Wenzhu Li, Fang Zhao, Jiayu Yang, Jianyang Pan, H. Qu
OBJECTIVES This study aimed to establish a rapid and comprehensive method for quantitative determination of complex ingredients in Traditional Chinese Medicine injections. METHODS A 1H quantitative nuclear magnetic resonance method was developed to simultaneously quantify comprehensive chemical components in Danshen Injection. Multivariate statistical analysis technique was applied to quality evaluation of multiple batches of Danshen injection. KEY FINDINGS A complete signal attribution to the 1H nuclear magnetic resonance spectrum of Danshen injection was developed and performed for the first time. A total of 32 chemical components were identified from Danshen Injection. Among them, 20 were quantified simultaneously, accounting for up to 80% (w/w) of the total solids and 95% (w/w) of total organic matter, representing success compared to the previous studies. The developed method was further applied to analyze 13 batches of Danshen Injection from three manufacturers to make a realistic analysis. CONCLUSION It was found that the comprehensive chemical information provides an adequate characterization for quality profiles among different commercial batches of Danshen Injection. The developed method further offered a guarantee for improving the consistency and safety of Traditional Chinese Medicine injections.
{"title":"Development of a comprehensive method based on quantitative 1 H NMR for quality evaluation of Traditional Chinese Medicine injection: a case study of Danshen Injection.","authors":"Wenzhu Li, Fang Zhao, Jiayu Yang, Jianyang Pan, H. Qu","doi":"10.1093/jpp/rgac034","DOIUrl":"https://doi.org/10.1093/jpp/rgac034","url":null,"abstract":"OBJECTIVES\u0000This study aimed to establish a rapid and comprehensive method for quantitative determination of complex ingredients in Traditional Chinese Medicine injections.\u0000\u0000\u0000METHODS\u0000A 1H quantitative nuclear magnetic resonance method was developed to simultaneously quantify comprehensive chemical components in Danshen Injection. Multivariate statistical analysis technique was applied to quality evaluation of multiple batches of Danshen injection.\u0000\u0000\u0000KEY FINDINGS\u0000A complete signal attribution to the 1H nuclear magnetic resonance spectrum of Danshen injection was developed and performed for the first time. A total of 32 chemical components were identified from Danshen Injection. Among them, 20 were quantified simultaneously, accounting for up to 80% (w/w) of the total solids and 95% (w/w) of total organic matter, representing success compared to the previous studies. The developed method was further applied to analyze 13 batches of Danshen Injection from three manufacturers to make a realistic analysis.\u0000\u0000\u0000CONCLUSION\u0000It was found that the comprehensive chemical information provides an adequate characterization for quality profiles among different commercial batches of Danshen Injection. The developed method further offered a guarantee for improving the consistency and safety of Traditional Chinese Medicine injections.","PeriodicalId":366080,"journal":{"name":"The Journal of pharmacy and pharmacology","volume":"46 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134060863","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gang Liu, Laijie Wang, Muhadasi Tuerxunyiming, Jin Xu, Zaifeng Wu, Wei Wang, Hongyu Liu, Lin Lin, Qingbai Liu
OBJECTIVES Osteoarthritis (OA) is a joint degenerative disease that commonly occurs in older people and affect the quality of life. Triptolide (TPL), a compound derived from Tripterygium wilfordii, has been shown to exhibit anti-inflammatory properties. Here, we investigated the therapeutic effect of TPL on the experimental OA as well as the underlying molecular mechanisms. METHODS OA models were established using monosodium iodoacetate (MIA) or surgery. The arthritis score and paw withdrawal threshold value of knees were used to evaluate the degree of arthritis. The level and expression of proinflammatory cytokines were evaluated by quantitative real-time PCR and ELISA kits. KEY FINDINGS In surgery and MIA-induced OA rats, TPL alleviated arthritis symptoms and reduced inflammatory cytokine production in serum. In primary chondrocytes, TPL dose-dependently reversed lipopolysaccharide (LPS)-induced cell proliferation. Moreover, LPS-induced cell apoptosis and the expressions of proinflammatory cytokines interleukin-(IL-)6, IL-8, IL-1β, IL-12, tumour necrosis factor-α (TNF-α) and interferon-gamma (INF-γ) were also attenuated by TPL. Mechanistically, the therapeutic effects of TPL on OA were effective by dampening nuclear factor kappa B (NF-κB) activity leading to reduced proinflammatory cytokines production and inflammatory response. CONCLUSIONS TPL acts as an effective therapeutic drug for OA by mediating NF-κB signalling, thereby leading to the reduced proinflammatory cytokines production and inflammatory response.
