Comparison of the effects of atropine in vivo and ex vivo (radioreceptor assay) after oral and intramuscular administration to man

Abstract

The effects of an oral dose of atropine (0.03 mg/kg body weight) and an IM (0.02 mg/kg) dose on the heart rate and salivary flow in seven healthy adult volunteers were compared to see whether the oral dose was sufficient to inhibit vagal reflexes of the heart. Atropine concentrations in plasma were determined by an M2-selective radioreceptor assay, and the in vitro occupancy of porcine cardiac M2-cholinoceptors was measured in parallel. In ligand-binding studies, atropine has been shown to have a comparable affinity for human and porcine cardiac M2-cholinoceptors (Ki 4.0 and 5.9, respectively). Slight changes in heart rate after oral administration were not significant. After IM administration, however, the heart rate increased significantly, by a maximum of 22 beats.min-1 after 45 min. The slight increase in heart rate after the oral dose corresponded to a receptor occupancy in vitro near the lower limit of detection, whereas the significant increase in heart rate after the IM dose corresponded to a receptor occupancy of up to 47%. The maximum reduction in salivary flow was similar after the oral and IM doses (84.3 and 87.5%, respectively). The almost complete inhibition of salivary flow could be explained by the lower vagal tone in the salivary glands compared with to the heart. The difference in the effect on heart rate was probably due to lower absorption of the oral dose. Thus, an oral dose greater than 0.03 mg atropine/kilogram body weight is required to compensate for low gastrointestinal absorption and to overcome the high vagal tone of the heart.

Scientific Opinion on Tropane alkaloids in food and feed

“…This rapid distribution of atropine to the tissues is consistent with the rapid onset of pharmacodynamic effects, which occur with the same time dependence as the plasma levels (i.e. stimulation of heart rate) (Kalser, 1971;Volz-Zang et al, 1995). Internal exposures to and effects of atropine appear to be greater in children and the elderly, albeit from different causes (i.e.…”

“…Seven healthy, non-smoking male volunteers (age ranging between 21 and 56 years, average body weight of 87.9 kg) were orally administered 30 g/kg b.w. atropine 17 (Volz-Zang et al, 1995). Heart rate, blood pressure and salivary secretion were monitored under resting conditions starting from 30 minutes before the treatment up to 3 hours after the treatment.…”

“…atropine 17 (Volz-Zang et al, 1995). Heart rate, blood pressure and salivary secretion were monitored under resting conditions starting from 30 minutes before the treatment up to 3 hours after the treatment.…”

Sublingual Atropine Drops for the Treatment of Pediatric Sialorrhea

“…Nonetheless, the family was reluctant to try any traditional treatments because of their associated adverse effects and the potential for interactions with the patient's multiple systemic medications. A trial of sublingual atropine was suggested on the presumption that it primarily exerts a local effect directly on the salivary glands, 45 which may result in minimal systemic absorption and adverse events. The individual and cumulative daily doses provided fell within a safe range based on the evidence for both oral and intravenous administration.…”

Systemic bioavailability of ocularly applied 1% atropine eyedrops

“…The cardiac effects of atropine are closely related to plasma 1-hyoscyamine concentrations (Kentala et al 1990). At plasma concentrations less than 0.5 ng/ ml l-hyoscyamine can slow heart rate, whereas at plasma concentrations exceeding 1.0 ng/ml l-hyoscyamine accelerates heart rate via vagolysis (Volz-Zang et al 1995;Wellstein & Pitschner 1988;Kanto et al 1990). In our subjects even the peak plasma l-hyoscyamine concentrations after ocular drug application were less than 0.4 ng/ml (Fig.…”