RESUMEN
The WHO biowaiver procedure for BCS Class II weak acids was evaluated by running two multisource IR ibuprofen drug products (Ibuprofen, 200 mg tablets, Tatchempharmpreparaty, Russia and Ibuprofen, 200 mg tablets, Biosintez, Russia) with current Marketing Authorizations (i.e. in vivo bioequivalent) through that procedure. Risks associated with excipients interaction and therapeutic index were considered to be not critical. In vitro dissolution kinetic studies were carried out according WHO Guidance (WHO Technical Report Series, No. 937, Annexes 7 and 8) using USP Apparatus II (paddle method) at 75 rpm. Dissolution profiles of test and reference ibuprofen tablets were considered equivalent in pH 4.5 using factors f(1) (13) and f(2) (72) and not equivalent in pH 6.8 (factor f(1) was 26 and f(2) was 24). Drug release of ibuprofen at pH 1.2 was negligible due to its weak acid properties. Therefore, two in vivo bioequivalent tablets were declared bioinequivalent by this procedure, indicating that procedure seems to be over-discriminatory.
RESUMEN
There were authentic distinctions between the groups of healthy volunteers and patients with a peptic ulcer disease in Cmax, Tmax, AUC(0-t), AUC(0-infinity), CIt, Vd of omeprazole and Cmax of esomeprazole (Nexium, AstraZeneca). When the pharmacokinetics of omeprazole and ezomeprazole were compared in both groups, there were authentic distinctions in Cmax, AU(0-t), AUC(0-infinity), CIt, T1/2. The patients who had taken omeprazole the time of hypoacide condition was much shorter than in other groups. Disintegration test modeling pHmax for pH oscillation with large amplitude, that is typical for ulcer disease, demonstrated a possibility of early partial release of omeprazole, its acid-depended degradation and reduction of its bioavailability.
Asunto(s)
Antiulcerosos/farmacocinética , Úlcera Duodenal/tratamiento farmacológico , Ácido Gástrico/metabolismo , Omeprazol/farmacocinética , Inhibidores de la Bomba de Protones/farmacocinética , Adulto , Antiulcerosos/administración & dosificación , Antiulcerosos/farmacología , Antiulcerosos/uso terapéutico , Disponibilidad Biológica , Úlcera Duodenal/metabolismo , Esomeprazol , Femenino , Determinación de la Acidez Gástrica , Humanos , Masculino , Omeprazol/administración & dosificación , Omeprazol/farmacología , Omeprazol/uso terapéutico , Inhibidores de la Bomba de Protones/administración & dosificación , Inhibidores de la Bomba de Protones/farmacología , Inhibidores de la Bomba de Protones/uso terapéutico , Factores de Tiempo , Distribución TisularRESUMEN
Concentrations of serotonin, beta-endorphine, myoglobin, basic myelin protein were measured in blood of patients with tunnel hand syndromes treated by actovegin or physiological solution pharmacopuncture and acupuncture to the same acupuncture points (AP). The above biochemical indices showed similar changes in pharmacopuncture with actovegin and the solution. These changes were different in acupuncture. This indicates specificity of AP stimulation by introduction of fluid, but not specificity of drug effects.
Asunto(s)
Síndrome del Túnel Carpiano/rehabilitación , Hemo/análogos & derivados , Síndromes de Compresión del Nervio Cubital/rehabilitación , Puntos de Acupuntura , Terapia por Acupuntura , Administración Tópica , Anticuerpos/sangre , Biomarcadores/sangre , Síndrome del Túnel Carpiano/sangre , Terapia Combinada , Hemo/administración & dosificación , Humanos , Proteína Básica de Mielina/inmunología , Factores de Tiempo , Síndromes de Compresión del Nervio Cubital/sangreAsunto(s)
Adaptación Fisiológica , Glándulas Suprarrenales/metabolismo , Catecolaminas/metabolismo , Encefalina Metionina/metabolismo , Infarto del Miocardio/metabolismo , Miocardio/metabolismo , Estrés Fisiológico/metabolismo , Animales , Estimulación Eléctrica , Atrios Cardíacos , Masculino , Ratas , Ratas WistarRESUMEN
Scalp acupuncture effects on blood biochemistry were investigated in 10 healthy volunteers. The results provided evidence for the absence of negative changes in function of neurohumoral systems of the body which may become factors of risk for patients with thrombogenic disturbances of cerebral circulation.