{"title":"Triptolide ameliorates osteoarthritis by regulating nuclear factor kappa B-mediated inflammatory response.","authors":"Gang Liu, Laijie Wang, Muhadasi Tuerxunyiming, Jin Xu, Zaifeng Wu, Wei Wang, Hongyu Liu, Lin Lin, Qingbai Liu","doi":"10.1093/jpp/rgab182","DOIUrl":"https://doi.org/10.1093/jpp/rgab182","url":null,"abstract":"OBJECTIVES\u0000Osteoarthritis (OA) is a joint degenerative disease that commonly occurs in older people and affect the quality of life. Triptolide (TPL), a compound derived from Tripterygium wilfordii, has been shown to exhibit anti-inflammatory properties. Here, we investigated the therapeutic effect of TPL on the experimental OA as well as the underlying molecular mechanisms.\u0000\u0000\u0000METHODS\u0000OA models were established using monosodium iodoacetate (MIA) or surgery. The arthritis score and paw withdrawal threshold value of knees were used to evaluate the degree of arthritis. The level and expression of proinflammatory cytokines were evaluated by quantitative real-time PCR and ELISA kits.\u0000\u0000\u0000KEY FINDINGS\u0000In surgery and MIA-induced OA rats, TPL alleviated arthritis symptoms and reduced inflammatory cytokine production in serum. In primary chondrocytes, TPL dose-dependently reversed lipopolysaccharide (LPS)-induced cell proliferation. Moreover, LPS-induced cell apoptosis and the expressions of proinflammatory cytokines interleukin-(IL-)6, IL-8, IL-1β, IL-12, tumour necrosis factor-α (TNF-α) and interferon-gamma (INF-γ) were also attenuated by TPL. Mechanistically, the therapeutic effects of TPL on OA were effective by dampening nuclear factor kappa B (NF-κB) activity leading to reduced proinflammatory cytokines production and inflammatory response.\u0000\u0000\u0000CONCLUSIONS\u0000TPL acts as an effective therapeutic drug for OA by mediating NF-κB signalling, thereby leading to the reduced proinflammatory cytokines production and inflammatory response.","PeriodicalId":366080,"journal":{"name":"The Journal of pharmacy and pharmacology","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"130145620","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 1992-09-01DOI: 10.1016/1043-6618(92)91038-I
G. Trimarchi, C. Imperatore, F. Arcadi, A. Saija, A. De Sarro, G. De Sarro, G. Costa
{"title":"Increased cardiovascular responsiveness to central cholinergic stimulation in the genetically epilepsy-prone rat.","authors":"G. Trimarchi, C. Imperatore, F. Arcadi, A. Saija, A. De Sarro, G. De Sarro, G. Costa","doi":"10.1016/1043-6618(92)91038-I","DOIUrl":"https://doi.org/10.1016/1043-6618(92)91038-I","url":null,"abstract":"","PeriodicalId":366080,"journal":{"name":"The Journal of pharmacy and pharmacology","volume":"2 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"1992-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"128465388","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 1992-05-01DOI: 10.1016/1043-6618(92)90432-B
F. Buffoni, G. Banchelli, S. Cambi, G. Ignesti, R. Pirisino, L. Raimondi, G. Vannelli
{"title":"Skin wound healing: some biochemical parameters in guinea-pig.","authors":"F. Buffoni, G. Banchelli, S. Cambi, G. Ignesti, R. Pirisino, L. Raimondi, G. Vannelli","doi":"10.1016/1043-6618(92)90432-B","DOIUrl":"https://doi.org/10.1016/1043-6618(92)90432-B","url":null,"abstract":"","PeriodicalId":366080,"journal":{"name":"The Journal of pharmacy and pharmacology","volume":"20 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"1992-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"117059026","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 1989-06-01DOI: 10.1097/00132586-198906000-00053
P. Soares-da-Silva, M. Caramona
Methylene blue (3, 10 and 30 microM) increased the spontaneous outflow of endogenous dopamine and noradrenaline from sympathetic nerves supplying the dog mesenteric artery and drastically reduced the formation of endogenous dihydroxyphenylglycol (DOPEG). In addition, it decreased the accumulation of [3H]noradrenaline in the tissue, reduced the formation of [3H]DOPEG and [3H]normetanephrine, without altering the formation of [3H]dihydroxymandelic acid. In tissue homogenates of the same blood vessel, methylene blue 30 and 100 microM produced a significant reduction in the deamination of 5-hydroxytryptamine (5-HT), beta-phenylethylamine (beta-PEA) and tyramine. Methylene blue increased the accumulation of [3H]isoprenaline in the tissue, and markedly reduced the formation of [3H]O-methylisoprenaline ([3H]OMI). These results show that methylene blue alters the storage and disposition of the adrenergic transmitter.
