Table 2.

Comparison of the observed and simulated AUC for the adult PBPK model

	Sildenafil AUC (ng*hr/mL)			DMS AUC (ng*hr/mL)
Dosing Regimen	Simulateda	Observedb	Ratio	Simulateda	Observedb	Ratio	Reference for Observed Data
Single oral dose
25 mgb	320	361	0.89	149	147	1.01	47
50 mgb	693	738	0.94	309	328	0.94	47
100 mgb	1581	1685	0.94	659	776	0.85	47
200 mgb	3807	3755	1.01	1446	1822	0.79	47
Multiple oral dose
80 mg p.o. t.i.d.c	1209	1720	0.70	-	-	-	48
Single i.v. dose
10 mg i.v. bolusd	402	330	1.22	-	-	-	49
25 mg/25-minute infusion i.v.e	999	971	1.03	275	147	1.87	13
50 mg/50-minute infusion i.v.b	2150	1291	1.67	-	-	-	47

AUC, area under the plasma concentration vs. time curve; AUC_0–∞, area under the plasma concentration vs. time curve from 0 to infinity; AUC_0–τ, area under the plasma concentration vs. time curve from 0 to tau; DMS, N-desmethylsildenafil; PBPK, physiologically-based pharmacokinetic; t.i.d., 3 times daily.

^aSimulated values are reported as the arithmetic mean, and observed values are reported as the geometric mean.

^bHealthy men receiving 50 mg i.v. over 50 minutes and 50 mg p.o. capsule single dose plus 25, 50, 100, and 200 mg oral tablets single dose.⁴⁷

^cHealthy men receiving 20 mg t.i.d. for 3 days followed by 80 mg p.o. tablet t.i.d. for 3 days.⁴⁸

^dAdults with pulmonary arterial hypertension receiving 20 mg p.o. tablet t.i.d. for 30 days followed by 10 mg i.v. bolus.⁴⁹

^eHealthy adult men receiving 25 mg i.v. over 25 minutes single dose or 50 mg p.o. solution single dose.¹³ AUC_0–∞ was reported for 25–200 mg single oral dose, the 25 mg/25-minute infusion i.v., and the 50 mg/50-minute infusion i.v. AUC_0–τ was reported for the 80 mg p.o. t.i.d. dose and 10 mg i.v. bolus (8 hours dosing interval).