ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1984.tb01822.x

出版商:Blackwell Publishing Ltd    

年代:1984

数据来源: WILEY

摘要:

Abstract:The possibility that lipid peroxidation is involved in valproic acid (VPA) hepatotoxicity was explored by testing the ability of the free‐radical scavengers α‐tocopherol (vitamin E) and N,N'‐diphenyl‐p‐phenylenediamine (DPPD) to protect against VPA toxicity. Rat hepatocyte cultures were treated with toxic doses of VPA, in conjunction with varying doses of vitamin E and DPPD. Lactate dehydrogenase (LDH) release into the culture media was used to calculate an LDH index as a measure of toxicity. Vitamin E afforded increasing protection against VPA toxicity at concentrations of 1.0 to 4.0 μM but then leveled off and did not give complete protection at concentrations up to 8.0 μM. No protection was seen at less than 1.0 μM. DPPD showed increasing protection from 0.05 to 0.50 μM, with complete protection at the highest concentration. These data indicate that VPA toxicity can be prevented by simultaneous administration of free‐radical scavengers and support the concept that VPA hepatotoxicity is due to li

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1984.tb01823.x

出版商:Blackwell Publishing Ltd    

年代:1984

数据来源: WILEY

摘要:

Abstract:Twenty cancer patients who received chemotherapy were entered into a double‐blind crossover design antiemetic study comparing 1 mg levonantradol, an investigational synthetic cannabinoid, to 10 mg prochlorperazine. Sixteen patients completed the crossover. For each antiemetic course, four doses of each study medication were given intramuscularly 2 hours before chemotherapy and then 2,6, and 10 hours after chemotherapy administration. There were no statistical differences in patients' responses to levonantradol and prochlorperazine. The frequency of side effects was greater with levonantradol than with prochlorperazine. The most common side effect of levonantradol were somnolence, dry mouth, dizziness, tachycardia, postural hypotension, and blurred vision, while those for prochlorperazine were somnolence, dry mouth, and tachycardi

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1984.tb01824.x

出版商:Blackwell Publishing Ltd    

年代:1984

数据来源: WILEY

摘要:

Abstract:To determine if ordinary doses of nitrates produce a significant increase in methemoglobin, methemoglobin levels were measured in 59 randomly selected patients with coronary artery disease and unstable angina pectoris who were receiving organic nitrate therapy. Patients were taking isosorbide dinitrate, 2% nitroglycerin ointment, or a combination of the two. Patients were subdivided according to whether they were using one (group A) or more than one (group B) organic nitrate preparations. These results were compared with 17 control patients. Mean methemoglobin levels in group B were 1.78 ± 1.29%, and this differed significantly (P<0.05) from both group A mean methemoglobin, 1.13 ± 0.92%, and controls, 0.99 ± 0.55%. The proportion of patients with elevated methemoglobin concentration increased from the control to group A to group B. It is concluded that commonly used dosages of nitrates are capable of causing elevations of methemoglobin which are probably not of routine clinical significance. However, these elevations may be of import in certain patient populations such as those with coronary insufficiency or anem

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1984.tb01825.x

出版商:Blackwell Publishing Ltd    

年代:1984

数据来源: WILEY

摘要:

Abstract:The pharmacokinetic behavior and hemodynamic effects of tiapamil, a calcium antagonist, were studied in 16 cardiac patients during an eight‐day treatment course, giving oral doses of 600 mg daily. The hemodynamic effects were investigated using exercise performance tests, thallium stress scintigraphy, and radionuclide ventriculography. The areas under the plasma concentration‐time curve after the final dose were greater than after the first dose for both tiapamil (+53 per cent) and its metabolite (+24 per cent). One possible explanation is that tiapamil undergoes saturable intestinal wall metabolism. Alternatively, like verapamil, it may undergo a saturable hepatic elimination process. The hemodynamic test series showed that, despite increasing the exercise tolerance, tiapamil significantly reduced the rate‐pressure product, an index of myocardial oxygen requirement. Regional myocardial perfusion clearly improved. Ventriculography showed a significant increase in ejection fraction (+18 per cent), cardiac index (+12 per cent), and stroke volume index (+19 per cent). At the same time, the measured mean arterial pressure decreased significantly by about 10 per cent and the calculated peripheral vascular resistance, by about 19 per

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1984.tb01826.x

出版商:Blackwell Publishing Ltd    

年代:1984

数据来源: WILEY

摘要:

