^h	0.6ⁱ	0.67ⁱ	3.5–3.6	1.3^h
Ritonavir	0.02^j	Alprazolam^j	0.8ⁱ	0.88ⁱ	5.1–5.3	2.5^j
Ritonavir	0.03^k	Trazodone^k	0.35^l	0.75^m	2.0	2.4^k

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)