亚甲基蓝(3、10和30微米)增加了犬肠系膜动脉交感神经的内源性多巴胺和去甲肾上腺素的自发流出，并显著减少内源性二羟基苯基乙二醇(DOPEG)的形成。此外，它减少了[3H]去甲肾上腺素在组织中的积累，减少了[3H]DOPEG和[3H]去甲肾上腺素的形成，但不改变[3H]二羟基杏仁酸的形成。在同一血管的组织匀浆中，亚甲基蓝30和100微米显著降低了5-羟色胺(5-HT)、β -苯乙胺(β - pea)和酪胺的脱胺作用。亚甲基蓝增加了[3H]异丙肾上腺素在组织中的积累，并显著减少了[3H] o -甲基异丙肾上腺素([3H]OMI)的形成。这些结果表明，亚甲蓝改变了肾上腺素能递质的储存和处置。
{"title":"Effects of methylene blue on the uptake, release and metabolism of noradrenaline in mesenteric arterial vessels.","authors":"P. Soares-da-Silva, M. Caramona","doi":"10.1097/00132586-198906000-00053","DOIUrl":"https://doi.org/10.1097/00132586-198906000-00053","url":null,"abstract":"Methylene blue (3, 10 and 30 microM) increased the spontaneous outflow of endogenous dopamine and noradrenaline from sympathetic nerves supplying the dog mesenteric artery and drastically reduced the formation of endogenous dihydroxyphenylglycol (DOPEG). In addition, it decreased the accumulation of [3H]noradrenaline in the tissue, reduced the formation of [3H]DOPEG and [3H]normetanephrine, without altering the formation of [3H]dihydroxymandelic acid. In tissue homogenates of the same blood vessel, methylene blue 30 and 100 microM produced a significant reduction in the deamination of 5-hydroxytryptamine (5-HT), beta-phenylethylamine (beta-PEA) and tyramine. Methylene blue increased the accumulation of [3H]isoprenaline in the tissue, and markedly reduced the formation of [3H]O-methylisoprenaline ([3H]OMI). These results show that methylene blue alters the storage and disposition of the adrenergic transmitter.","PeriodicalId":366080,"journal":{"name":"The Journal of pharmacy and pharmacology","volume":"17 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"1989-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"128072521","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 1988-04-01DOI: 10.1097/00132586-198804000-00029
J. Walker, C. Shanks, C. Borton, K. Brown
Previous studies suggest that the muscles of the diaphragm are less sensitive to neuromuscular blocking agents than the limb muscles. However, this difference has not been characterized directly in terms of relaxant drug plasma concentrations. The pharmacodynamics of the non-depolarizing muscle relaxant alcuronium were therefore investigated in nine dogs using a constant-rate infusion regimen with simultaneous measurement of muscle paralysis in the limb and diaphragm. Maximum paralysis between 95 and 100% was achieved in both muscle groups, within approximately the same time interval. However, during onset of and offset of effect, the pharmacodynamic parameters ECp50 and ECp95 for the limb muscle were lower than in the diaphragm. From a pharmacodynamic effect model it was also predicted that Css(50) and Css(95) for the limb muscles are half those values for the diaphragm. Thus, the diaphragm is less sensitive to the action of alcuronium than are limb muscles. The half-time for equilibration of alcuronium between plasma and the effect site was two-fold lower for the diaphragm, and the rate of recovery from paralysis in diaphragmatic muscles was twice that observed in limb muscles. Collectively, these data suggest that there is a greater margin of safety in the diaphragmatic muscles and that the response of the peripheral limb muscles to nerve stimulation provides only a conservative index of recovery from competitive neuromuscular block in the diaphragmatic muscles.
