Systemic bioavailability of ocularly applied 1% atropine eyedrops

Purpose: To investigate the pharmacological basis of systemic effects of at ropine 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 ei ther intravenously or ocularly to six healthy volunteers, The plasma concen trations of the biologically active atropine enantiomer, 1-hyoscyamine, wer e determined using a muscarinic cholinoceptor binding assay. Results: The mean area under the curve from zero to infinitum (AUC(0-)(infi nity)) for 1-hyoscyamine was 1.862+/-0.580 mu g/L.hr after intravenous, and 1.092+/-0.381 mu l/L.hr after ocular administration (mean+/-s.d, n=6), res pectively. The mean bioavailability was 63.5+/-28.6% (mean+/-SD, n=6; min 1 9%, max 95%), Large interindividual differences characterized the absorptio n and elimination phases of I-hyoscyamine kinetics. The terminal half-life (t(1)/(2)beta) of 1-hyoscyamine in plasma was not affected by the route of drug administration. Conclusion: The systemic bioevailability of 1-hyoscyamine was considerable and may explain the systemic anticholinergic side effects reported in assoc iation with the clinical use of atropine eyedrops.