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Ocular pharmacokinetics of radioactive dapiprazole after topical and parenteral administration
i.m. and nasal spray administration, respectively. ~abi~ty after nasal spray administration was about 53% and 88% for the doses of 40 and 80 MRC of when compared to the availability after i.m. administration.
88%
53%
100%
Rel%tiveavailabiity
Bianchi, E. and Segre, G. htitute
of
Pharmacology, University of Siena. Via delle Scotte n. 6, 53100 Siena, Ita&
Dapiprazole is a drug which presents a alpha, adrenergic blocking activity and is used in the treatment of glaucoma; therefore the present authors have applied a pharmacokinetic analysis to the experimental data by Valeri et al. (1986) in order to investigate the distribution of dapiprazole in different ocular sites after parenteral and topical administration. The kinetics of radioactivity distribution in rabbit was measured at hour 0.25,0.5, 1, 2, 4, 8 after i.v. injection and topical application of 3H-dapiprazole in the following ocular regions; lens, aqueous humor, vitreous humor, ciliary body, iris, retina, cornea. The area under curve (AUCZ) and the mean residence time (MRT) of each considered oclllar site following parenteral and topical administration are reported in the following table. The k,, A____I-_ ____~_._~ I___- _._____ represent the uansIer constant Irom plasma and from cornea to the considered ocuiar region respeciiveiy for parenteral and topical route and were calculated on the base of the model described in Lorenzon et al., 1990.
Lens Acqueous humor Vitreous humor Iris Ciliary bodies Retina Cornea
AUG i.v. 0w’mJ h)
AU= (w/ml
2369 31029 4477 139000 144769 13539 10563
4199 103714 1117 36048 14006 1167 29719
top. h)
MRT i.v. (h)
MRT top. (h)
k,, i.v. (h--l)
2.5 12.3 23.6 12.9 14.1 2.2 9.7
20.9 96.4 95.0 83.2 3.08 0.03 3.20
O,O7 0.31 0.34 2.20 6.48 2.17 5.98
k,, top. (h-‘1 0,038 1.608 0.024 5.500 1.160 0.073
Following topical instillation, the AUC values of cornea, acqueous humor and lens are high as compared to those foollowing parenteral administration whereas the AUC values of vitreous humor, ciliary bodies, iris and retina are low. Lens, aqueous humor, vitreous humor and iris present a high MRT value after topical administration with respect to the parenteral route.
Lmenmn, F., E. Bianchi, 6. Segre. Pharmacokinetics of radioactive bendazac lysinate distribution in plasrza and different ocular regions after i.v. administration in rabbit, XIth Congress of Pharmacology, Amsterdam, 1-6 July, 1990. Valti, P., M. Palmery. G. Severini, D. Piccinelli and B. Catanese, 1986. Ocular Pharmacokinetics of Dapiprazole, Pharm. Res. Comm.. 18, 1093.
88%
53%
100%
Rel%tiveavailabiity
Bianchi, E. and Segre, G. htitute
of
Pharmacology, University of Siena. Via delle Scotte n. 6, 53100 Siena, Ita&
Dapiprazole is a drug which presents a alpha, adrenergic blocking activity and is used in the treatment of glaucoma; therefore the present authors have applied a pharmacokinetic analysis to the experimental data by Valeri et al. (1986) in order to investigate the distribution of dapiprazole in different ocular sites after parenteral and topical administration. The kinetics of radioactivity distribution in rabbit was measured at hour 0.25,0.5, 1, 2, 4, 8 after i.v. injection and topical application of 3H-dapiprazole in the following ocular regions; lens, aqueous humor, vitreous humor, ciliary body, iris, retina, cornea. The area under curve (AUCZ) and the mean residence time (MRT) of each considered oclllar site following parenteral and topical administration are reported in the following table. The k,, A____I-_ ____~_._~ I___- _._____ represent the uansIer constant Irom plasma and from cornea to the considered ocuiar region respeciiveiy for parenteral and topical route and were calculated on the base of the model described in Lorenzon et al., 1990.
Lens Acqueous humor Vitreous humor Iris Ciliary bodies Retina Cornea
AUG i.v. 0w’mJ h)
AU= (w/ml
2369 31029 4477 139000 144769 13539 10563
4199 103714 1117 36048 14006 1167 29719
top. h)
MRT i.v. (h)
MRT top. (h)
k,, i.v. (h--l)
2.5 12.3 23.6 12.9 14.1 2.2 9.7
20.9 96.4 95.0 83.2 3.08 0.03 3.20
O,O7 0.31 0.34 2.20 6.48 2.17 5.98
k,, top. (h-‘1 0,038 1.608 0.024 5.500 1.160 0.073
Following topical instillation, the AUC values of cornea, acqueous humor and lens are high as compared to those foollowing parenteral administration whereas the AUC values of vitreous humor, ciliary bodies, iris and retina are low. Lens, aqueous humor, vitreous humor and iris present a high MRT value after topical administration with respect to the parenteral route.
Lmenmn, F., E. Bianchi, 6. Segre. Pharmacokinetics of radioactive bendazac lysinate distribution in plasrza and different ocular regions after i.v. administration in rabbit, XIth Congress of Pharmacology, Amsterdam, 1-6 July, 1990. Valti, P., M. Palmery. G. Severini, D. Piccinelli and B. Catanese, 1986. Ocular Pharmacokinetics of Dapiprazole, Pharm. Res. Comm.. 18, 1093.