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Introduction: The objective of this case series is to describe the clinical signs and outcome of cyclobenzaprine ingestion in two dogs treated with intralipid emulsion (ILE) and supportive care. Case or series summary: Two dogs presented for evaluation of cyclobenzaprine ingestion. A 4-year-old female spayed Rat Terrier (dog 1) presented within 4 h of ingestion of cyclobenzaprine (between 9.7 and 25.9 mg/kg). The dog experienced abnormal behavior, agitation, tremors, tachycardia, and hypertension. There were no significant clinicopathological abnormalities. The dog was treated with ILE, cyproheptadine, and activated charcoal. All clinical signs resolved after treatment. A 5-month-old female intact mixed-breed dog (dog 2) presented after ingestion of an unknown amount of cyclobenzaprine 2--3 h prior to presentation. The dog experienced dull mentation, tremors, loss of gag reflex, tachycardia, and hypertension. There were no significant clinicopathological abnormalities. Orogastric decontamination was performed via gastric lavage, and activated charcoal was given via orogastric tube, followed by ILE. All clinical signs resolved after therapeutic intervention. Discussion: This is the first report documenting clinical signs of cyclobenzaprine toxicity in two dogs followed by successful treatment with gastric emptying, ILE, and supportive care. [ABSTRACT FROM AUTHOR]

IntroductionThe objective of this case series is to describe the clinical signs and outcome of cyclobenzaprine ingestion in two dogs treated with intralipid emulsion (ILE) and supportive care.Case or series summaryTwo dogs presented for evaluation of cyclobenzaprine ingestion. A 4-year-old female spayed Rat Terrier (dog 1) presented within 4 h of ingestion of cyclobenzaprine (between 9.7 and 25.9 mg/kg). The dog experienced abnormal behavior, agitation, tremors, tachycardia, and hypertension. There were no significant clinicopathological abnormalities. The dog was treated with ILE, cyproheptadine, and activated charcoal. All clinical signs resolved after treatment. A 5-month-old female intact mixed-breed dog (dog 2) presented after ingestion of an unknown amount of cyclobenzaprine 2–3 h prior to presentation. The dog experienced dull mentation, tremors, loss of gag reflex, tachycardia, and hypertension. There were no significant clinicopathological abnormalities. Orogastric decontamination was performed via gastric lavage, and activated charcoal was given via orogastric tube, followed by ILE. All clinical signs resolved after therapeutic intervention.DiscussionThis is the first report documenting clinical signs of cyclobenzaprine toxicity in two dogs followed by successful treatment with gastric emptying, ILE, and supportive care.

In this work, a resonance Rayleigh scattering technique and a spectrofluorimetric technique were applied to the quantification of cyclobenzaprine through two validated methods. The suggested methods are based on a facile association complex formation between cyclobenzaprine and eosin Y reagent in the acidic medium. The resonance Rayleigh scattering method relied on the enhancement in the resonance Rayleigh scattering spectrum of eosin Y at 370 nm after the addition of cyclobenzaprine. On the other hand, the spectrofluorimetric quantification relied on the quenching effect of cyclobenzaprine on the fluorescence strength of the eosin Y reagent at 545 nm (excitation wavelength at 300 nm). The suggested methods were linear over the ranges of 0.07–1.75 μg/mL and 0.15–2.0 μg/mL with detection limit values of 0.023 μg/mL and 0.048 μg/mL for the resonance Rayleigh scattering method and the spectrofluorimetric method, respectively. All reaction conditions for cyclobenzaprine–eosin Y formation were experimentally evaluated and optimized. In addition, both methods were validated based on ICH rules. Furthermore, the developed methods were practically applied to the analysis of cyclobenzaprine in its commercial tablet dosage form with acceptable recoveries. Moreover, the content uniformity test of the commercial cyclobenzaprine tablets was successfully applied using the proposed spectroscopic methods based on USP rules.

Objective To examine the prevalence and duration of skeletal muscle relaxant (SMR) treatment among commercially insured adults in the United States. Methods We used the MarketScan Research Database to identify a cohort of adults 18 to 64 years who had ≥2-year continuous enrollment between 2005 and 2018. We estimated the prevalence of SMR treatment using a repeated cross-sectional design and derived treatment duration using the Kaplan-Meier method. Analyses were stratified by age group, sex, geographic region, individual SMR agent, and musculoskeletal disorder. Results 48.7 million individuals were included. Treatment prevalence ranged from 61.5 to 68.3 per 1,000. About one-third of users did not have a preceding musculoskeletal disorder diagnosis. Cyclobenzaprine was the dominant agent accounting for >50% of prescriptions. The considerable growth in the use of baclofen, tizanidine, and methocarbamol paralleled with a decline in carisoprodol and metaxalone use. The prevalence was highest in the South while lowest in the Northeast. The median treatment duration was 14 days with 4.0%, 1.9%, and 1.0% of individuals using SMRs for more than 90, 180, and 365 days, respectively. Compared with cyclobenzaprine, patients initiating baclofen, tizanidine, and carisoprodol had longer treatment duration. Conclusions SMRs are widely used in the United States. Their use slightly increased in recent years, but trends varied among individual agents, patient groups, and geographic regions. Despite limited evidence to support efficacy, a sizable number of U.S. adults used SMRs for long-term and off-label conditions. Further study is needed to understand determinants of treatment as well as outcomes associated with such use. [ABSTRACT FROM AUTHOR]

Suitable ex vivo models are required as predictive tools of oromucosal permeability between in vitro characterizations and in vivo studies in order to support the development of novel intraoral formulations. To counter a lack of clinical relevance and observed method heterogenicity, a standardized, controlled and physiologically relevant ex vivo permeation model was established. This model combined the Kerski diffusion cell, process automation, novel assays for tissue integrity and viability, and sensitive LC-MS/MS analysis. The study aimed to assess the effectiveness of the permeation model in the sublingual formulation development of cyclobenzaprine, a promising agent for the treatment of psychological disorders. A 4.68-fold enhancement was achieved through permeation model-led focused formulation development. Here, findings from the preformulation with regard to pH and microenvironment-modulating excipients proved supportive. Moreover, monitoring of drug metabolism during transmucosal permeation was incorporated into the model. In addition, it was feasible to assess the impact of dosage form alterations under stress conditions, with the detection of a 33.85% lower permeation due to salt disproportionation. Integrating the coherent processes of disintegration, dissolution, permeation, and metabolization within a physiological study design, the model enabled successful formulation development for cyclobenzaprine sublingual tablets and targeted development of patient-oriented drugs for the oral cavity.

Tricyclic fused-ring cyclobenzaprine (1) and amitriptyline (2) form 1:1 inclusion complexes with β-cyclodextrin (β-CD) in the solid state and in water solution. Rotating frame NOE experiments (ROESY) showed the same geometry of inclusion for both 1/β-CD and 2/β-CD complexes, with the aromatic ring system entering the cavity from the large rim of the cyclodextrin and the alkylammonium chain protruding out of the cavity and facing the secondary OH rim. These features matched those found in the molecular dynamics (MD) simulations in solution and in the solid state from single-crystal X-ray diffraction of 1/β-CD and 2/β-CD complexes. The latter complex was found in a single conformation in the solid state, whilst the MD simulations in explicit water reproduced the conformational transitions observed experimentally for the free molecule.