{"title":"Alcuronium pharmacodynamics in dogs: effect-concentration relationships in the diaphragmatic and limb muscles.","authors":"J. Walker, C. Shanks, C. Borton, K. Brown","doi":"10.1097/00132586-198804000-00029","DOIUrl":"https://doi.org/10.1097/00132586-198804000-00029","url":null,"abstract":"Previous studies suggest that the muscles of the diaphragm are less sensitive to neuromuscular blocking agents than the limb muscles. However, this difference has not been characterized directly in terms of relaxant drug plasma concentrations. The pharmacodynamics of the non-depolarizing muscle relaxant alcuronium were therefore investigated in nine dogs using a constant-rate infusion regimen with simultaneous measurement of muscle paralysis in the limb and diaphragm. Maximum paralysis between 95 and 100% was achieved in both muscle groups, within approximately the same time interval. However, during onset of and offset of effect, the pharmacodynamic parameters ECp50 and ECp95 for the limb muscle were lower than in the diaphragm. From a pharmacodynamic effect model it was also predicted that Css(50) and Css(95) for the limb muscles are half those values for the diaphragm. Thus, the diaphragm is less sensitive to the action of alcuronium than are limb muscles. The half-time for equilibration of alcuronium between plasma and the effect site was two-fold lower for the diaphragm, and the rate of recovery from paralysis in diaphragmatic muscles was twice that observed in limb muscles. Collectively, these data suggest that there is a greater margin of safety in the diaphragmatic muscles and that the response of the peripheral limb muscles to nerve stimulation provides only a conservative index of recovery from competitive neuromuscular block in the diaphragmatic muscles.","PeriodicalId":366080,"journal":{"name":"The Journal of pharmacy and pharmacology","volume":"19 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"1988-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"133658202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 1988-02-01DOI: 10.1097/00132586-198802000-00009
M. Andrews, C. Doro, J. Nolan, R. Whittaker
The effects of equimolar concentrations (3.0 X 10(-5) M) of succinylcholine (SCh) and succinylmonocholine (SMC) were studied in-vitro at 20 degrees C in rat extensor digitorum longus muscle (EDL) 0-147 days after common peroneal nerve section. Analysis of simultaneous measurements of K+ efflux (mmolL-1 g-1) and contracture tension (mN) to SCh showed that there was a rapid increase in the mean values of both parameters up to 22-28 days after denervation (7.7 mmolL-1 g-1, 36 mN). At the end of the period studied, the contracture response declined to 4.0 mN whilst the capacity for K+ efflux remained relatively high (4.8 mmolL-1 g-1) in comparison with normal contralateral EDL muscle (n = 82) K+ efflux measurements (0.62 mmolL-1 g-1). A significant correlation (r = 0.86, P less than or equal to 0.001) was found between SCh-induced K+ efflux and contracture tension 1-56 days following nerve section which indicated that the development of the contracture response and K+ efflux were concomitant during the period specified. The ratios of maximum contracture tension/K+ efflux in response to SCh and SMC, 18-22 days after denervation were similar, 4.9 and 5.9, respectively. Results indicated that the mode of action of each agent was similar in denervated rat skeletal muscle, and that they were equally potent in their hyperkalaemic potential. Results of comparative measurements of membrane depolarization and contracture tension in response to SCh and SMC showed that both agents produced quantitatively similar responses at 7 and 14 days after denervation.(ABSTRACT TRUNCATED AT 250 WORDS)
