摘要:

The relative distribution of verapamil and its demethylated metabolite, norverapamil, was studied in rats at intervals after intraperitoneal injection of the parent drug (30 mg/kg). This route of drug administration simulated oral drug dosing, and the highest concentrations of both unchanged drug and metabolite were found in the liver, with lung and kidney containing most of the remainder. The rates of disappearance of verapamil from various organs followed first-order kinetics, and the most rapid elimination occurred from brain and liver. In contrast, verapamil was given intravenously to 3 dogs by a bolus-infusion method to produce sustained steady state plasma concentrations (80, 140, 250 ng/ml) for 1, 2, and 3 h. After systemic administration, the lungs contained almost half the tissue verapamil and, 20% was found in kidney, with the liver accounting for only 17%. Norverapamil was not found in plasma or brain. These studies contrast the pattern of tissue distribution of verapamil after different routes of drug administration. The variable rates of drug elimination from specific tissues may explain the differing durations of the drug’s observed effect

ISSN:0031-7012    

DOI:10.1159/000137823

出版商:S. Karger AG    

年代:1983

数据来源: Karger

摘要:

In isolated and enriched guinea pig parietal cells the inhibitory effects of the calcium channel antagonists verapamil and gallopamil on 14C-aminopyrine uptake (= H+ secretion) have been analyzed. Both verapamil and gallopamil inhibit acid secretion in a concentration-dependent manner with an IC50 of 12.1 and 10.9 μmol/l respectively. The type of inhibition is noncompetitive in nature. Verapamil inhibits the acid respone to histamine, dibutyryl-cAMP, and KC1 with IC50 values not significantly different from each other. Exposure of the cells to verapamil and subsequent washing enhances the acid response to histamine for an unknown reason. It is concluded that the calcium channel antagonists verapamil and gallopamil inhibit acid secretion in vitro by interfering with the parietal cell proton pump, the K+/H+-ATPase

ISSN:0031-7012    

DOI:10.1159/000137824

出版商:S. Karger AG    

年代:1983

数据来源: Karger

摘要:

The effects of aspirin and suprofen on gastrointestinal blood loss were compared in a double-blind, crossover study of 20 healthy male subjects. Fecal blood loss was measured by 51Cr-labeled red cells. Subjects treated with aspirin (2,600 mg/day) experienced a mean fecal blood loss of 4.2 ml/day, compared with subjects treated with suprofen (800 mg/day) whose mean fecal blood loss was 1.8 ml/day. There was significantly greater (p < 0.01) blood loss in the aspirin group than in the suprofen group. Mean fecal blood loss in the suprofen group did not differ appreciably from the fecal blood loss observed during the placebo period (0.4 ml/day).

ISSN:0031-7012    

DOI:10.1159/000137895

出版商:S. Karger AG    

年代:1983

数据来源: Karger

摘要:

Hormonal and cholinergic influences on lysosomal and digestive enzyme activities in pancreatic tissue were studied in normal adult rats. Hormonal stimulation by the cholecystokinin analogue, caerulein, induced a marked enhancement of the activities of cathepsin D and N-acetyl-β-D-glucosaminidase in pancreatic tissue, whereas the activities of amylase and lipase tended to decrease. Acid phosphatase activity was not affected. Further, caerulein was found to induce a significant increase of cathepsin D output in bile-pancreatic juice. This output largely parallelled that of amylase. Cholinergic stimulation by the muscarinic agonist carbachol, at a dose level giving the same output of amylase as caerulein, did not affect pancreatic activities of cathepsin D and N-acetyl-β-D-glucosaminidase. Further, cholinergic stimulation induced an increase of amylase activity and a slight decrease of acid phosphatase activity in pancreatic tissue. Lipase activity was not affected. No apparent effect on cathepsin D output in bile-pancreatic juice was encountered after cholinergic stimulation. The activities of neither the digestive nor the lysosomal enzymes were influenced by the administration of secretin. The results suggest a possible lysosomal involvement in caerulein-induced secretion and/or inactivation of pancreatic digestive enzymes, whereas cholinergic stimulation seems to act through different mechanism

ISSN:0031-7012    

DOI:10.1159/000137825

出版商:S. Karger AG    

年代:1983

数据来源: Karger

摘要:

Effects on blood pressure and heart rate of prostaglandin (PG) F2α administered into a lateral cerebral ventricle (i.e.v.) were investigated in urethane anesthetized rats. PG F2α at doses ranging from 2.4 to 47.4 μg caused dose-dependent pressor and positive chronotropic actions, but did not exert such actions at a dose of 47.4 μg in spinal rats. The cardiovascular actions of PG F2α were reduced by intravenous (i.v.) pretreatment with hexamethonium (2 mg/kg). In addition, the pressor action was blocked by phentolamine (5 mg/kg i.v.) and the positive chronotropic action by propranolol (0.2 mg/kg i.v.). PG F2α (47.4 μg) and norepinephrine (2 μg/kg) injected i.v. induced transient pressor and positive chronotropic actions. This pressor action of norepinephrine was almost completely eliminated but that of PG F2α was only partially inhibited by phentolamine (5 mg/kg i.v.), while the positive chronotropic actions were unaffected. The results suggest that PG F2α accelerates the cardiovascular functions by stimulating the peripheral sympathetic tone through its centr

