[Corneal permeability of topically applied pirenzepine solution].
OBJECTIVE
To study the corneal permeability of three different pirenzepine eye-drop solutions and provide reference for further clinical use.


METHODS
Sixty-three New Zealand white rabbits were divided into three groups. Each group of rabbits received 2% pirenzepine (pirenzepine group), 2% pirenzepine with 0.1% hyaluronic acid (hyaluronic acid group), or 2% pirenzepine with 0.1% azone (azone group). One drop eye-drops was applied to conjunctive sac every 5 min for six times. Aqueous samples were obtained from each group at 0.5, 1.0, 2.0, 4.0, 8.0, 12.0, 24.0 h after the last drop, respectively. Concentration of pirenzepine in these samples was determined by the HPLC (high pressure liquid chromatography). Stimulation symptom of rabbit eyes was also observed.


RESULTS
The concentrations of pirenzepine in aqueous humor were (0.40 +/- 0.06) microg/ml at 0.5 h, (0.53 +/- 0.03) microg/ml at 1.0 h, (1.52 +/- 0.33) microg/ml at 2.0 h and (0.15 +/- 0.02) microg/ml at 4.0 h in pirenzepine group. Aqueous humor concentration of pirenzepine in both 2% pirenzepine with 0.1% azone and 2% pirenzepine with 0.1% hyaluronic acid were significantly higher than that of single pirenzepine application, and their bioavailability in the groups with combinations of pirenzepine with 0.1% azone or 0.1% hyaluronic acid were 23.0 times and 3.4 times higher than that of single pirenzepine usage. No obvious irritate symptom was found in rabbit of all three groups after eye-drop applying.


CONCLUSIONS
The combination application of pirenzepine with azone or hyaluronic acid has higher corneal permeability compared with pirenzepine alone. This result indicates that azone and hyaluronic acid could be used in pirenzepine eye-drop solution to increase corneal permeability.
Wang
Kai-di
KD
Department of Ophthalmology, First Teaching Hospital of Zhengzhou University, Zhengzhou 450052, China.
Zhang
Jin-song
JS
Yan
Pan-shi
PS
D000818:Animals; D001381:Azepines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D003315:Cornea / Q000378:metabolism*; D005260:Female; D006820:Hyaluronic Acid / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008297:Male; D018727:Muscarinic Antagonists / Q000008:administration & dosage / Q000493:pharmacokinetics*; D009883:Ophthalmic Solutions; D010539:Permeability; D010890:Pirenzepine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011817:Rabbits
D001381:Azepines; D018727:Muscarinic Antagonists; D009883:Ophthalmic Solutions; C035229:laurocapram; D010890:Pirenzepine; D006820:Hyaluronic Acid