{"title":"Comparison of the mode of action of succinylcholine and succinylmonocholine on rat skeletal muscle after denervation.","authors":"M. Andrews, C. Doro, J. Nolan, R. Whittaker","doi":"10.1097/00132586-198802000-00009","DOIUrl":"https://doi.org/10.1097/00132586-198802000-00009","url":null,"abstract":"The effects of equimolar concentrations (3.0 X 10(-5) M) of succinylcholine (SCh) and succinylmonocholine (SMC) were studied in-vitro at 20 degrees C in rat extensor digitorum longus muscle (EDL) 0-147 days after common peroneal nerve section. Analysis of simultaneous measurements of K+ efflux (mmolL-1 g-1) and contracture tension (mN) to SCh showed that there was a rapid increase in the mean values of both parameters up to 22-28 days after denervation (7.7 mmolL-1 g-1, 36 mN). At the end of the period studied, the contracture response declined to 4.0 mN whilst the capacity for K+ efflux remained relatively high (4.8 mmolL-1 g-1) in comparison with normal contralateral EDL muscle (n = 82) K+ efflux measurements (0.62 mmolL-1 g-1). A significant correlation (r = 0.86, P less than or equal to 0.001) was found between SCh-induced K+ efflux and contracture tension 1-56 days following nerve section which indicated that the development of the contracture response and K+ efflux were concomitant during the period specified. The ratios of maximum contracture tension/K+ efflux in response to SCh and SMC, 18-22 days after denervation were similar, 4.9 and 5.9, respectively. Results indicated that the mode of action of each agent was similar in denervated rat skeletal muscle, and that they were equally potent in their hyperkalaemic potential. Results of comparative measurements of membrane depolarization and contracture tension in response to SCh and SMC showed that both agents produced quantitatively similar responses at 7 and 14 days after denervation.(ABSTRACT TRUNCATED AT 250 WORDS)","PeriodicalId":366080,"journal":{"name":"The Journal of pharmacy and pharmacology","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"1988-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"130386003","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 1987-06-01DOI: 10.1097/00132586-198706000-00011
P. Cervat-Pisano, S. Dragna, C. Granthil, P. Coassola, J. Cano, G. Francois
Midazolam and 1-hydroxymidazolam plasma concentrations have been monitored and pharmacokinetic parameters of midazolam estimated during anaesthesia induced and maintained by its repeated injection according to two protocols (3 X 0.3 mg kg-1 at 45 min intervals or an induction dose of 0.3 mg kg-1 with maintenance doses of 0.15 mg kg-1 at 30 min intervals). Minimum plasma concentrations of midazolam measured just before each injection were 258.8 +/- 108.4 ng ml-1 for the first protocol and 353.1 +/- 55.2 ng ml-1 for the second protocol; maximum midazolam concentrations, measured 5 min after the last administration, were 1103.1 +/- 237.9 ng ml-1 and 743.0 +/- 103.2 ng ml-1, respectively, suggesting that a continuous infusion of midazolam after a loading dose should be better than repeated injections at keeping the concentration close to the sedative level of 400 ng ml-1. The estimated pharmacokinetic parameters were similar to those already published, except for the beta elimination half-life of midazolam (3.24 +/- 0.90 h for protocol 1 and 3.34 +/- 1.47 h for protocol 2) which was slightly longer than that reported for single dose studies. The comparison of plasma determinations, obtained either by gas-liquid chromatography or by a radioreceptor assay technique, clearly showed that 1-hydroxymidazolam, even after repeated midazolam administration, was not present at a concentration sufficient to affect the overall pharmacological activity of the parent drug.
