Systemic bioavailability of ocularly applied 1% atropine eyedrops

Abstract

ABSTRACT.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 (AUC 0-≤) for 1-hyoscyamine was 1.862∫0.580 mg/L ¡ hr after intravenous, and 1.092∫0.381 ml/L ¡ hr after ocular administration (mean∫s.d, nΩ6), respectively. The mean bioavailability was 63.5∫28.6% (mean∫SD, nΩ6; min 19%, max 95%). Large interindividual differences characterized the absorption and elimination phases of 1-hyoscyamine kinetics. The terminal half-life (t 1 / 2 b) 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 association with the clinical use of atropine eyedrops.

Application of an enantioselective LC‐ESI MS/MS procedure to determine R‐ and S‐hyoscyamine following intravenous atropine administration in swine

“…Most of the PK studies published report on S-hyo or atropine in humans after administration by the ocular, [4] oral, [3,27] sublingual, [28] rectal, [29] inhalational, [14,16] i.m., . [12,17,20,[29][30][31][32][33][34] or i.v.…”

“…[1] S-hyo acts as an antagonist of muscarinic receptors (MR) thus inhibiting acetylcholine-mediated signal transduction. [2] Competitive MR antagonists are used clinically for pre-anesthesia medication, [3] ophthalmologic procedures [4] and the therapy of anticholinesterase poisoning. [2] Competitive MR antagonists are used clinically for pre-anesthesia medication, [3] ophthalmologic procedures [4] and the therapy of anticholinesterase poisoning.…”

The Influence of the Autonomic Nervous System on the Human Choroid

“…The time required for a drug to reach its plasma maximum concentration is equal to four to five times the half-life of the drug (Patil, 2004) and a total elimination time of a drug from the body (a washout period) is calculated as five-10 times the terminal elimination half-life (World Health Organization, 2004). Atropine has a plasma half-life of 2.5 ± 0.8 hours (Kaila et al, 1999) Therefore, it should not take longer than 16 hours, for atropine, to have its maximal effect on choroidal thickness, and another eight hours to be almost completely eliminated (96.9%-99.9% of the drug) from the body. Choroidal thickness should reach its pre-treatment levels by about 24 hours after initial administration of the drug.…”

“…To prevent contamination of a trial due to the residual action of a previously administered agent, a washout period of five to ten times the terminal elimination half-life of the drug was chosen (World Health Organization, 2004). Atropine used in the study has a terminal half-life of 2.5 ± 0.8 hours (Kaila et al, 1999). Therefore, choroidal thickness should reach its pretreatment levels by about 24 hours after initial administration of atropine and this period of time was implemented for part B of the experiment.…”

“…Atropine's terminal half-life is 2.5 ± 0.8 hours (Kaila et al, 1999). We used a period of 24 hours after administration of the drug to allow for 96.9% -99.9% elimination of the drug from the body.…”