Journal of pharmacobio-dynamics最新文献_第6页

Neurotoxicity of panipenem/betamipron, a new carbapenem, in rabbits: correlation to concentration in central nervous system. 新型碳青霉烯类药物帕尼培南/倍他米酮对家兔的神经毒性:与中枢神经系统浓度的关系

Journal of pharmacobio-dynamics Pub Date : 1992-07-01 DOI: 10.1248/bpb1978.15.325

A Kurihara, M Hisaoka, N Mikuni, K Kamoshida

{"title":"Neurotoxicity of panipenem/betamipron, a new carbapenem, in rabbits: correlation to concentration in central nervous system.","authors":"A Kurihara, M Hisaoka, N Mikuni, K Kamoshida","doi":"10.1248/bpb1978.15.325","DOIUrl":"https://doi.org/10.1248/bpb1978.15.325","url":null,"abstract":"The neurotoxic potential of panipenem/betamipron (PAPM/BP), a new carbapenem antibiotic, was compared with that of imipenem/cilastatin (IPM/CS). The drug concentration in cerebrospinal fluid (CSF) at the onset of epileptogenic electroencephalographic (EEG)-activity and the drug distribution into the central nervous system (CNS) were evaluated. Epileptogenic reactions correlated well with drug levels in CSF, but not with drug levels in circulating plasma. The concentration of PAPM in CSF at the onset of epileptogenic EEG-activity was almost twice that of IPM, suggesting that neurotoxic activity of PAPM is about half that of IPM. In addition, in terms of incidence percent for the epileptogenic EEG-activity, PAPM/BP was found to be less toxic than IPM/CS within the dose of 1.0-1.2 g/kg. Concentrations of PAPM in CSF and brain extracellular fluid after PAPM/BP i.v. infusion were comparable with those of IPM after IPM/CS infusion, indicating the similar characteristics of distribution into the CNS for the two antibiotics. From these results of pharmacologic effects and drug distributions, it is suggested that the neurotoxicity of PAPM/BP is less than half that of IPM/CS.","PeriodicalId":16743,"journal":{"name":"Journal of pharmacobio-dynamics","volume":"15 7","pages":"325-32"},"PeriodicalIF":0.0,"publicationDate":"1992-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1248/bpb1978.15.325","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12619292","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}

引用次数: 9

Hypotensive effect of a phosphorus-containing novel angiotensin converting enzyme inhibitor, (S)-1-[6-amino-2[[hydroxy(4-phenylbutyl)phosphinyl] oxy]-1-oxohexyl]-L-proline (SQ 29,852) in conscious hypertensive dogs. 新型含磷血管紧张素转换酶抑制剂(S)-1-[6-氨基-2[[羟基(4-苯基丁基)膦基]氧]-1-氧己基]- l -脯氨酸(SQ 29,852)对有意识高血压犬的降压作用

Journal of pharmacobio-dynamics Pub Date : 1992-06-01 DOI: 10.1248/bpb1978.15.267

N Ohara, M Takizawa, S Yokota, N Ogawa, H Katsumura, H Ono

{"title":"Hypotensive effect of a phosphorus-containing novel angiotensin converting enzyme inhibitor, (S)-1-[6-amino-2[[hydroxy(4-phenylbutyl)phosphinyl] oxy]-1-oxohexyl]-L-proline (SQ 29,852) in conscious hypertensive dogs.","authors":"N Ohara, M Takizawa, S Yokota, N Ogawa, H Katsumura, H Ono","doi":"10.1248/bpb1978.15.267","DOIUrl":"https://doi.org/10.1248/bpb1978.15.267","url":null,"abstract":"The hypotensive efficacy of (S)-1-[6-amino-2[[hydroxy(4-phenylbutyl) phosphinyl]oxy]-1-oxohexyl]-L-proline (SQ 29,852), a phosphorus-containing novel angiotensin converting enzyme inhibitor (ACEI) was examined in conscious two-kidney, one-clip Goldblatt hypertensive dogs. The acute hypotensive effect of SQ 29 852 was compared with that of captopril or enalapril at 3 mg/kg, p.o., for each, and the potencies were ranked as follows, enalapril greater than SQ 29,852 greater than captopril. On the other hand, the hypotension caused by repetitive dosing with SQ 29,852 (3 mg/kg, p.o./d for 7 d followed by another 7-d treatment with 10 mg/kg, p.o./d) was somewhat more marked than that by enalapril at the same dosage. Blood urea nitrogen (BUN) increased in all the animals given enalapril, while that in all of the SQ 29,852-treated animals did not increase. These results indicate that SQ 29,852 is a potent, and long-lasting ACEI with a possible low incidence of side effects.","PeriodicalId":16743,"journal":{"name":"Journal of pharmacobio-dynamics","volume":"15 6","pages":"267-76"},"PeriodicalIF":0.0,"publicationDate":"1992-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1248/bpb1978.15.267","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12604514","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}