ISSN:0031-7012    

DOI:10.1159/000137826

出版商:S. Karger AG    

年代:1983

数据来源: Karger

摘要:

21 unilateral breast cancer patients taking different combinations of chemotherapeutic agents (cyclophosphamide, methotrexate, 5-fluorouracil, vincristine, and prednisone) were studied to determine how chemotherapy affected their granulocytes. It is widely believed that in cancer patients chemotherapeutic agents increase susceptibility to infection. Therefore, luminol-enhanced chemiluminescence was used to evaluate leukocyte function since the chemiluminescence response has been correlated to bacterial killing. The chemiluminescence response in cancer patients (6-week treatment) was significantly reduced (approximately 50%; p < 0.01) compared to nontreated volunteers. Preliminary studies using 3H-formyl-methionyl-leucyl-phenyl alanine binding showed similar decreases. We postulate that chemotherapy for 6 weeks may affect granulocyte precursor cells in bone marrow, thereby weakening peripheral granulocytes and reducing both their bactericidal capacity and 3H-formyl-methionyl-leucyl-phenyl alanine receptors.

ISSN:0031-7012    

DOI:10.1159/000137827

出版商:S. Karger AG    

年代:1983

数据来源: Karger

摘要:

The purpose of this study was to evaluate the analgesic efficacy and safety of single oral doses of suprofen 200 and 400 mg, compared with aspirin 650 plus codeine 60 mg, aspirin 650 mg, and placebo in the relief of moderate to severe pain resulting from the surgical removal of impacted third molars. 157 patients completed a randomized, double-blind, single-dose, stratified, parallel-groups trial, and were observed for at least 4 h. Based upon each of the summary efficacy measures, sum pain intensity difference (SPID), percent SPID, TOTPAR and a global evaluation, all four active treatments were approximately equally effective and all were statistically superior to placebo. In addition, suprofen at both dose levels was significantly more effective than placebo beginning at the 0.5-hour observation for mean pain intensity, whereas the two aspirin treatments were not superior to placebo until the 1-hour observation. Side effects were minimal; there was one in the suprofen 200 mg, three in the aspirin 650 mg, and one in the placebo treatment group. Thus, it appears that suprofen at 200 and 400 mg is a safe and effective oral analgesic for the relief of moderate or severe postoperative dental pain, and it is possible that compared to aspirin 650 mg and aspirin 650 mg plus codeine 60 mg, it has a more rapid onset of action.

ISSN:0031-7012    

DOI:10.1159/000137897

出版商:S. Karger AG    

年代:1983

数据来源: Karger

摘要:

The anticonvulsant activity (ED50) of three synthetic eugenol derivatives – phenyleugenol (PE), benzyleugenol (BE), phenylethyleugenol (PEE) – was compared to that of common antiepileptics – diphenyl-hydantoine (DPH), phenobarbital (PB), diazepam (DZ) -and the naturally occurring methyleugenol (ME) in the maximal electroshock seizure (MES) test and the subcutaneous pentylenetetrazol-induced minimal seizure (s.c. PTZ) test. Neurotoxicity (ND50) and lethality (LD50) were determined in order to evaluate the protective index (PI = ND50/ED50) and the therapeutic index (TI = LD50/ED50). BE, PE and PEE are shown to be effective anticonvulsants by the MES test in mice with PIs equal to or higher than that of PB and DZ. Furthermore, BE and PEE were significantly more potent in rats than in mice. Experiments on the duration of protection revealed an immediate onset, a steady decline within the following 4 h and reappearance of activity 6–8 h after injection of PE, BE, and PEE but not ME. In the s.c. PTZ test in mice, the eugenol derivatives were active in increasing the latency to the first minimal seizure but less active in its prevention. As to the TIs, PEE showed a smaller margin of safety by the two tests than BE and PE. The latter compounds have high LD50s and consequently h

ISSN:0031-7012    

DOI:10.1159/000137828

出版商:S. Karger AG    

年代:1983

数据来源: Karger

摘要:

43 patients with osteoarthritis of the knee and/or hip(s) were treated with suprofen 800 mg/day or ibuprofen 1,600 mg/day for 14 days. Both drugs produced an improvement in subjective symptoms by day 7, although the most rapid analgesic effect was obtained with suprofen. Patients receiving suprofen experienced a significantly greater improvement in pain on motion at day 7 than did patients taking ibuprofen. Patients and investigators evaluated both drugs as having good to very good efficacy in the great majority (over 75%) of cases. Both drugs were well tolerated, with only a single drug withdrawal in the ibuprofen group.

ISSN:0031-7012    

DOI:10.1159/000137898

出版商:S. Karger AG    

年代:1983

数据来源: Karger

摘要:

The safety and efficacy of suprofen 200 mg q.i.d. and aspirin 650 mg q.i.d. in the treatment of chronic pain due to osteoarthritis were compared in a double-blind, randomized, parallel group study over a 12-week period. Suprofen was comparable to aspirin in the relief of pain and improvement in activity impairment. Results of ocular examination, laboratory data, and vital signs examinations indicated no clinically significant changes for suprofen. No serious side effects were reported by either group.

ISSN:0031-7012    

DOI:10.1159/000137899

出版商:S. Karger AG    

年代:1983

数据来源: Karger