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RESUMEN Fundamento: el dolor por cáncer sigue siendo difícil de tratar, especialmente cuando el paciente es resistente a los opioides. Cada vez más se buscan alternativas para contrarrestar y mejorar los síntomas provocados por la enfermedad. Uno de ellos es la ketamina, que actúa como antagonista de los receptores de N-metil-daspartato que se asocian como respuesta al dolor. Objetivo: evaluar la eficacia de la respuesta analgésica al dolor oncológico con la administración intranasal de ketamina como adyuvante en el tratamiento farmacológico. Métodos: investigación realizada en una clínica del dolor de Ecuador. Se realizó un estudio de cohorte con placebo, aleatorizado, a doble ciego. Se incluyeron 142 participantes. Se administraron dos tratamientos: ketamina y placebo intranasal, los cuales se usaron en combinación con morfina. Los participantes recibieron evaluaciones periódicas según la escala visual analógica del dolor, durante tres días consecutivos. Resultados: la edad media fue de 69,11 ± 9,77 años. El carcinoma que se presentó con mayor frecuencia fue el tumor de cabeza pancreático (44,37 %). Hubo diferencias significativas entre los tratamientos administrados, los aspectos clínicos y el dolor (p <0,05). Los pacientes que fueron tratados con ketamina tuvieron un efecto analgésico más relevante que los pacientes que recibieron el placebo. El principal efecto secundario fueron las náuseas (11,43 %). Conclusiones: los pacientes tratados con ketamina experimentaron mejor analgesia que el grupo control. La ketamina representa una opción para el dolor en quien no responde al tratamiento convencional con opioides. Los efectos adversos pueden ser un limitante para su aplicación en algunos pacientes.
ABSTRACT Background: cancer pain remains difficult to treat, especially when the patient is resistant to opioids. More and more alternatives are being sought to counteract and improve the symptoms caused by the disease. One of them is ketamine, which acts as an antagonist of NMDA receptors that are associated in response to pain. Objective: to evaluate the efficacy of the analgesic response to cancer pain with the intranasal administration of ketamine as an adjuvant in pharmacological treatment. Methods: research carried out in Ecuador pain clinic. A randomized, double-blind, placebo-controlled cohort study was conducted. 142 participants were included. Two treatments were administered: intranasal ketamine and placebo, which were used in combination with morphine. Participants received periodic visual analog pain scale assessments for three consecutive days. Results: the mean age was 69.11 ± 9.77 years. The pancreatic head tumor (44.37%) was the most frequently carcinoma. There were significant differences between administered treatments, clinical aspects and pain (p < 0.05). The patients who were treated with ketamine had a more relevant analgesic effect than the patients who received the placebo. The main side effect was nausea (11.43%). Conclusions: patients treated with ketamine experienced better analgesia than the control group. Ketamine represents an option for pain in those who do not respond to conventional opioid treatment. Adverse effects may limit its application in some patients.
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The objective of this study is to develop an in vitro screening method for nasal absorption of insulin. First, the adaptability of in situ rat nasal perfusion test for the study of insulin was investigated. It was found that insulin was liable to be absorbed on the silicone tube and the traditional method is not suitable. However, addition of 0.001% Labrasol into the perfusate can effectively solve this problem. A modified method suitable for in situ rat nasal perfusion of insulin was established with the addition of 0.001% Labrasol into the perfusate. Using the modified method, effect of pH and drug concentration on the absorption of insulin in the nasal cavity was further investigated. The results suggest that compared with pH 4.5 and pH 7.4, the drug absorption rate was the lowest at pH 6.0. The intranasal absorption mechanism of insulin may be passive diffusion.
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Objective To study the nasal mucosa absorption of paeonol ofXingbi microemulsion-based thermo-sensitive gel in rats; To evaluate the nasal mucosa absorption of medicine and the rationality of preparation form.Methods According to the nasal administration method, the blood medicine concentration of paeonol was determined at different time points.Results The nasal administration bioavailability of paeonol in Xingbi microemulsion-based thermo-sensitive gel was 78.68%, the plasma concentration reached the maximum (0.3404 μg/mL) after 3 min of administration, and the average residence time was 9.23 h. After reaching Cmax, The plasma concentration changed similar to intravenous administration of paeonol. The concentration data of paeonol in plasma was consistent with a two-compartment model, with a weight of 1.Conclusion Xingbi microemulsion-based thermo- sensitive gel has a higher bioavailability, and the preparation form was reasonable.