引用次数: 2

Activation of the complement system by (1----3)-beta-D-glucans having different degrees of branching and different ultrastructures. (1----3)- β - d -葡聚糖对补体系统的激活具有不同程度的分支和不同的超微结构。

Journal of pharmacobio-dynamics Pub Date : 1992-06-01 DOI: 10.1248/bpb1978.15.277

T Suzuki, N Ohno, K Saito, T Yadomae

{"title":"Activation of the complement system by (1----3)-beta-D-glucans having different degrees of branching and different ultrastructures.","authors":"T Suzuki, N Ohno, K Saito, T Yadomae","doi":"10.1248/bpb1978.15.277","DOIUrl":"https://doi.org/10.1248/bpb1978.15.277","url":null,"abstract":"Activation of the alternative (APC) and classical (CPC) pathways of complement by fungal (1----3)-beta-D-glucans having different degrees of branching (DB) and different conformations were examined by using human serum and plasma. The glucans used in this study were curdlan (no branch; 0/1), grifolan (one branch in every third main chain unit; 1/3), schizophyllan (1/3), SSG (1/2), and OL-2(2/3). Triple or single helix conformer of these glucans were prepared by heating at 150 degrees C or dissolution in sodium hydroxide. Activation of APC by these glucans were dependent on incubation time, concentration, molecular weight, and DB. Interestingly, the triple helix conformer of all glucans tested activated APC stronger than a single helix one. The activity of branched glucans in plasma was weaker than those in serum. On the other hand, in the case of CPC, a single helix conformer activated CPC stronger than a triple helix one, and the activity was dependent on DB. Activation of CPC by a single helix conformer was thought to be dependent on the binding of beta-glucan to immunoglobulin in serum, because the complex was clearly detected by gel permeation chromatography only in the case of single helix one. From these results, it appears that the different conformers were recognized by the host complement systems in different ways. (1----3)-beta-D-Glucan is one of the major constituents of fungal cell wall and is thought to be clearly recognized by the host immune systems.(ABSTRACT TRUNCATED AT 250 WORDS)","PeriodicalId":16743,"journal":{"name":"Journal of pharmacobio-dynamics","volume":"15 6","pages":"277-85"},"PeriodicalIF":0.0,"publicationDate":"1992-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1248/bpb1978.15.277","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12604515","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}

引用次数: 42

Proceedings of the 13th Symposium on the Interaction between Biological Membranes and Drugs. Tokyo, November 15-16, 1991. 第十三届生物膜与药物相互作用学术研讨会论文集。1991年11月15日至16日，东京。

Journal of pharmacobio-dynamics Pub Date : 1992-06-01

引用次数: 0

Brain and cerebrospinal fluid distributions of metoprolol in rats. 美托洛尔在大鼠脑和脑脊液中的分布。

Journal of pharmacobio-dynamics Pub Date : 1992-06-01 DOI: 10.1248/bpb1978.15.295