监测咪达唑仑和1-羟基咪达唑仑的血浆浓度，估计咪达唑仑在诱导麻醉期间的药代动力学参数，并根据两种方案(3 X 0.3 mg kg-1，间隔45分钟或0.3 mg kg-1诱导剂量，间隔30分钟，维持剂量为0.15 mg kg-1)反复注射。每次注射前测量的咪达唑仑最低血浆浓度为第一种方案为258.8 +/- 108.4 ng ml-1，第二种方案为353.1 +/- 55.2 ng ml-1;末次给药后5min测得咪达唑仑的最大浓度分别为1103.1 +/- 237.9 ng ml-1和743.0 +/- 103.2 ng ml-1，提示在负荷剂量后继续注射咪达唑仑，浓度接近400 ng ml-1的镇静水平，应优于重复注射。估计的药代动力学参数与已发表的相似，除了咪达唑仑的β消除半衰期(方案1为3.24 +/- 0.90 h，方案2为3.34 +/- 1.47 h)略长于单剂量研究报告。通过气液色谱法或放射受体测定技术获得的血浆测定结果的比较，清楚地表明，即使在咪达唑仑反复给药后，1-羟基咪达唑仑的浓度也不足以影响母体药物的整体药理活性。
{"title":"Plasma concentrations and pharmacokinetics of midazolam during anaesthesia.","authors":"P. Cervat-Pisano, S. Dragna, C. Granthil, P. Coassola, J. Cano, G. Francois","doi":"10.1097/00132586-198706000-00011","DOIUrl":"https://doi.org/10.1097/00132586-198706000-00011","url":null,"abstract":"Midazolam and 1-hydroxymidazolam plasma concentrations have been monitored and pharmacokinetic parameters of midazolam estimated during anaesthesia induced and maintained by its repeated injection according to two protocols (3 X 0.3 mg kg-1 at 45 min intervals or an induction dose of 0.3 mg kg-1 with maintenance doses of 0.15 mg kg-1 at 30 min intervals). Minimum plasma concentrations of midazolam measured just before each injection were 258.8 +/- 108.4 ng ml-1 for the first protocol and 353.1 +/- 55.2 ng ml-1 for the second protocol; maximum midazolam concentrations, measured 5 min after the last administration, were 1103.1 +/- 237.9 ng ml-1 and 743.0 +/- 103.2 ng ml-1, respectively, suggesting that a continuous infusion of midazolam after a loading dose should be better than repeated injections at keeping the concentration close to the sedative level of 400 ng ml-1. The estimated pharmacokinetic parameters were similar to those already published, except for the beta elimination half-life of midazolam (3.24 +/- 0.90 h for protocol 1 and 3.34 +/- 1.47 h for protocol 2) which was slightly longer than that reported for single dose studies. The comparison of plasma determinations, obtained either by gas-liquid chromatography or by a radioreceptor assay technique, clearly showed that 1-hydroxymidazolam, even after repeated midazolam administration, was not present at a concentration sufficient to affect the overall pharmacological activity of the parent drug.","PeriodicalId":366080,"journal":{"name":"The Journal of pharmacy and pharmacology","volume":"7 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"1987-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"125190293","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 1981-04-01DOI: 10.1097/00132586-198104000-00011
M. Roberts, P. Cossum, A. Galbraith, G. Boyd
The availability of nitroglycerin from solution infused from Viaflex plastic infusion bags or glass infusion bottles through Buretrol plastic giving sets has been examined. Each of the individual components of the infusion bag/giving set system (i.e. infusion bag, burette and infusion tubing) sorbed nitroglycerin to a significant extent. It was found that the event and rate of nitroglycerin disappearance from solutions stored in each of the components were in the rank order: tubing greater than burette greater than infusion bag. The disappearance kinetics of nitroglycerin from solutions stored in each component was more accurately described by a 'diffusion' model than by the 'two compartment kinetic' model reported previously. The dimensions of the components and the volume of solution used were determinants of the rate and extent of nitroglycerin disappearance. In simulated infusions of nitroglycerin through plastic infusion bag (or glass bottle)/giving set system the flow rate of solution through the plastic infusion tubing affected the concentration of nitroglycerin in the effluent and the extent of sorption by the components of the infusion delivery system. The loss of nitroglycerin in these studies could be accounted for solely by the sorption of nitroglycerin by the plastic components of the infusion bag/giving set system.