Abstract:The pharmacokinetic interaction of the monobactam antibiotic aztreonam with cephradine, clindamycin, gentamicin, metronidazole, and nafcillin was investigated in five separate studies in 48 healthy male volunteers. All drugs were administered by 30‐minute intravenous infusions in single‐dose, three‐way balanced crossover studies. Drug levels were measured in serum, protein‐free filtrate of serum, and urine. Small changes of no clinical significance were seen when aztreonam was given simultaneously with another antibiotic as compared with each drug alone. Maximum serum concentrations of aztreonam were reduced by 12.6 and 9.8 per cent when it was given with gentamicin and metronidazole, respectively. The percentage of serum aztreonam bound to protein fell by a maximum of 5.0 per cent when the monobactam was given in conjunction with nafcillin and rose by 5.1 per cent when accompanied by cephradine. Twenty‐four‐hour cumulative urinary excretion of aztreonam and clindamycin rose by 5.2 and 10.9 per cent, respectively, when they were administered sim

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1984.tb01827.x

出版商:Blackwell Publishing Ltd    

年代:1984

数据来源: WILEY

摘要:

Abstract:The comparative bioavailability of chloramphenicol from intravenous succinate, oral palmitate, and oral base preparations was studied in a crossover manner in 12 adult patients. Chloramphenicol was administered at a dose of 1 Gm every 6 hours, and blood samples were collected at steady state. For the succinate study, total urine output was also collected. The bioavailability of active chloramphenicol from the succinate preparation averaged 85.8 ± 42.3 and 78.8 ± 50.1 per cent of the free base and palmitate forms, respectively. This lower availability appeared to be due to variable excretion of unchanged succinate in the urine, averaging 27 ± 11 per cent of the dose. Regardless of dosage form or route of administration, plasma chloramphenicol concentrations remained in the therapeutic range (5 to 25 mg/liter) for the entire dosage interval, implying that no change needs to be made when changing dosage form or route of administration. The interpatient variability, however, supports the need for monitoring of plasma chloramphenicol concentrations, especially in newborn infants, persons with liver disease, or those receiving other medications that alter chloramphenicol metaboli

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1984.tb01828.x

出版商:Blackwell Publishing Ltd    

年代:1984

数据来源: WILEY

摘要:

Abstract:The influence of Cimetidine coadministration, 300 mg every 6 hours, on the kinetics of single oral doses of oxazepam (30 mg), lorazepam (2 mg), and flurazepam (30 mg) was evaluated in healthy volunteers. Cimetidine had no significant effect on the peak plasma concentration or the time of peak concentration for either oxazepam, lorazepam, or desalkylflurazepam (formed from flurazepam). Cimetidine likewise did not alter the elimination half‐life of oxazepam (9.4 hours) or lorazepam (11.6 hours), and did not change total AUC for lorazepam. Oxazepam AUC was increased an average of 10 per cent by Cimetidine (P<0.02). In contrast, Cimetidine prolonged desalkylflurazepam elimination half‐life (141 vs. 94 hours,P<0.1) and increased AUC an average of 65 per cent (P<0.05). Thus, Cimetidine has little or no influence on the absorption or disposition of oxazepam and lorazepam, two benzodiazepines biotransformed by glucuronide conjugation. However, Cimetidine slows the elimination of flurazepam's metabolite, desalkylflurazepam, which is biotransformed by oxidat

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1984.tb01829.x

出版商:Blackwell Publishing Ltd    

年代:1984

数据来源: WILEY

摘要:

Abstract:The influence of food on the bioavailability of trimoprostil, a new antiulcer prostaglandin E2derivative, was investigated in healthy male volunteers in four separate studies. Doses of 0.75, 1.5, and 3.0 mg were administered orally in both the presence and absence of food followed by serial blood sampling through 24 hours. Plasma trimoprostil concentrations were determined by a gas chromatographnegative chemical ionization‐mass spectrometric method for pharmacokinetic evaluation. Food decreased the absorption rate of trimoprostil as indicated by a later tmax(P0.05) across all doses and ranged from 27 to 55 minu

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1984.tb01830.x

出版商:Blackwell Publishing Ltd    

年代:1984

数据来源: WILEY

摘要:

Twoneuroleptics, haloperidol and chlorpromazine, have been reported to be effective in the treatment of phencyclidine (PCP) psychosis. Both neuroleptics are thought to exert their antipsychotic PCP effects by blockade of central dopamine receptors. They have been studied extensively in animal populations and less extensively in human populations. There has, however, been no comparison of their relative effects in human populations. We describe such a study below.

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1984.tb01831.x

出版商:Blackwell Publishing Ltd    

年代:1984

数据来源: WILEY