T Nakazono, T Murakami, S Sakai, Y Higashi, N Yata

{"title":"Brain and cerebrospinal fluid distributions of metoprolol in rats.","authors":"T Nakazono, T Murakami, S Sakai, Y Higashi, N Yata","doi":"10.1248/bpb1978.15.295","DOIUrl":"https://doi.org/10.1248/bpb1978.15.295","url":null,"abstract":"The distribution of metoprolol tartrate (MPL) into the brain and cerebrospinal fluid (CSF) from plasma was determined at 2 different steady-state plasma concentrations (2 and 20 nmol/ml) and following intravenous bolus administration (100 nmol/kg) in rats. Under steady-state condition, no difference in the brain and CSF distributions of MPL was observed between 2 different plasma MPL concentrations, and the value of brain- or CSF-to-plasma partition coefficients were 5.7 and 1.5, respectively. Following intravenous administration, MPL distributed into CSF very rapidly and its initial uptake phase was not detected. On the other hand, MPL distribution into the brain was relatively slow with the uptake phase. Thus, the brain uptake of MPL from the plasma was pharmacokinetically analyzed using a modified 2-compartment model and deconvolution method, whereas the CSF distribution of MPL was not adequate for kinetic analysis because of the lack of uptake phase. The analysis of brain uptake of MPL by both compartment model and deconvolution gave the same results and the calculated brain Kp value of MPL was almost comparable with that of observed Kp value under steady-state plasma concentration. The distribution of MPL into CSF was considered mainly depending on the pH difference between the plasma and CSF, and the mutual transfer of MPL between CSF and the brain tissue was considered to be negligible from an in vitro study.","PeriodicalId":16743,"journal":{"name":"Journal of pharmacobio-dynamics","volume":"15 6","pages":"295-302"},"PeriodicalIF":0.0,"publicationDate":"1992-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1248/bpb1978.15.295","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12604517","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}

引用次数: 2

Studies on responsiveness of hepatoma cells to catecholamines. VI. Characteristics of adrenoceptors and adenylate cyclase response in rat ascites hepatoma cells and human hepatoma cells. 肝癌细胞对儿茶酚胺反应性的研究。六、大鼠腹水肝癌细胞和人肝癌细胞中肾上腺素受体和腺苷酸环化酶反应的特点。

Journal of pharmacobio-dynamics Pub Date : 1992-06-01 DOI: 10.1248/bpb1978.15.303

F Sanae, K Kohei, M Nomura, K Miyamoto

{"title":"Studies on responsiveness of hepatoma cells to catecholamines. VI. Characteristics of adrenoceptors and adenylate cyclase response in rat ascites hepatoma cells and human hepatoma cells.","authors":"F Sanae, K Kohei, M Nomura, K Miyamoto","doi":"10.1248/bpb1978.15.303","DOIUrl":"https://doi.org/10.1248/bpb1978.15.303","url":null,"abstract":"Alpha 1, alpha 2- and beta-Adrenoceptor densities and catecholamine responsiveness in established hepatoma cells, rat ascites hepatoma AH13, AH66, AH66F, AH109A, AH130 and AH7974 cells and human hepatocellular carcinoma HLF and HepG2 cells, were compared with those in normal rat hepatocytes and Chang liver cells. Alpha 1-Adrenoceptor densities measured by [3H]prazosin bindings were not detected in all hepatoma cell lines. Alpha 2-Adrenoceptor densities measured by [3H]clonidine bindings were also barely detected in hepatoma cell lines except for AH130 cells and HepG2 cells. Regarding beta-adrenoceptor, AH109A, AH130 and AH7974 cells had much more [125I]iodocyanopindolol binding sites than normal rat hepatocytes, although we could not detect the binding in HepG2 cells. Adenylate cyclase of normal rat hepatocyte and Chang liver cells were stimulated by beta 2-adrenergic agonist salbutamol, while the cyclase in hepatoma cells had no beta 2-adrenergic response but a beta 1-type response. These findings indicate that the characteristics of adrenergic response in hepatoma cell lines is very different from that in normal hepatocytes, suggesting a participation in the hepatocarcinogenesis and/or the autonomous proliferation of hepatoma cells.","PeriodicalId":16743,"journal":{"name":"Journal of pharmacobio-dynamics","volume":"15 6","pages":"303-9"},"PeriodicalIF":0.0,"publicationDate":"1992-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1248/bpb1978.15.303","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12504179","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}

