ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1983.tb01795.x

出版商:Blackwell Publishing Ltd    

年代:1983

数据来源: WILEY

摘要:

Abstract:In this long‐term, double‐blind, multicenter study, efficacy and safety of zomepirac sodium were compared with those of aspirin for treatment of the chronic pain associated with osteoarthritis in 607 patients, 405 of whom received zomepirac and 202 of whom received aspirin. Final evaluations during one year of treatment showed zomepirac significantly more effective than aspirin for reducing pain at rest (P= 0.02) and average pain (P= 0.04). Moreover, zomepirac was rated better than aspirin in physician global evaluations of overall response to therapy (P= 0.02) and patient evaluations of pain relief (P= 0.03). At the end of the one‐year study, patients were permitted to extend double‐blind treatment for an additional year. In final evaluations for patients who continued, zomepirac was significantly better than aspirin for relief of pain on motion (P= 0.05) and also in patient global evaluations of therapeutic response (P= 0.02). Side effect profiles during the first year of therapy were generally comparable for zomepirac and aspirin. However, complaints related to the special senses, especially tinnitus and hearing disturbances, were reported more frequently during aspirin therapy, and urogenital side effects were more common during zomepirac therapy. For both drug groups, the overall incidence of side effects was lower in the second year than in the first. This is the first published study to show a nonsteroidal anti‐inflammatory agent to be more effective than aspirin for the long‐term treatment of pain associated with ost

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1983.tb01796.x

出版商:Blackwell Publishing Ltd    

年代:1983

数据来源: WILEY

摘要:

Abstract:Flutroline hydrochloride, a gamma carboline manifesting neuroleptic activity, was administered in a double‐blind fashion in single daily dosages of 1, 5, 10, 20, and 100 mg to 48 hospitalized schizophrenic patients over a period of four weeks. During this period, weekly evaluations were made of response employing standardized psychiatric ratings. Plasma prolactin (PRL) levels were obtained at the termination of previous neuroleptic medication and at two‐week intervals during treatment with the investigational compound. Examination of the initial PRL levels indicated that they could be grouped into those above, within, and below the normal range. Comparisons of these initial levels with those following the administration of flutroline suggested an improved methodology for determining optimal neuroleptic dos

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1983.tb01797.x

出版商:Blackwell Publishing Ltd    

年代:1983

数据来源: WILEY

摘要:

Abstract:The influence of therapeutic doses of ibuprofen on the distribution and clearance of antipyrine in humans was evaluated in a series of healthy volunteers. Subjects received a single intravenous dose of antipyrine on two occasions, once in the drug‐free control state and again during coadministration of ibuprofen, 1.6 to 2.4 Gm per day in divided doses. Compliance was verified by measurement of plasma ibuprofen levels, which averaged 22 μg/ml. Kinetic variables for antipyrine were determined from multiple plasma antipyrine concentrations measured during 24 hours after each dose. Between drug‐free control and ibuprofen coadministration trials, there was no significant difference in antipyrine volume of distribution (0.69 vs. 0.69 liter/kg), elimination half‐life (12.2 vs. 12.5 hours), or total metabolic clearance (0.69 vs. 0.70 ml/min/kg). Thus, ibuprofen does not impair the clearance of the marker compound antipyrine, often used as an index of drug oxidizing capacity in

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1983.tb01798.x

出版商:Blackwell Publishing Ltd    

年代:1983

数据来源: WILEY

摘要:

Abstract:The pharmacokinetics and metabolism of stiripentol, a new antiepileptic drug, were investigated in normal male subjects after single‐dose and multiple‐dose administration. Each of six subjects received single doses of 300,600, and 1200 mg of stiripentol in powder form and another 600 mg in solution. In the multiple‐dose study, each of six subjects received a 300‐mg dose on day 1 and multiple doses (1200 mg/day) from day 2 to day 8. Five of these six subjects participated also in the single‐dose study. Stiripentol and several of its metabolites, namely, stiripentol conjugate, DiOH, P‐OH, and M‐OH, were analyzed in plasma and urine. After single doses, the elimination curve of stiripentol appeared multiphasic. The oral clearance was 1.3 to 1.8 liter/hr/kg. The average mean residence time was 4 hours. There were no statistically significant differences in clearance or mean residence time among the three doses. However, dose dependence was found in all the four pathways when formation clearances were compared. Only trace amounts of the drug were excreted unchanged in urine. The active metabolite, P‐OH, was not detectable in plasma. Stiripentol was very highly bound to plasma proteins in plasma from dosed subjects as well as spiked human plasma (free fraction of 1 per cent). In the multiple‐dose study, there was a decrease (nearly eightfold) in oral clearance of stiripentol between day 1 and day 8. The fractions of dose metabolized through conjugation and methylenedioxy ring opening increased 183 and 49 per cent, respectively, but the formation clearances for all the pathways were decreased. These findings suggest that the steady‐state plasma level/dose ratio of stiripentol will increase

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1983.tb01799.x

出版商:Blackwell Publishing Ltd    

年代:1983

数据来源: WILEY

摘要:

Abstract:Twenty healthy male subjects received 80 mg (2 × 40 mg SEG capsules) oral isotretinoin separated by two‐week washout periods in an open randomized crossover design. Isotretinoin was administered during a complete fast, 1 hour after a standard breakfast, with a standard breakfast, or 1 hour before a standard breakfast. Blood samples were obtained at specific times over a 72‐hour period. Isotretinoin blood concentrations were determined by a specific HPLC method. The relative bioavailability (AUC) of isotretinoin was found to be approximately 1.5 to 2 times greater when the dose was administered 1 hour before, concomitantly with, or 1 hour after a meal than when it was given during a complete fast. In addition, because the Cmax, value is lower when the dose is administered with food rather than 1 hour after a meal, coadministration of isotretinoin with food may be the best method of administra

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1983.tb01800.x

出版商:Blackwell Publishing Ltd    

年代:1983

数据来源: WILEY

摘要:

Abstract:The effect of both concomitant administration and pretreatment with isoniazid on the activity of the hepatic drug‐metabolizing enzymes of healthy young volunteers, as indicated by the antipyrine clearance test, is reported. Concomitant administration of isoniazid with antipyrine results in a significant decrease in the hepatic clearance of the latter compound. In contrast, pretreatment for 14 days with isoniazid had no effect on antipyrine elimination kinetics. It is concluded that isoniazid depresses hepatic drug metabolism only when present in significant amounts at the hepatic site of drug oxidatio

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1983.tb01801.x

出版商:Blackwell Publishing Ltd    

年代:1983

数据来源: WILEY

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1983.tb01802.x

出版商:Blackwell Publishing Ltd    

年代:1983

数据来源: WILEY

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1983.tb01803.x

出版商:Blackwell Publishing Ltd    

年代:1983

数据来源: WILEY

摘要:

Abstract:Captopril was tested as the treatment for a patient with primary pulmonary hypertension (PPH) and its effects were compared with those of hydralazine. Captopril induced a rise in pulmonary pressures and in intrapulmonary shunt; hydralazine lowered pulmonary resistances and increased paO2and blood O2transport. Prospective studies in PPH treated with captopril are recommended and evaluation of all drugs not only by hemodynamic but also respiratory and O2transport measurements.

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1983.tb01804.x

出版商:Blackwell Publishing Ltd    

年代:1983

数据来源: WILEY