Psychiatry and Clinical Psychopharmacology
Original Article

Pharmacokinetics and Effects on Saliva Flow of Sublingual and Oral Atropine in Clozapine-Treated and Healthy Adults: An Interventional Cross-Over Study

1.

Sydney Medical School, Faculty of Medicine and Health, The University of Sydney, Missenden Mental Health Services, Royal Prince Alfred Hospital, NSW, Australia

2.

Senior Hospital Scientist, Department of Chemical Pathology, Royal Prince Alfred Hospital, NSW, Australia

3.

Sydney Pharmacy School, Faculty of Medicine and Health, The University of Sydney, NSW, Australia

4.

Sydney Medical School, Faculty of Medicine and Health, Concord Clinical School, The University of Sydney, NSW, Australia

Psychiatry and Clinical Psychopharmacology 2022; 32: 17-27
DOI: 10.5152/pcp.2022.21221
Read: 2101 Downloads: 240 Published: 01 March 2022

Background: Sublingual atropine is an effective treatment of clozapine-induced hypersalivation. This study aims to investigate the pharmacokinetics of atropine after sublingual and oral administration and study the dose effect of atropine on saliva secretion.

Methods: An interventional cross-over clinical trial where participants received 0.6 mg and 1.2 mg atropine sulfate sublingual solution and 0.6 mg oral tablet. Atropine plasma concentration was measured over 9 hours with validated LC-MS/MS method. Atropine effects on saliva secretion rate, visual acuity and accommodation, and vital signs were assessed.

Results: Four clozapine-treated and three healthy participants were enrolled in the study. The area under the atropine plasma concentration-time curve (AUC0-∞) was highest after the 1.2 mg sublingual solution administration in comparison with 0.6 mg tablet or sublingual solution (8.58±1.66 µg.L-1.h vs. 4.65±1.29 vs. 2.98±0.73 µg.L-1.h, respectively). The Cmax for the 0.6 mg and 1.2 mg sublingual solutions was 1.11±0.99 and 1.76±0.62 µg.L-1, and tmax was 2.18±0.59 and 1.9±0.71 h, respectively. In comparison with the 0.6 mg sublingual solution dose, the saliva secretion reduction was larger after the oral tablet administration (-40% (-59, -22%) vs. -69% (-80, -57)) and largest after the 1.2 mg sublingual solution administration (-79% (-93,-64)).

Conclusion: Both the sublingual and oral atropine are effective in reducing the saliva secretion however at a lower plasma concentration after sublingual administration, with a dose-dependent effect. Both have significantly reduced the blood pressure and pulse rate over 3 hours without significant changes in vision. No major safety concerns were reported.

Cite this article as: Mubaslat O, Fitzpatrick M, McLachlan AJ, Lambert T. Pharmacokinetics and effects on saliva flow of sublingual and oral atropine in Clozapine-treated and healthy adults: An interventional cross-over study. Psychiatr Clin Psychopharmacol. 2022;32(1):17-27.

Files
EISSN 2475-0581