Asunto(s)
Terapia por Acupuntura , Sangre/metabolismo , Cuero Cabelludo , Puntos de Acupuntura , Terapia por Acupuntura/efectos adversos , Adulto , Femenino , Hemostasis , Humanos , Masculino , Factores de TiempoRESUMEN
The activity of antinociceptive mechanisms induced by footshock (FS) and morphine injection was studied in experiments on rats with bilateral destruction of group A10 neurones of the ventral tegmental area. The latent periods of the hot plate and tail flick pain reactions to FS and morphine increased significantly in the experimental and control groups as compared to the initial values. In morphine injection these indices were the same in the experimental and control groups. In FS the latent periods of the reaction were significantly greater in the experimental group. Thus, destruction of dopaminergic neurons of A10 nuclei intensifies the antinociceptive effects in FS but has no effect on the pain-relieving action of systemic morphine injection.
Asunto(s)
Analgesia , Morfina/farmacología , Neuronas/fisiología , Dolor/fisiopatología , Receptores Dopaminérgicos/fisiología , Tegmento Mesencefálico/fisiología , Animales , Estimulación Eléctrica , Neuronas/efectos de los fármacos , Ratas , Tiempo de Reacción/efectos de los fármacos , Tiempo de Reacción/fisiología , Receptores Dopaminérgicos/efectos de los fármacos , Tegmento Mesencefálico/efectos de los fármacos , Factores de TiempoRESUMEN
The dynamics of nociceptive reactions and character of 3H-naloxone binding to hypothalamus and midbrain synaptic membranes were studied in rats subjected to repeated cold swim stress (3 min. daily during 3, 5 and 15 days). It was shown that an increase of latencies of background nociceptive reactions (hot-plate and tail-flick tests) was accompanied by an ambiguous changes of kinetic parameters of 3H-naloxone binding in the studied brain structures. The results suggest that an increase of antinociceptive systems tone under repeated cold swim stress may be caused by a dynamic transformation of opiate u-receptor apparatus in various brain structures.
Asunto(s)
Frío/efectos adversos , Hipotálamo/metabolismo , Mesencéfalo/metabolismo , Naloxona/farmacocinética , Dolor/fisiopatología , Receptores Opioides/metabolismo , Animales , Ensayo de Unión Radioligante , Ratas , Tiempo de Reacción/fisiología , Receptores Opioides/análisis , Natación , Factores de Tiempo , TritioRESUMEN
The effect of amitriptyline (1.5 and 3 mg/kg intraperitoneally once a day for 1, 3, 5 days) on the latencies (L) of hot plate (HP) and tail flick (TF) at rest, after acupuncture (A) of bilateral Ho-ku and after inescapable foot-shock (IFS--1.0 mA, 50 Hz, 5 min) was studied in experiments on rats. It was shown that amitriptyline in the above doses, used in different periods of time, failed to effect L of HP and TF at rest. However, after A an increase of the analgesic effect was observed in the rats treated with 3 mg/kg of amitriptyline for 3 days. In the experiment with IFS an increase of the effect was pronounced in TF test 24 hours following administration of 1.5 and 3.0 mg/kg of amitriptyline.
Asunto(s)
Analgesia por Acupuntura , Amitriptilina/farmacología , Animales , RatasRESUMEN
The activity of antinociceptive mechanisms of auricular electroacupuncture (AEA) and footshock (FS) was studied on rats with bilaterally lesioned group A5 neurones. It was shown that the activity of the antinociceptive mechanisms triggered in experimental rats as compared to control rats. The data reveal the involvement of A5-nuclei in the antinociceptive mechanisms of AEA and FS.
