Objective evaluation of the systemic effects of topical application of 1% atropine sulfate ophthalmic solution in healthy horses

Abstract

OBJECTIVE To determine the safety of topical administration of 1% atropine ophthalmic solution in healthy horses by objectively measuring gastrointestinal transit time. DESIGN Randomized, masked, controlled crossover study. ANIMALS 6 adult geldings. PROCEDURES Horses were randomly assigned (3/group) to first receive topical treatment of the left eye with 1% atropine or artificial tears solution; the right eye was left untreated. After 24 hours of treatment every 6 hours, 200 nontoxic beads were administered to each horse via nasogastric intubation and treatment frequency was decreased to every 12 hours for 4 more days. Pupillary light reflexes (PLRs), mydriasis, heart rate, fecal bead passage, abdominal girth measurements, auscultable gut sounds, fecal weight, and clinical signs of abdominal pain were monitored. Following a 4-week washout period, horses received the opposite treatment in the left eye and measurements were repeated. Serum atropine concentration (reflecting systemic absorption) was measured with an ELISA at various points after initial atropine administration. RESULTS No horse had subjective or objective evidence of colic or ileus at any monitoring point. Complete mydriasis of the left eye with absence of the PLR was identified in 5 horses within 6 hours and in all 6 horses within 12 hours after initial atropine administration. One horse had mydriasis with an absent PLR in the untreated eye by day 5 of atropine treatment. At no point was atropine detected in serum samples of any horse. CONCLUSIONS AND CLINICAL RELEVANCE Topical atropine application at clinically appropriate doses induced no evidence of ileus in healthy horses.

Topical ophthalmic atropine in horses, pharmacokinetics and effect on intestinal motility

“…However, none of the horses developed signs of colic and gut sounds were present at all auscultation points. After topical administration of 0.1 mL of 1% atropine ophthalmic solution (corresponding to the dose 1 mg atropine sulfate) every six hours, there was no significant difference in borborygmi-frequency compared to placebo (p = 0.17), which is consistent with an earlier report [17]. Moreover, neither the present study nor the study by Wehrman et al [17] detected any signs of abdominal pain.…”

“…The simulated increased plasma exposure due to accumulation may explain why atropine eye drops every 3 h was also associated with an effect on the gastrointestinal tract (in terms of gut motility) in part II of the present study. According to our data and simulations, when using eye drops, accumulation of atropine in plasma will be totally absent at a dosage interval of six hours, which in turn avoids adverse effects on the gastro-intestinal tract as shown in part II of the present study and the study by Wehrman et al [17].…”

“…These conflicting results suggest that the systemic atropine exposure after the less frequent dosing-protocol was not associated with a decrease in intestinal motility. This hypothesis was also supported by non-detectable plasma concentrations of atropine six hours after topical administration of 1 mg atropine sulfate, which was the first sampling time post administration [17]. However, the systemic disposition of atropine in horses following different modalities of atropine administration including topical eye medication is currently not reported in horses.…”

“…The onset of these adverse effects was between 11 h and 22 h after the first administered dose. In contrast, 1 mg of topical ophthalmic atropine sulfate every six hours did not affect intestinal transit time or borborygmi-frequency, nor cause signs of colic or abdominal discomfort in another study in six horses [17]. These conflicting results suggest that the systemic atropine exposure after the less frequent dosing-protocol was not associated with a decrease in intestinal motility.…”

Highlights of recent clinically relevant papers

“…The objective of this study by Rita Wehrman and colleagues in the USA was to determine the safety of topical administration of 1% atropine ophthalmic solution in healthy horses by objectively measuring gastrointestinal transit time .…”