Respiratory and cardiovascular effects of WP-934 in guinea pigs.
WP-934 is a newly developed reversible thermo-setting in situ gelling ophthalmic solution containing timolol. We investigated the effects of WP-934 on the respiratory and cardiovascular systems in guinea pigs and compared them with those of the conventional ophthalmic solution of timolol. At 30 min after instillation of timolol 0.5%, the airway responsiveness to histamine was 4 times higher, and that to acetylcholine was 2.5 times higher, than that before instillation. At 30 min after instillation of WP-934 0.5%, in contrast, the increase in responsiveness to each drug was about half that seen with the conventional solution. Topical instillation of timolol 0.5% weakened the effects of salbutamol and aminophylline on bronchodilatation, while that of WP-934 0.5% had no effect on aminophylline-induced bronchodilatation and a weaker effect on salbutamol-induced bronchodilatation. Topical instillation of timolol 0.5% and WP-934 0.5% failed to show a significant effect on blood pressure but caused a 10 to 20% decrease in heart rate for at least 120 min after instillation. WP-934 appears to have less respiratory adverse effects than timolol, mainly due to its longer retention on the ocular surface and a consequent decrease in systemic absorption.
Hashimoto
T
T
Sagami Research Laboratories, Wakamoto Pharmaceutical Co., Ltd., Tokyo, Japan. hashi@wakamoto-pharm.Co.jp
Toyoda
Y
Y
Taniguchi
T
T
Kitazawa
Y
Y
D000109:Acetylcholine / Q000494:pharmacology; D000287:Administration, Topical; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000420:Albuterol / Q000494:pharmacology; D000628:Aminophylline / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D016084:Bronchoconstriction / Q000187:drug effects; D002319:Cardiovascular System / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005782:Gels; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects; D006632:Histamine / Q000494:pharmacology; D008297:Male; D009883:Ophthalmic Solutions; D012137:Respiratory System / Q000187:drug effects*; D013999:Timolol / Q000494:pharmacology*
D000319:Adrenergic beta-Antagonists; D005782:Gels; D009883:Ophthalmic Solutions; D000628:Aminophylline; D013999:Timolol; D006632:Histamine; D000109:Acetylcholine; D000420:Albuterol