Systemic Bioavailability of Sublingual Atropine Ophthalmic Solution: a Phase I Study in Healthy Volunteers with Implications for Use as a Contingency Medical Countermeasure

Schwartz, Michael D.; Raulli, Robert; Laney, Judith; Coley, W. B.; Walker, Robert; O'Rourke, Anna W; Raine, Kathryn; Horwith, Gary; Gao, Yonghong; Eisnor, Derek L; Lü, Di; Wolling, Brenda; David, Gloria L.; Johnson, Keli; Barry, William T.; Chang, Jamie; Jepson, Brett; Fein, Melanie

doi:10.1007/s13181-021-00873-0

Cited by 4 publications

(15 citation statements)

References 13 publications

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“…For i.v. administration of atropine, V d = 210 L 33 . For the oral gel, CL/F = 146.3 L/h, which is comparable to reported clearance values.…”

Section: Discussionsupporting

confidence: 81%

“…For sublingual administration of eye drops, the low dose V d = 423.7 L and high dose V d = 496.7 L. 32 For i.v. administration of atropine, V d = 210 L. 33 For the oral gel, CL/F = 146.3 L/h, which is comparable to reported clearance values. Schwartz et al 33 reports mean CL/F of 108 L/h and 125.9 L/h after 0.5 mg and 0.1 mg atropine sulfate ophthalmic administration sublingually, which is expected.…”

Section: Discussionsupporting

confidence: 80%

“…After dose normalization, the C max of the oral gel is 1.4 × 10 −6 mg/mL. Compared to the two sublingual doses of 1 mg and 0.5 mg, C max was 1.46 × 10 −6 and 1.47 × 10 −6 mg/mL after dose normalization, respectively 33 . The C max is lowest for the oral gel, albeit comparable to the sublingual doses.…”

Section: Resultsmentioning

confidence: 88%

“…Atropine PK has been evaluated orally, i.v., i.m., and sublingually, but never in the form of an oral gel 33–35,41,42 . The atropine oral gel has lower plasma concentrations of atropine than any other administration route.…”

Section: Discussionmentioning

confidence: 99%

“…The relative bioavailability ( F rel ) was calculated for atropine gel versus sublingual administration of atropine eye drops 33 using the equation provided in File S5. Using AUC to the last positive measurable concentration (AUC last ), F rel was calculated in comparison to data reported by Schwartz et al 33 . using NCA.…”

Section: Methodsmentioning

confidence: 99%

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Clinical pharmacokinetics of atropine oral gel formulation in healthy volunteers

Parrot,

Yathavan,

Averin

et al. 2024

Clinical Translational Sci

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Sialorrhea or drooling is a common problem in children and adults with neurodevelopmental disorders. It can negatively impact the quality of life due to its physical and psychological manifestations. Providers commonly prescribe atropine eye drops for topical administration to the oral mucosa, as an off‐label treatment to manage sialorrhea. However, the off‐label use of atropine eye drops can be associated with medication and dosing errors and systemic side effects. To address these limitations of treatment, we developed a mucoadhesive topical oral gel formulation of atropine as an alternative route to off‐label administration of atropine eye drops. In this clinical pharmacokinetic (PK) study, we evaluated the safety and PK of atropine gel (0.01% w/w) formulation after single‐dose administration to the oral mucosa in 10 healthy volunteers. The PK data showed that after topical administration to the oral mucosa, atropine followed a two‐compartment PK profile. The maximum plasma concentration and area under the curve extrapolated to infinite time were 0.14 ng/mL and 0.74 h·ng·mL−1, respectively. The absorption rate constant calculated by the compartmental analysis was 0.4 h−1. Safety parameters, such as heart rate, blood pressure, and oxygen saturation, did not significantly change before and after administration of the gel formulation, and no adverse events were observed in all participants who received atropine gel. These data indicate that atropine gel formulation has a satisfactory PK profile, is well‐tolerated at the dose studied, and can be further considered for clinical development as a drug product to treat sialorrhea.

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“…For i.v. administration of atropine, V d = 210 L 33 . For the oral gel, CL/F = 146.3 L/h, which is comparable to reported clearance values.…”

Section: Discussionsupporting

confidence: 81%

Section: Discussionsupporting

confidence: 80%

Section: Resultsmentioning

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 3 more Smart Citations

Clinical pharmacokinetics of atropine oral gel formulation in healthy volunteers

Parrot,

Yathavan,

Averin

et al. 2024

Clinical Translational Sci

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Novichok

Watson¹,

Whitledge²,

Chai³

2024

Encyclopedia of Toxicology

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Examining the Role of Sublingual Atropine for the Treatment of Sialorrhea in Patients with Neurodevelopmental Disabilities: A Retrospective Review

Petkus

Noritz

Glader

2023

JCM

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Sialorrhea is common in children with neurodevelopmental disabilities (NDD) and is reported in >40% of children with cerebral palsy (CP). It causes a range of complications, including significant respiratory morbidity. This single-center retrospective chart review aims to document sublingual atropine (SLA) utilization to guide further study in establishing its role in secretion management for children with NDD. A chart review was completed for patients with NDD ≤ 22 years of age treated with SLA at a free-standing children’s hospital between 1 January 2016 and 1 June 2021. Descriptive statistics were generated to summarize findings. In total, 190 patients were identified, of which 178 met inclusion criteria. The average starting dose for SLA was 1.5 mg/day, or 0.09 mg/kg/day when adjusted for patient weight. Eighty-nine (50%) patients were prescribed SLA first line for secretion management while 85 (48%) patients tried glycopyrrolate prior to SLA. SLA was used after salivary Botox, ablation, and/or surgery in 16 (9%) patients. This study investigates SLA as a potential pharmacologic agent to treat sialorrhea in children with NDD. We identify a range of prescribing patterns regarding dosing, schedule, and place in therapy, highlighting the need for further evidence to support and guide its safe and efficacious use.

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Systemic Bioavailability of Sublingual Atropine Ophthalmic Solution: a Phase I Study in Healthy Volunteers with Implications for Use as a Contingency Medical Countermeasure

Cited by 4 publications

References 13 publications

Clinical pharmacokinetics of atropine oral gel formulation in healthy volunteers

Clinical pharmacokinetics of atropine oral gel formulation in healthy volunteers

Novichok

Examining the Role of Sublingual Atropine for the Treatment of Sialorrhea in Patients with Neurodevelopmental Disabilities: A Retrospective Review

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