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This experiment focused on the effect of salvianolic acid B's nasal absorption characteristics in rats. In the study, HPLC determination of salvianolic acid B(SalB) in perfusion liquid was established to examine the SalB nasal irritation in different pH buffers and stability in nasal perfusion solution, and systematically study in vivo nasal absorption characteristics of SalB. Improved rats were adopted to establish the in situ nasal perfusion model to measure the release of total protein and lactate dehydrogenase in perfusion fluid, quantitatively evaluate the nasal irritation and the stability in perfusion liquid of pH 4.0, 5.0, 6.0 SalB phosphate buffer, compare the absorption of SalB in pH 5.0 buffer solution with low, medium and high concentrations (200, 400, 800 mg•L⁻¹). According to the results, nasal irritation: pH 4.0>pH 5.0>pH 6.0, RSD of pH 6.0 SalB buffer solution within 24 h was 3.1%, stability was poor. PH 5.0 SalB buffer solution had a smaller irritation and good stability. According to the nose perfusion test in rats, the nasal absorption of SalB fitted the first-order process and could be considered as passive absorption based on concentration gradient. SalB buffer solution of pH 5.0 had also a small nasal irritation and good stability, with a good absorption in rat nasal perfusion test, which therefore had a certain significance for the development of SalB nasal formulation.
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Objective: To compare the absorption characteristics of Luodian Borneolum and muscone after nasal unidirectional perfusion with different Xingnaojing preparations in rats. Methods: The nasal unidirectional perfusion model was used, the contents of Luodian Borneolum and muscone were determined by GC method, and the absorption of Luodian Borneolum and muscone in Xingnaojing Nasal Drop (XN) and Xingnaojing Microemulsion (XM) were compared. Results: The absorption rate constants (Ka) of Luodian Borneolum in XN and XM were (1.00 ± 0.02)and (0.76 ± 0.03) min-1, respectively, and the Ka values of muscone in XN and XM were (0.76 ± 0.02) and (0.58 ± 0.10) min-1, respectively. Conclusion: The absorption of Luodian Borneolum and muscone in XN are both faster than that in XM.
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OBJECTIVE: To study the relationship of oil/water partition coefficient of fluorouracil (5-FU) with its nasal absorption.METHODS: The octanol /water partition coefficient of 5-FU in Octanol-water were determine at different pH condition (4,6,7,8,10).In situ nasal recirculation method was used to estimate nasal absorption constant of 5-FU at different pH condition in rat.Regression analysis of obtained data was carried out.RESULTS: Oil/water partition coefficient and nasal absorption constant of 5-FU were increased as long as the value of pH with a positive correlation between them (r=0.983 8).CONCLUSION: There is a good linear relationship between oil/water partition coefficient and nasal absorption constant.
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AIM: To investigate the nasal absorption of ligustrazine and promotion action of synthetic borneol. METHODS: In situ nasal recirculation method was used to study the dose effect relationship of nasal absorption of ligustrazine and the effect of synthetic borneol on nasal absorption of ligustrazine in rats. RESULTS: When the concentrations of ligustrazine were 0.25 , 0.75 ,and 1.25 g?L -1 in circulation liquid, respectively, the corresponding values of the absorption rate constant k were 0.0195 , 0.0227 , and 0.0241 min -1 . However, when the concentrations were 2.5 and 5.0 g?L -1 in circulation liquid, the absorption rate constant k lowered with the concentration being added. CONCLUSION: Ligustrazine can be absorbed through the nasal mucous and synthetic borneol can promote the absorption.
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Aim The nasal absorption of furosemide and promotion action of l_menthol was examined. Methods In situ nasal recirculation methods was used to study the does_effect relationship of nasal absorption of furosemide and the effect of l_menthol on nasal absorption of furosemide in rats. Results When the concentration of furosemide in circulation liquid was respectively(4.66?0.33) ?(9.76?0.45) and (18.83?1.89) ?g?ml-1,the absorption rate constant k(min-1) of nasal in situ was correspondingly 0.0067?0.0011,0.0134?0.0024 and 0.0163?0.0037;and urine liquid appearing time was (73.33?1.53)?(52.67?7.02) and (47.00?4.58) min.But the larger the concentration of l_menthol, the little the absorption rate constant k. Conclusion Furosemide can be absorbed through the nasal mucous, and l_menthol can promote its absorption.