Table 2.

PK parameters obtained with the compartmental model describing the hepatobiliary disposition of [¹¹C]tariquidar, [¹¹C]erlotinib, and [¹¹C]elacridar in wild-type, Abcb1a/b^(−/−), Abcg2^(−/−), and Abcb1a/b^(−/−)Abcg2^(−/−) mice.

Radiotracer	Parameter	Wild-Type	Abcb1a/b(−/−)	Abcg2(−/−)	Abcb1a/b(−/−)Abcg2(−/−)
[11C]tariquidar	CL1 (mL/min)	2.2798 ± 0.5058 (12.9–32.3)	1.7207 ± 0.1377 (10.7–23.1)	1.5836 ± 0.1993 (9.6–22.1)	1.9316 ± 0.6933 (9.6–34.2)
	k2 (min−1)	0.2600 ± 0.0475 (11.0–26.4)	0.2421 ± 0.0227 (10.5–19.0)	0.3244 ± 0.0204 (9.0–20.5)	0.3441 ± 0.1549 (9.0–29.7)
	k3 (min−1)	0.0036 ± 0.0004 (4.1–7.6)	0.0039 ± 0.0002 (4.2–7.6)	0.0037 ± 0.0007 (2.8–9.1)	0.0019 ± 0.0004 * (5.3–8.4)
[11C]erlotinib	CL1 (mL/min)	5.9437 ± 2.4249 (5.3–51.5)	5.2978 ± 1.8375 (12.1–45.4)	6.3856 ± 1.7690 (10.6–33.4)	7.3708 ± 0.2309 (20.7–36.7)
	k2 (min−1)	0.6431 ± 0.2567 (5.1–47.3)	0.5815 ± 0.1818 (10.8–41.4)	0.6051 ± 0.0664 (10.7–30.8)	0.5484 ± 0.1021 (17.6–32.2)
	k3 (min−1)	0.0193 ± 0.0025 (1.2–4.2)	0.0191 ± 0.0067 (1.7–4.7)	0.0091 ± 0.0011 * (1.9–3.3)	0.0069 ± 0.0018 * (2.4–4.1)
[11C]elacridar	CL1 (mL/min)	0.5338 ± 0.1759 (6.0–14.3)	0.6887 ± 0.1939 (11.3–22.4)	0.4304 ± 0.1392 (4.0–21.0)	0.5777 ± 0.2241 (4.9–24.6)
	k2 (min−1)	0.1121 ± 0.0641 (7.7–13.5)	0.1872 ± 0.1165 (10.5–17.5)	0.1674 ± 0.1366 (4.8–20.6)	0.1426 ± 0.0728 (7.1–18.8)
	k3 (min−1)	0.0040 ± 0.0008 (4.0–6.8)	0.0042 ± 0.0008 (5.2–8.9)	0.0043 ± 0.0010 (3.2–18.6)	0.0015 ± 0.0006 * (7.0–23.3)

Data are given as mean ± SD (n = 4–5 per group). Values in parentheses represent the range in percent coefficient of variation (%CV), which determines the parameter precision. PK parameters were obtained with the liver PK model. CL₁ defines the hepatic uptake clearance, and k₂ and k₃ are the rate constants defining the transfer of radioactivity from liver to the sink compartment (blood) and from liver to excreted bile, respectively. * p ≤ 0.01, one-way ANOVA followed by a Dunnett’s multiple comparison test against the wild-type group.