引用次数: 5

Mechanism of hepatic microsomal oxidation of 11-hydroxy-delta 8-tetrahydrocannabinol to 11-oxo-delta 8-tetrahydrocannabinol. Evidence for hydration of the aldehyde formed. 肝微粒体氧化11-羟基- δ 8-四氢大麻酚为11-氧- δ 8-四氢大麻酚的机制。形成了醛水合作用的证据。

Journal of pharmacobio-dynamics Pub Date : 1992-06-01 DOI: 10.1248/bpb1978.15.311

K Watanabe, T Matsunaga, S Narimatsu, I Yamamoto, H Yoshimura

{"title":"Mechanism of hepatic microsomal oxidation of 11-hydroxy-delta 8-tetrahydrocannabinol to 11-oxo-delta 8-tetrahydrocannabinol. Evidence for hydration of the aldehyde formed.","authors":"K Watanabe, T Matsunaga, S Narimatsu, I Yamamoto, H Yoshimura","doi":"10.1248/bpb1978.15.311","DOIUrl":"https://doi.org/10.1248/bpb1978.15.311","url":null,"abstract":"Hepatic microsomal oxidation of 11-hydroxy-delta 8-tetrahydrocannabinol (11-OH-delta 8-THC) to 11-oxo-delta 8-THC was investigated. Hepatic microsomes from mice, rats, guinea pigs and rabbits catalyzed the oxidation of 11-OH-delta 8-THC to 11-oxo-delta 8-THC together with the formation of dihydroxy-delta 8-THCs oxidized at the 7-position or at the pentyl side chain of 11-OH-delta 8-THC. 11-Oxo-delta 8-THC formed under oxygen-18 gas was analyzed by gas chromatography-mass spectrometry (GC-MS) indicating that molecular oxygen was not significantly incorporated into the aldehyde formed. 11-Oxo-delta 8-THC formed from 11-18OH-delta 8-THC (18O/16O = 0.81 - 1.05) was also found to lose oxygen-18 from the molecule. These results suggest that 11-oxo-delta 8-THC is hydrated in the incubation mixture and the aldehyde oxygen is exchangeable with the oxygen atom of water. When 11-oxo-delta 8-THC was incubated with hepatic microsomes and phosphate buffer containing H2 18O (44 atom%), GC-MS analysis indicated the incorporation of oxygen-18 into the aldehyde recovered from the incubation mixture. The results suggest that the hepatic microsomes may facilitate the hydration of 11-oxo-delta 8-THC and exchange an oxygen atom of the aldehyde group with that of water in the incubation mixture.","PeriodicalId":16743,"journal":{"name":"Journal of pharmacobio-dynamics","volume":"15 6","pages":"311-7"},"PeriodicalIF":0.0,"publicationDate":"1992-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1248/bpb1978.15.311","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12504180","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}

引用次数: 2

Clinical management of boric acid ingestion: pharmacokinetic assessment of efficacy of hemodialysis for treatment of acute boric acid poisoning. 摄入硼酸的临床处理:血液透析治疗急性硼酸中毒疗效的药代动力学评价。

Journal of pharmacobio-dynamics Pub Date : 1992-06-01 DOI: 10.1248/bpb1978.15.287

D Teshima, K Morishita, Y Ueda, K Futagami, S Higuchi, T Komoda, F Nanishi, T Taniyama, J Yoshitake, T Aoyama

