The effects of topical and general anesthesia on ocular drug levels and intraocular pressure lowering activity of topically applied carbonic anhydrase inhibitors.
Treatment with topical anesthetics was reported to increase corneal permeability and improve ocular drug bioavailability. These changes were attributed to the loss of reflex blinking, reduction of tear secretion and appearance of superficial corneal epithelial lesions. A recent report showed that pretreatment with Ophthetic (0.5% proparacaine HCl) (OPH) in pentobarbital-anesthetized rabbits significantly increased the permeability of the lipophobic carbonic anhydrase inhibitor (CAI) benzolamide (B) and transformed it to a highly active ocular hypotensive drug. This did not affect the permeability and activity of other, more lipophilic, CAI like methazolamide and ethoxzolamide (E). Similar experiments in awake rabbits using other CAI failed to reproduce the finding reported for B. We compared the ocular drug levels and the intraocular pressure lowering (delta IOP) with and without application of Ophthetic prior to 1 drop of 2% suspensions, in groups of anesthetized and conscious albino rabbits. In unanesthetized rabbits pretreatment with Ophthetic, lidocaine or benzalkonium had minimal and insignificant effects on ocular drug levels and delta IOP of B as well as E. On the other hand, Ophthetic or lidocaine pretreatment in anesthetized rabbits led to a highly significant increase in both ocular drug levels and hypotensive activity of B. We conclude that the error introduced by pretreatment with OPH occurs only in the presence of pentobarbital anesthesia and has little relevance to the normal, unanesthetized condition.
Bar-Ilan
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A
Department of Pharmacology and Therapeutics, University of Florida College of Medicine, Gainesville.
Pessah
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D000287:Administration, Topical; D000768:Anesthesia, General; D000772:Anesthesia, Local; D000779:Anesthetics, Local; D000818:Animals; D001548:Benzalkonium Compounds / Q000494:pharmacology; D001574:Benzolamide / Q000494:pharmacology*; D001682:Biological Availability; D002257:Carbonic Anhydrase Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D004347:Drug Interactions; D005123:Eye / Q000187:drug effects* / Q000378:metabolism; D007429:Intraocular Pressure / Q000187:drug effects*; D008012:Lidocaine / Q000494:pharmacology; D008297:Male; D011430:Propoxycaine / Q000494:pharmacology; D011817:Rabbits; D013830:Thiadiazoles / Q000494:pharmacology*
D000779:Anesthetics, Local; D001548:Benzalkonium Compounds; D002257:Carbonic Anhydrase Inhibitors; D013830:Thiadiazoles; D008012:Lidocaine; C005717:proxymetacaine; D011430:Propoxycaine; D001574:Benzolamide