{"title":"The availability of nitroglycerin from parenteral solutions.","authors":"M. Roberts, P. Cossum, A. Galbraith, G. Boyd","doi":"10.1097/00132586-198104000-00011","DOIUrl":"https://doi.org/10.1097/00132586-198104000-00011","url":null,"abstract":"The availability of nitroglycerin from solution infused from Viaflex plastic infusion bags or glass infusion bottles through Buretrol plastic giving sets has been examined. Each of the individual components of the infusion bag/giving set system (i.e. infusion bag, burette and infusion tubing) sorbed nitroglycerin to a significant extent. It was found that the event and rate of nitroglycerin disappearance from solutions stored in each of the components were in the rank order: tubing greater than burette greater than infusion bag. The disappearance kinetics of nitroglycerin from solutions stored in each component was more accurately described by a 'diffusion' model than by the 'two compartment kinetic' model reported previously. The dimensions of the components and the volume of solution used were determinants of the rate and extent of nitroglycerin disappearance. In simulated infusions of nitroglycerin through plastic infusion bag (or glass bottle)/giving set system the flow rate of solution through the plastic infusion tubing affected the concentration of nitroglycerin in the effluent and the extent of sorption by the components of the infusion delivery system. The loss of nitroglycerin in these studies could be accounted for solely by the sorption of nitroglycerin by the plastic components of the infusion bag/giving set system.","PeriodicalId":366080,"journal":{"name":"The Journal of pharmacy and pharmacology","volume":"10 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"1981-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"123852024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 1976-08-01DOI: 10.1097/00132586-197608000-00020
A. Ivankovich, D. J. Miletich, R. Albrecht, B. Zahed
The effects of pancuronium bromide infusion on the uptake and release of [14C] noradrenaline (14C-NA) by the isolated, perfused rat heart and on the chronotropic and inotropic activity of the isolated heart were evaluated. Hearts were removed from animals under light ether anaesthesia, transferred to a modified Langendorff perfusing apparatus and perfused with Krebs-Ringer bicarbonate solution at a rate of 5 ml min-1. The effect of pancuronium on the uptake of noradrenaline was determined by perfusing hearts for 5 min with perfusate containing various concentrations of pancuronium and 200 ng ml-1 of 14C-NA. After 5 min pancuronium-treated hearts contained less 14C-NA. The degree of reduced uptake increased with increasing concentrations of pancuronium. In addition, the combination of pancuronium perfusion and electrical stimulation (15 mA for 10 ms at 4 Hz) blocked the 50 min uptake of 14C-NA by the heart to a greater degree than either factor separately. The release of noradrenaline was determined after perfusing hearts with 14C-NA followed by perfusion with solution containing pancuronium but no 14C-NA for 1 h. Pancuronium infusion did not significantly alter the release of 14C-NA from the heart after 1 h of perfusion. The infusion of pancuronium caused a reduction in both the rate and strength of myocardial contraction of the isolated heart which was reversed by perfusion with perfusate free of pancuronium. Following perfusion with pancurnium the rate and strength of contraction of the heart was seen to "rebound" above pre-pancuronium values for a short period. The rebound of myocardial rate and contraction may have been due to the presence of myocardial noradrenaline previously blocked from reuptake by pancuronium since hearts removed from reserpinized animals did not demonstrate "rebound."
{"title":"The effect of pancuronium on myocardial contraction and catecholamine metabolism.","authors":"A. Ivankovich, D. J. Miletich, R. Albrecht, B. Zahed","doi":"10.1097/00132586-197608000-00020","DOIUrl":"https://doi.org/10.1097/00132586-197608000-00020","url":null,"abstract":"The effects of pancuronium bromide infusion on the uptake and release of [14C] noradrenaline (14C-NA) by the isolated, perfused rat heart and on the chronotropic and inotropic activity of the isolated heart were evaluated. Hearts were removed from animals under light ether anaesthesia, transferred to a modified Langendorff perfusing apparatus and perfused with Krebs-Ringer bicarbonate solution at a rate of 5 ml min-1. The effect of pancuronium on the uptake of noradrenaline was determined by perfusing hearts for 5 min with perfusate containing various concentrations of pancuronium and 200 ng ml-1 of 14C-NA. After 5 min pancuronium-treated hearts contained less 14C-NA. The degree of reduced uptake increased with increasing concentrations of pancuronium. In addition, the combination of pancuronium perfusion and electrical stimulation (15 mA for 10 ms at 4 Hz) blocked the 50 min uptake of 14C-NA by the heart to a greater degree than either factor separately. The release of noradrenaline was determined after perfusing hearts with 14C-NA followed by perfusion with solution containing pancuronium but no 14C-NA for 1 h. Pancuronium infusion did not significantly alter the release of 14C-NA from the heart after 1 h of perfusion. The infusion of pancuronium caused a reduction in both the rate and strength of myocardial contraction of the isolated heart which was reversed by perfusion with perfusate free of pancuronium. Following perfusion with pancurnium the rate and strength of contraction of the heart was seen to \"rebound\" above pre-pancuronium values for a short period. The rebound of myocardial rate and contraction may have been due to the presence of myocardial noradrenaline previously blocked from reuptake by pancuronium since hearts removed from reserpinized animals did not demonstrate \"rebound.\"","PeriodicalId":366080,"journal":{"name":"The Journal of pharmacy and pharmacology","volume":"27 11 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"1976-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"129476008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：