Systemic bioavailability of ocularly applied 1% atropine eyedrops.
OBJECTIVE
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.


CONCLUSIONS
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.
D000042:Absorption; D000287:Administration, Topical; D000328:Adult; D019540:Area Under Curve; D001285:Atropine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001682:Biological Availability; D018592:Cross-Over Studies; D005260:Female; D006207:Half-Life; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D009184:Mydriatics / Q000008:administration & dosage / Q000493:pharmacokinetics*; D009883:Ophthalmic Solutions / Q000008:administration & dosage / Q000493:pharmacokinetics; D011869:Radioligand Assay