The Guinea Pig Blinking Test: a comparison with human responses.
The Guinea Pig Blinking Test (2) was presented as a model for the selection and development of comfortable ocular formulations. This study compares human nociceptive responses and the blinking response of the guinea pig to different concentrations of a topically applied ophthalmic drug, sulfacetamide. The number of human subjects noting pain upon instillation of various concentrations of sulfacetamide (3) was compared to the blinking responses of guinea pigs treated with 2.5%-17.5% sulfacetamide. The number of blinks was counted over a period of 5 minutes following (1) saline (0.9% NaCl), and (2) 30-60 minutes later a test solution. A Blinking Index (B.I.) = blinks drug/blinks saline was calculated for each animal. The dose/response curves of both humans and guinea pigs were almost identical, showing a threshold at 5% sulfacetamide, followed by a linear increase, reaching a maximum at 12.5%-15% sulfacetamide. A 2.5% solution that elicited pain in 10% of human subjects yielded a B.I. = 1.04 +/- 0.05, whereas a 12.5% solution that elicited pain in 95% of human subjects yielded a B.I. = 1.61 +/- 0.13 (mean +/- S.E., n = 10, P < 0.05). The strong linear relationship between the guinea pig blinking response and the human perception of pain, following identical treatment with a topical ophthalmic drug, demonstrates that this animal test can be useful in predicting the degree of ocular discomfort of human subjects.
Bar-Ilan
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Pharmos, Ltd., Kiryat Weizmann, Rehovot, Israel.
D000322:Adrenergic Agonists; D000818:Animals; D015784:Betaxolol / Q000494:pharmacology; D001767:Blinking / Q000187:drug effects*; D004837:Epinephrine / Q000031:analogs & derivatives / Q000494:pharmacology; D006168:Guinea Pigs; D006801:Humans; D008297:Male; D009883:Ophthalmic Solutions / Q000494:pharmacology; D009994:Osmolar Concentration; D013409:Sulfacetamide / Q000494:pharmacology*
D000322:Adrenergic Agonists; D009883:Ophthalmic Solutions; D013409:Sulfacetamide; C015173:dipivefrin; D015784:Betaxolol; D004837:Epinephrine