Table I.

Summary of the Input Parameters Employed for the Gastroplus Simulation

	Parameter	Valuea
Physiochemical	1. Molecular weight (Da)	259.4
	2. Solubility (mg/ml)	1.66 (at pH 10.5)
	3. Log P	2.93
	4. pK a	9.23
Formulation	5. Mean precipitation time (s)	900
	6. Drug particle density (g/L)	1.2
	7. Effective particle radium (mm)	25
Pharmacokinetics	8. Dose (mg)	8.8, 35.2
	9. Dose volume (mL)	1
	10. Body weight (kg)	65.5
	11. Simulation time (h)	7b
	12. Diffusion coefficient (×10−5 cm2/s)	0.83
	13. P eff (×10−4 cm/s)	3.74c
	14. Unbound percent in plasma (%)	8.08
	15. Blood/plasma concentration ratio	1
	16. First pass extraction (%)	62.89d
	17. Clearance (L/h/kg)	1.08
	18. Volume distribution (L/kg)	1.12
	19. Elimination half-life (h)	2.91
	20. K 12 (1/h)	13.24
	21. K 21 (1/h)	4.60
	22. V 2 (L/kg)	3.22

^aExcept for item 8 (dose), the values of parameters 1–15 are input values based on ADMET predictor (version 2.3.0) used by Gastroplus (version 6.0), whereas items 16–22 are optimized values generated to achieve best fit after using initial values estimated from IV propranolol (see (17))

^bFor sublingual administration, total simulation duration is 7 h with 0.25 h sublingual absorption, followed by swallowing of saliva with dissolved drug, i.e., gastrointestinal absorption

^cPeff stands for effective permeation

^dReduced to 47% with 40 mg dose administration