Table 1.

Final model: population parameters

Parameter	Estimate	% RSE	[95 % CI]	Mean prediction error (%); [95 %CI]
F 1	0.300	6.65	[0.260; 0.340]	21.7 [10.4; 33.1]
k 12 (h−1) nanosuspensions	0.259	12.1	[0.197; 0.322]	−25.0 [−29.6; −20.4]
k 12 (h−1) solution	0.299	12.6	[0.224; 0.375]	−25.0 [−29.6; −20.4]
k 13 (h−1)	0.340	5.28	[0.304; 0.376]	2.53 [−1.23; 6.29]
Q (µL/h)a	0.136	19.8	[0.0821; 0.190]	32.2 [−2.45; 66.37]
Cl nl (µL/h)b	275	9.87	[220; 329]	20.5 [−17.7; 58.7]
Cl ah (µL/h)c	231	9.58	[187; 274]	13.8 [5.09; 22.5]
V 1 (µL)	155	16.4	[104; 206]	39.7 [17.6; 61.9]
V 2 (µL)	1.24	39.3	[0.266; 2.22]	93.1 [−11.0; 196]
V 3 (µL)	42.8	5.54	[38.1; 47.6]	0.220 [−2.74; 3.18]
V 4 (µL)	218	14.5	[155; 282]	29.4 [2.98; 55.7]

	Estimate (%)	CV %	[95 % CI]—shrinkage  %
Inter-individual variability
F 1	60.5	17.6	[48.7; 70.3]—1.97
k 12	80.0	18.3	[63.8; 93.6]—91.5
k 13	45.3	16.7	[37.0; 52.3]—59.7
Q	172	17.3	[139; 199]—17.8
Cl nl	90.5	16.7	[73.9; 104]—19.2
Cl ah	92.0	16.9	[74.9; 106]—74.4
V 1	153	17.0	[124; 177]—47.4
V 2	437	18.4	[347; 511]—60.6
V 3	51.1	18.2	[40.8; 59.7]—98.5
V 4	265	18.6	[210; 311]—81.8
Residual variability
σ	0.491	107	[NA; 0.871]—99.8

CI confidence interval, NA not applicable, F ₁ relative bioavailability in the tears, k ₁₂ (h⁻¹) rate constant (tear to the naso-lacrymal duct) in nanosuspensions and in solution, k ₁₃ (h⁻¹) rate constant (tear to cornea), k ₃₄ rate constant (cornea to aqueous humor, k ₄₃ rate constant (from aqueous humor to cornea, k ₂₀ elimination rate constant from naso-lacrimal duct, k ₄₀ elimination rate constant from aqueous humor, Q (µL/h) inter-compartmental clearance (cornea/aqueous humor), Cl _nl (µL/h) clearance from naso-lacrymal duct, Cl _ah (µL/h) clearance from aqueous humor, V ₁ (µL) volume of distribution (tear), V ₂ (µL) volume of distribution of naso-lacrymal duct, V ₃ (µL) volume of distribution of cornea, V ₄ (µL) volume of distribution of the aqueous humor

^a Q = k ₃₄ × V ₃ = k ₄₃ × V ₄

^b Cl _nl = k ₂₀ × V ₂

^c Cl _ah = k ₄₀ × V ₄