TABLE 3

Pharmacokinetic parameters of PDA, HVA, TDA, and HDA in three cynomolgus monkeys following intravenous administration of PROB alone (40 mg/kg), FSM alone (2 mg/kg), and PROB with FSM

Pharmacokinetic parameters were determined as described in Materials and Methods. Data are shown as mean ± S.D. (n = 3). PROB was intravenously dosed 30 minutes prior to FSM administration in the coadministration treatment group.

Analyte/Parameter	PROB Alone		FSM Alone	FSM with PROB
Analyte/Parameter	Value	Ratio (90% CI)^{^a}	Value	Value	Ratio (90% CI)^{^a}
PDA
AUC_{0–24 h} (µM⋅h)	113.5 ± 23.3^*	2.8 (2.0–3.9)	40.5 ± 2.2	120.0 ± 17.9^**	2.9 (2.1–4.1)
C_max (μM)	7.3 ± 1.2^*	3.1 (2.2–4.3)	2.4 ± 0.2	7.9 ± 1.1^**	3.3 (2.3–4.8)
CL_R (ml/min per kilogram)	0.4 ± 0.2^*	0.10 (0.01–1.6)	4.9 ± 3.3	2.7 (2.2 and 3.1)^{^b},^**	0.39 (0.33 and 0.46)^{^b}
HVA
AUC_{0–24 h} (µM⋅h)	6.5 ± 1.0^*	1.6 (1.1–2.3)	4.1 ± 0.7	8.7 ± 1.9^*	2.1 (1.9–2.4)
C_max (μM)	0.68 ± 0.03^**	2.8 (2.0–3.8)	0.25 ± 0.04	0.78 ± 0.22^*	3.1 (2.1–4.6)
CL_R (ml/min per kilogram)	1.3 ± 0.5	0.8 (0.4–1.6)	1.6 ± 0.2	0.9 (0.9 and 0.8)^{^b},^*	0.50 (0.49 and 0.51)^{^b}
TDA
AUC_{0–7 h} (nM⋅h)	449 ± 233^*	2.8 (1.6–5.0)	168 ± 121	526 ± 250	3.3 (1.1–10.3)
C_max (nM)	97 ± 43^*	2.3 (1.8–3.0)	42 ± 21	195 ± 110	4.3 (1.1–17.7)
HDA
AUC_{0–7 h} (nM⋅h)	592 ± 224^*	1.9 (0.9–3.7)	355 ± 263	870 ± 321	2.7 (0.9–8.0)
C_max (nM)	148 ± 109	2.0 (1.1–3.9)	69 ± 45	223 ± 107^*	3.3 (1.7–6.6)

CI, confidence interval.
↵^a Ratio of pharmacokinetics parameter of PROB treatment to FSM treatment.
↵^b Cage malfunction prevented urine collection from one monkey in the coadministration treatment group (n = 2).
↵* P < 0.05 and
↵** P < 0.01, when the parameter was compared with that administered with FSM alone.