PubMed · 3567937
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J E Overall, D V Sheehan. 1986. Multivariate analysis of changes in panic frequency counts.. https://pubmed.ncbi.nlm.nih.gov/3567937/
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Previous studies have indicated that conventional description of drug/cyclodextrin complexes in aqueous solutions as inclusion complexes are not as unambiguous as one might think. It has been shown that in some cases drug/cyclodextrin complexes consist of a mixture of inclusion and non-inclusion complexes. Furthermore it has been shown that drug/cyclodextrin complexes can form aggregates containing up to couple of hundred complexes. In this present study beta-cyclodextrin (betaCD) solubilization of hydrocortisone is enhanced by including short-chain anionic and cationic species in the aqueous complexation medium. For example, maximum hydrocortisone solubility in pure aqueous betaCD solutions or suspensions is 2.2 mg/ml. Addition of 1% (w/v) sodium acetate to the complexation medium increases this value to 7.1 mg/ml (or over 220%). Further addition of 0.25% (w/v) hydroxypropyl methylcellulose to the medium increased the hydrocortisone solubility to over 9 mg/ml. Similar results were obtained when sodium salicylate or benzalkonium chloride were added to the complexation medium. It is also shown that cyclodextrin complexes of lipophilic compounds that have good affinity for the cyclodextrin cavity can be used to enhance cyclodextrin solubilization of drugs that have low affinity for the cavity. All these observations can be explained by formation of drug/cyclodextrin complex aggregates.
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OBJECTIVE: To evaluate use of clomipramine, alprazolam, and behavior modification for treatment of storm phobia in dogs. DESIGN: Prospective open clinical trial. ANIMALS: 40 dogs with storm phobia. PROCEDURE: Dogs received clomipramine at a dosage of 2 mg/kg (0.9 mg/lb), PO, every 12 hours for 3 months; then 1 mg/kg (0.45 mg/lb), PO, every 12 hours for 2 weeks; then 0.5 mg/kg (0.23 mg/lb), PO, every 12 hours for 2 weeks. Alprazolam was given at a dosage of 0.02 mg/kg (0.009 mg/lb), PO, as needed 1 hour before anticipated storms and every 4 hours as needed. Desensitization and counter-conditioning were conducted at home by the caregiver with an audio simulation of storm sounds that had induced a fear response during evaluation. RESULTS: 30 of the 32 dogs that completed the study had a degree of improvement, as measured by caregivers' global assessment. Two caregivers considered the storm phobia to be resolved. Panting, pacing, trembling, remaining near the caregiver, hiding, excessive salivation, destructiveness, excessive vocalization, self-trauma, and inappropriate elimination all decreased significantly during treatment. Improvement was greater during true storms (rain, thunder, and lightning) than during rain only. Response to audio simulation did not change during treatment. Four months after the study, improvement was maintained. CONCLUSIONS AND CLINICAL RELEVANCE: The combination of clomipramine, alprazolam, and behavior modification can be effective in decreasing or eliminating storm phobia. Improvement could not be evaluated by use of audio simulation of a storm.