{"title":"Clinical management of boric acid ingestion: pharmacokinetic assessment of efficacy of hemodialysis for treatment of acute boric acid poisoning.","authors":"D Teshima, K Morishita, Y Ueda, K Futagami, S Higuchi, T Komoda, F Nanishi, T Taniyama, J Yoshitake, T Aoyama","doi":"10.1248/bpb1978.15.287","DOIUrl":"https://doi.org/10.1248/bpb1978.15.287","url":null,"abstract":"Seven hours after suicidal ingestion of about 21 g of boric acid, a 26-year-old female admitted to our hospital in a state of slightly impaired consciousness, with frequent vomiting, shivering, fever and skin flush. Immediately, gastric lavage, followed by administration of activated charcoal and laxative (MgSO4), was performed. In order to ensure her urination, fluid infusion therapy was conducted with the aid of diuretics (furosemide). Since the serum concentrations of boric acid was very high, hemodialysis was carried out twice during the first 39 h. She responded well to the above mentioned treatment and was discharged 12 d post-admission without any sequelae. The concentrations of boric acid in serum and urine were measured in appropriate intervals with our modified Miyamoto's method, and the pharmacokinetics of boric acid were analyzed. The concentration of boric acid in serum and urine at the beginning of treatment was 465 micrograms/ml and 3.40 mg/ml, respectively. The half-life of boric acid in serum was 13.46 h, whereas it was shortened to 3.76 h during hemodialysis. The total body clearance was 0.99 l/h, while it increased to 3.53 l/h by hemodialysis. The additional removal of boric acid by hemodialysis was estimated to be about 5 g. It was concluded that the hemodialysis was very useful in the treatment of boric acid poisoning, because it accelerated the elimination of boric acid about four times faster than with conventional treatment.","PeriodicalId":16743,"journal":{"name":"Journal of pharmacobio-dynamics","volume":"15 6","pages":"287-94"},"PeriodicalIF":0.0,"publicationDate":"1992-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1248/bpb1978.15.287","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12604516","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}

引用次数: 21

Inducible resistance to a 16-membered macrolide, mycinamicin, in Staphylococcus aureus resistant to 14-membered macrolides and streptogramin B antibiotics. 金黄色葡萄球菌对14元大环内酯类和链状gramin B抗生素耐药，对16元大环内酯类，mycinamicin的诱导抗性。

Journal of pharmacobio-dynamics Pub Date : 1992-06-01 DOI: 10.1248/bpb1978.15.319

Y Nakajima, L Jánosi, K Endou, M Matsuoka, H Hashimoto

{"title":"Inducible resistance to a 16-membered macrolide, mycinamicin, in Staphylococcus aureus resistant to 14-membered macrolides and streptogramin B antibiotics.","authors":"Y Nakajima, L Jánosi, K Endou, M Matsuoka, H Hashimoto","doi":"10.1248/bpb1978.15.319","DOIUrl":"https://doi.org/10.1248/bpb1978.15.319","url":null,"abstract":"Staphylococcus aureus 8325(pEP2104), a transductant derived from S. aureus PM2104 isolated clinically in Hungary (L. Janosi, and E. Ban, Acta Microbiol. Acad. Sci. Hung., 29: 187-200, 1982), exhibited an inducible resistance to the 14-membered macrolides [erythromycin (EM) and oleandomycin (OL)] and streptogramin B (MKM-B) antibiotics, but not to the 16-membered macrolides and lincosamides. This resistance was referred to as PMS-resistance phenotype (L. Jánosi, Y. Nakajima, and H. Hashimoto, Microbiol. Immunol., 34: 723-735, 1990). In addition to EM, OL, and MKM-B, however, the strain was recently and first observed to have inducible resistance to mycinamicin, a 16-membered ring macrolide. Thereby, we propose that the reference stated just above as PMS-resistance has to be extended to such 16-membered macrolides as mycinamicin. An optimum concentration of erythromycin or oleandomycin for induction of PMS-resistance was 1.35 mu g/ml in the strain 8325(pEP2104). The concentration was about 30 times as great as that (0.05 mu g/ml) required for induction of well-known co-resistance to macrolide-lincosamide-streptogramin B antibiotics in S. aureus ISP447.","PeriodicalId":16743,"journal":{"name":"Journal of pharmacobio-dynamics","volume":"15 6","pages":"319-24"},"PeriodicalIF":0.0,"publicationDate":"1992-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1248/bpb1978.15.319","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12604518","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}

引用次数: 6

Trans-prostaglandin E2 enhances fibrinolysis. 反式前列腺素E2增强纤溶。

Journal of pharmacobio-dynamics Pub Date : 1992-05-01 DOI: 10.1248/bpb1978.15.261

T Urano, M Shimokawa, T Kinoshita

引用次数: 2