Asunto(s)
Terapia por Acupuntura/métodos , Terapia por Estimulación Eléctrica/métodos , Neuronas/fisiología , Dolor/fisiopatología , Receptores Adrenérgicos/fisiología , Piel/fisiopatología , Estimulación Eléctrica Transcutánea del Nervio/métodos , Animales , Oído Externo , Estimulación Eléctrica/métodos , Electrodos Implantados , Ratas , Tiempo de Reacción/fisiología , Receptores de Catecolaminas , Factores de TiempoRESUMEN
The anxiolytic agents, buspirone and diazepam, increase the paw lick latency of rats in the hot plate test, the effect being dose-dependent and exceeding that of morphine. The action of buspirone was not accompanied by ataxic and sedative effects which were observed in rats on diazepam. Buspirone (up to 25 mg/kg) and diazepam (up to 5 mg/kg) neither change the tail flick latency nor potentiate the action of morphine on the test. A buspirone dose of 2 mg/kg administered to animals before foot shock, or the dose of 1.5 mg/kg before cold swimming stress, led to a significant increase in hot plate latency 1 min after stress as compared to the control. The effect of buspirone on the paw lick reaction in rats may be related to the activation of antinociceptive mechanisms and inhibition of an emotional-motivational component of the pain reaction.
Asunto(s)
Buspirona/farmacología , Nociceptores/efectos de los fármacos , Analgésicos/farmacología , Animales , Diazepam/farmacología , Relación Dosis-Respuesta a Droga , Combinación de Medicamentos , Masculino , Morfina/farmacología , Dimensión del Dolor , Ratas , Tiempo de Reacción , Estrés Fisiológico/fisiopatologíaRESUMEN
The activity of antinociceptive mechanisms in cold stress and under the effect of morphine was studied in experiments on rats subjected to bilateral destruction of group A5 neurons. In cold stress in rats of the experimental and control groups the latent periods (LP) of pain reactions of limb licking differed significantly, both in initial values and between the groups; in contrast, the LP of the tail-flick reaction did not differ significantly. Under the effect of morphine the pain reactions increased authentically as compared to the initial values both in the experimental and the control groups, but there were no significant differences between the groups. Thus, group A5 noradrenergic neurons have an effect on inhibiting some pain reaction components in cold stress, but are of no importance in the mechanisms of antinociceptive actions under the effect of morphine.
Asunto(s)
Analgesia , Catecolaminas/fisiología , Morfina/farmacología , Neuronas/fisiología , Animales , Frío , Neuronas/efectos de los fármacos , RatasRESUMEN
Changes in latencies (L) of nociceptive (NC) reactions of hot plate (HP) tail flick (TF) tests and dynamics of beta-endorphin (beta-ED) in hypothalamus and midbrain were studied in albino rats receiving 15 sessions of acupuncture (A) (20 min daily in bilateral Ho-Ku). It was shown that repeated A facilitated prolongation of LHP and LTF as compared to baseline and control levels. A decrease of the anti-NC systems capacity for activation in response to each A stimulation was observed. The dynamics of beta-endorphin in hypothalamus showed an opposite tendency as compared to that in midbrain. It is suggested that such a correlation of beta-ED activities in midbrain and hypothalamus might be one of the reasons for anti-NC mechanisms adaptation to A.
Asunto(s)
Terapia por Acupuntura , Endorfinas/análisis , Hipotálamo/análisis , Mesencéfalo/análisis , Dolor/fisiopatología , Animales , Endorfinas/fisiología , Dimensión del Dolor , RatasRESUMEN
Inhibition of the analgetic activity of systemic morphine and inescapable foot shock in certain moments of the experiment was shown on rats subjected to electrolytic destruction of nucleus raphe magnus. Cold swim stress increased analgesia as compared to the control animals. It is concluded that this formation of the brain is selectively and dynamically involved in mechanisms of various types of analgesia.
Asunto(s)
Analgesia , Frío/efectos adversos , Morfina , Dolor/fisiopatología , Núcleos del Rafe/fisiología , Estrés Fisiológico/fisiopatología , Animales , Estimulación Eléctrica , Masculino , Ratas , Tiempo de Reacción/fisiologíaRESUMEN
The activity of antinociceptive mechanisms induced by auricular electroacupuncture (AEA) and intraperitoneal injection of morphine (M) was studied on rats subjected to bilateral lesion of gigantocellular nuclei (GCN). It was shown that under AEA hot-plate (HP) and tail-flick (TF) latencies (L) significantly increased as compared to the baseline level. A comparison of L shows that HP and TF in the experimental group were significantly shorter than in the control group. After M injection the rats of both the experimental and control groups showed a significant increase of HP L and TF L as compared to the baseline level, but there was no difference in L between the groups. It is concluded that neurochemical systems of GCN are involved in the mechanism of antinociception elicited in AEA while the mechanisms of antinociceptive effect of M do not involve GCN.
