摘要:

Amdinocillin is a novel penicillin whose antibacterial activity is derived from its ability to bind specifically and avidly to Penicillin Binding Protein‐2 (PBP 2). Other β‐lactams bind almost exclusively to PBPs 1 and 3. This unique feature has prompted many investigators to predict that amdinocillin would aggressively synergize with other antimicrobials, particularly other β‐lactams. Certain features of these predictions have been realized.Amdinocillin is active alone against many gram‐negative organisms. Pseudomonas and non‐fermenting gram‐negative bacteria, however, are usually resistant. Amdinocillin, in combination with many β‐lactams, exhibits marked synergy against many enterobacteriaceae. No such synergy can be demonstrated for gram‐positive organisms or pseudomonas species. Amdinocillin is not β‐lactamase stable. Organisms which produce high levels of plasma‐mediated β‐lactamase are resistant to the drug.Amdinocillin is widely distributed to most tissues of the body. It is removed by renal tubular secretion which results in prodigious levels of the drug in the urine. Coadministration of probenecid results in markedly elevated plasma levels of amidinocillin and delays its excretion. Amdinocillin has a plasma half‐life of about one hour in patients with grossly normal renal function. Its half‐life increases to 3 to 6 hours in anephric patients. The spectrum of adverse reactions observed with amdinocillin is similar to that of other penicillins.Amdinocillin, as a single agent, is effective in the treatment of urinary tract infections caused by susceptible strains of E. coli and klebsiella and enterobacter species. When amdinocillin is used in concert with other antimicrobials, synergy can frequently be demonstrated but it is essentially limited to gram‐negative aerobic organisms. At present, insufficient data are available to precisely profile the utility of amdinocillin, either alone or in combination, in the

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1985.tb04448.x

出版商:Blackwell Publishing Ltd    

年代:1985

数据来源: WILEY

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1985.tb04449.x

出版商:Blackwell Publishing Ltd    

年代:1985

数据来源: WILEY

摘要:

The kinetics ofN‐acetylprocainamide (NAPA) were studied in 5 patients (all men, mean age = 62) with coronary artery disease and ventricular arrhythmias during loading infusions of 0.22–0.45 mg/kg/min, prolonged (19–48 hrs) intravenous infusions 2.5–5.2 mg/min, and in 4 of the patients, during subsequent oral doses 1.5–3 g every 8 hrs. Serum, concentrations of NAPA were determined by high‐performance liquid chromatography. The individual concentration‐time profiles could, with one exception, be described by a two‐compartment, open, kinetic model with apparent first‐order elimination. The kinetic variables were: initial distribution volume (Vc) 0.20 ± 0.11 l/kg (mean ± SD); steady‐state distribution volume (Vss) 1.58 ± 0.55 l/kg; distributional clearance (Cle) 133 ± 23 ml/(kg·hr); absorption rate constant (Ka) 0.354 ± 0.173 hr−1; and fraction of dose reaching systemic circulation (F) 1.00 ± 0.14. The data for one patient who had received increasing oral dosages of 1.5, 2, 2.5 and 3 g every 8 hours resulted in systematic underprediction of observed concentrations at the two highest oral dosing rates. This suggests the possibility of some degree of nonlinearity or time‐dependent change in the kinetic behavior of NAPA. Only low concentrations of procainamide,<1 mg/L, were fou

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1985.tb04450.x

出版商:Blackwell Publishing Ltd    

年代:1985

数据来源: WILEY

摘要:

The effects of two histamine 2‐receptor antagonists, cimetidine and ranitidine, on the single‐dose pharmacokinetics of diltiazem were studied in 6 healthy subjects. A single 60‐mg oral dose of diltiazem was administered alone, after ranitidine 150 mg twice daily for 7 days, and after cimetidine 300 mg 4 times a day for 7 days. Plasma samples were obtained over a 10‐hour period and analyzed for the parent drug and one of its metabolites, deacetyldiltiazem (DAD). Concurrent cimetidine produced a significant (p<0.05) increase in diltiazem levels at most time points, in peak concentration and area under the concentration‐time curve. These variables were also increased during concurrent ranitidine administration but did not reach statistical significance. The DAD plasma concentration was below measurable levels during the control phase but increased during concurrent cimetidine and ranitidine administration. Caution should be exercised when diltiazem is administered concurrently with cimetidine and possibly, r

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1985.tb04451.x

出版商:Blackwell Publishing Ltd    

年代:1985

数据来源: WILEY

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1985.tb04452.x

出版商:Blackwell Publishing Ltd    

年代:1985

数据来源: WILEY

摘要:

A clear understanding of the pharmacokinetics of a drug and of the proper methods for calculating dialyzer clearance is essential in designing hemodialysis studies. Hemodialysis should not begin until drug distribution is complete. Institution of dialysis prior to distribution equilibrium will result in increased removal of drug compared to what would be found in the clinical setting. All methods of calculating dialyzer clearance should be compared to that using total amount of drug recovered in the bath divided by the area under the drug concentration versus time curve during dialysis. To adequately probe the effect of the artificial kidney on drug concentrations sufficient plasma samples must be drawn postdialysis to define the rebound phenomena.

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1985.tb04453.x

出版商:Blackwell Publishing Ltd    

年代:1985

数据来源: WILEY

摘要:

We reviewed 103 controlled clinical trials that compared the antiarthritic efficacy and tolerance of previously and currently marketed nonsteroidal antiinflammatory drugs (NSAIDs) and aspirin. Of 52 studies, 35 had data sufficient to calculate an NSAID efficacy index (the ratio of mean improvement in NSAID‐treated patients to that in aspirin‐treated patients) based on subjective and/or objective criteria. The mean indexes (obtained from all studies from which an index could be calculated) indicated no statistically significant difference in efficacy between aspirin and the NSAIDs as a group; the indexes tended to become less variable as the number of study subjects increased. Tolerance, assessed from the percentage of patients who discontinued the drug because of side effects, was significantly greater for NSAIDs than for aspirin. The NSAIDs had greater efficacy but not greater toxicity at increased doses. Efficacy differences described among NSAIDs in some studies were attributable either to comparisons at nonequivalent doses or to cha

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1985.tb04454.x

出版商:Blackwell Publishing Ltd    

年代:1985

数据来源: WILEY

摘要:

Book reviewed in this article:Pain, Analgesia, and Addiction: The Pharmacologic Treatment of Pain, by Barry Stimmel.Therapeutics in Terminal Cancer, by Robert G. Twycross and Sylvia A. Lack.Antacids and Other Drugs in GI Diseases, by W.A. Ritschel.Psychiatric Medicine Update: Massachusetts General Hospital Reviews for Physicians, 1984 edition. Edited by Theo C. Manschreck and George B. Murray.

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1985.tb04455.x

出版商:Blackwell Publishing Ltd    

年代:1985

数据来源: WILEY

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1985.tb04457.x

出版商:Blackwell Publishing Ltd    

年代:1985

数据来源: WILEY

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1985.tb04458.x

出版商:Blackwell Publishing Ltd    

年代:1985

数据来源: WILEY