Systemic bioavailability of ocularly applied 1% atropine eyedrops

PURPOSE: To investigate the pharmacological basis of systemic effects of atropine eyedrops, we estimated the bioavailability of ophthalmic 1% atropine solution in healthy volunteers. METHODS: In a randomized crossover study we administered 0.3 mg atropine either intravenously or ocularly to six healthy volunteers. The plasma concentrations of the biologically active atropine enantiomer, 1-hyoscyamine, were determined using a muscarinic cholinoceptor binding assay. RESULTS: The mean area under the curve from zero to infinitum (AUC0-infinity) for 1-hyoscyamine was 1.862+/-0.580 microg/L x hr after intravenous, and 1.092+/-0.381 microl/L x hr after ocular administration (mean+/-sd, n=6), respectively. The mean bioavailability was 63.5+/-28.6% (mean+/-SD, n=6; min 19%, max 95%). Large interindividual differences characterized the absorption and elimination phases of 1-hyoscyamine kinetics. The terminal half-life (t1/2beta) of 1-hyoscyamine in plasma was not affected by the route of drug administration. CONCLUSION: The systemic bioavailability of 1-hyoscyamine was considerable and may explain the systemic anticholinergic side effects reported in association with the clinical use of atropine eyedrops.