Asunto(s)
Terapia por Acupuntura , Analgesia , Morfina/farmacología , Formación Reticular/fisiología , Animales , Oído Externo , Inyecciones Intraperitoneales , Morfina/administración & dosificación , Ratas , Formación Reticular/anatomía & histología , Formación Reticular/efectos de los fármacosAsunto(s)
Analgesia , Núcleo Hipotalámico Anterior/fisiología , Tubérculos Mamilares/fisiología , Animales , Núcleo Hipotalámico Anterior/efectos de los fármacos , Frío , Estimulación Eléctrica , Electrodos Implantados , Calor , Tubérculos Mamilares/efectos de los fármacos , Morfina , Dolor/fisiopatología , Ratas , Tiempo de Reacción/fisiología , Factores de TiempoRESUMEN
The activity of antinociceptive mechanisms during exposure to cold swim stress (CSS), inescapable foot shock (FS) and morphine administration (10 mg/kg) was studied in rats subjected to bilateral lesions of locus coeruleus (LC). It has been shown that under all types of stimulation the latent periods (LP) of nociceptive reactions of paw licking and tail flick were significantly increased, as compared to baseline level, thus suggesting suppression of the pain sensitivity. In rats subjected to CSS and morphine administration significantly shorter LP were revealed in the experimental group, compared to the control, which suggested partial inhibition of antinociceptive mechanisms activity after LC lesion. FS did not cause any differences in the experimental and control groups. It is concluded that LC lesions cannot completely inhibit the antinociceptive mechanisms activated by CSS and morphine injection. In FS monoamine mechanisms of LC do not seem to play an important role in the functioning of antinociceptive mechanisms.
Asunto(s)
Analgesia , Locus Coeruleus/fisiología , Analgésicos Opioides , Animales , Frío , Electrochoque , Morfina/farmacología , Nociceptores/fisiología , Ratas , Tiempo de Reacción , Estrés Fisiológico/fisiopatologíaRESUMEN
Anxiolytic agents, buspirone and diazepam, increase the paw lick latency of rats in hot plate test, the effect being dose-dependent and exceeding that of morphine. The action of buspirone was not accompanied by ataxic and sedative effects which were observed in rats on diazepam. Buspirone (up to 25 mg/kg) and diazepam (up to 5 mg/kg) neither change the tail flick latency nor potentiate the action of morphine in this test. The effect of buspirone on the paw lick reaction in rats may be related to the inhibition of emotional-motivation component of pain reaction.
Asunto(s)
Ansiolíticos/uso terapéutico , Morfina/uso terapéutico , Dolor/tratamiento farmacológico , Animales , Buspirona , Diazepam/uso terapéutico , Relación Dosis-Respuesta a Droga , Evaluación Preclínica de Medicamentos , Sinergismo Farmacológico , Masculino , Dolor/fisiopatología , Pirimidinas/uso terapéutico , Ratas , Tiempo de Reacción/efectos de los fármacos , Factores de TiempoRESUMEN
When studying cytoarchitectonics of the midbrain periaqueductal gray (PAG) in cat four areas were distinguished: medial, dorsal, lateral rostral and lateral caudal. They differ in size and distribution density of neurons.
Asunto(s)
Sustancia Gris Periacueductal/citología , Animales , Gatos , Recuento de CélulasRESUMEN
Stereotaxic fluid microinjections of horseradish peroxidase into different parts of the rostral and caudal periaqueductal grey (PAG) in cats have provided substantial retrograde evidence that the somatosensory cortex (I and II), frontal cortex, insular and cingular cortex are the principal sources of cortical-PAG projections. The somatosensory cortex II projects to all the regions of the rostral and caudal PAG. The frontal cortex projects to dorso-lateral quadrant of the PAG. The same projections were determined from insular and cingular cortex to PAG. The findings revealed a morphological substratum of corticofugal effects on PAG.