Pharmacokinetics and Pharmacodynamics of Sterylglucoside-Modified Liposomes for Levonorgestrel Delivery via Nasal Route

Figures & data

FIG. 1 Mean levonorgestrel plasma concentrations versus time profiles for oral and nasal administration (mean ± SD, n = 4). ♦-LNG suspension by oral administration at 500 μg/rat; ▴-EPC/SG/LNG by nasal administration at 500 μg/rat; ▵-EPC/SG/LNG/chitosan by nasal administration at 500 μg/rat; •-EPC/SG/LNG by nasal administration at 350 μg/rat; ▪-EPC/Ch/LNG by nasal administration at 350 μg/rat.

TABLE 1 Pharmacokinetic parameters of different levonorgestrel (LNG) formulations after oral or nasal administration in rats*

	Administration	Dose/rat	AUC0 − 12	F**	Cmax	Tmax	T1/2
Formulations	route	(μ g)	(ng · h/mL)	(%)	(ng/mL)	(h)	(h^−1)
LNG suspension	Oral	500	1294.87 ± 494.19	—	334.94 ± 24.70	1.89 ± 0.09	1.38 ± 0.34
EPC/Ch/LNG	Nasal	350	900.30 ± 103.83	99.33 ± 11.45	184.59 ± 20.05	1.43 ± 0.34 ^††	3.16 ± 0.68
			1285.71 ± 148.33***		263.70 ± 28.64^†, ††
EPC/SG/LNG	Nasal	350	1035.07 ± 101.68	114.19 ± 11.22	264.74 ± 11.29	1.04 ± 0.41^††	3.00 ± 0.49
			1478.67 ± 145.26***		378.20 ± 16.13^†, ††
EPC/SG/LNG	Nasal	500	1303.09 ± 114.05	110.64 ± 8.81	416.84 ± 48.07^††	1.00 ± 0.30^††	3.28 ± 0.24
EPC/SG/LNG/	Nasal	500	1482.50 ± 49.00	114.49 ± 3.87	227.97 ± 56.59^††, †††	2.02 ± 0.43^†††	4.49 ± 1.88
chitosan

EPC = egg phosphatidylcholine, ch = cholesterol, SG = sterylglucoside.

*Each value represents the mean ± S.D. (n = 4). **F = (dose_oral · AUC_{0-12 nasal}/dose_nasal · AUC_{0-12 oral}) × 100%. ***Values are calculated as AUC₀₋₁₂ × 500/350 in to compare conveniently. ^†Values are calculated as C_max × 500/350 to compare conveniently. ^††Significant difference in the mean values was evaluated by Student's t-test vs. LNG suspension by oral route (p < 0.05). ^†††Significant difference in the mean values was evaluated by Student's t-test vs. EPC/SG/LNG by nasal route (p < 0.01).

TABLE 2 Contraceptive effects with different levonorgestrel (LNG) formulations

Formulations	Administration route	Dose (μ g/rat)	Number rats mated	Number rats pregnant
Control	—	0	10/10	10/10
LNG suspension	Oral	350	10/10	0/10
EPC/Ch/LNG	Nasal	350	10/10	0/10
EPC/SG/LNG	Nasal	350	10/10	0/10
EPC/SG/LNG/chitosan	Nasal	350	10/10	0/10

EPC = egg phosphatidylcholine, Ch = cholesterol, SG = sterylglucoside.