ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1982.tb02675.x

出版商:Blackwell Publishing Ltd    

年代:1982

数据来源: WILEY

摘要:

Abstract:Eight patients with essential hypertension completed a double‐blind, randomly allocated crossover comparison of either 5 or 10 mg enalapril maleate, 50 mg hydrochlorothiazide, or their combination administered once daily during sequential two‐week periods. Blood pressure, pulse rate, plasma renin activity, angiotensin‐converting enzyme activity, plasma aldosterone concentration, and urinary electrolytes were monitored for 24 hours after placebo and on days 1 and 14 of each treatment period. After two weeks of each treatment, only the combination of enalapril and hydrochlorothiazide significantly lowered the mean seated diastolic blood pressure (SDBP). Likewise, SDBP control (≤ 90 mm Hg) was achieved only after combination therapy; six of the eight patients were controlled by the combination for up to 24 hours. The initial SDBP response to combination therapy differed with the sequence of drug addition; however, by day 14 the responses were comparable, regardless of whether hydrochlorothiazide or enalapril was first given. Mean converting enzyme activity was suppressed by enalapril in all patients, though it did not always correlate with changes in SDBP or plasma aldosterone. Mean plasma renin activity increased, but the increase was significant only on the combination. There were no serious adverse

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1982.tb02676.x

出版商:Blackwell Publishing Ltd    

年代:1982

数据来源: WILEY

摘要:

Abstract:The short‐term hypnotic efficacy of 15 mg flurazepam was evaluated in nine patients (mean age 37.2 ± 15.9 years) who complained of insomnia and had polysomnographic evidence of disturbed sleep. Patients slept in the laboratory 14 consecutive nights, and their sleep was monitored using standard polysomnographic procedures. Prior to bedtime, they received a placebo the first four nights, 15 mg flurazepam on nights 5 through 11, and a placebo again on nights 12 through 14. Flurazepam significantly increased total sleep time while reducing the latency to stage 1 sleep, the number of awakenings in the night, and the amount of wakefulness after sleep onset. Sleep stage patterns also were altered significantly with flurazepam: percentage stage 2 sleep increased, and percentages of stage 3–4 sleep and REM sleep (on drug night 1 and nights 1–3) decreased. With the exception of REM sleep, most of these drug effects were first detected on the second night of administration, did not diminish over the next six nights, and persisted during the three‐day withdrawal period. Subjective evaluations of sleep generally corresponded with the polysomnographic data. It was concluded that 15 mg flurazepam has significant hypnotic properties with minimal adverse side

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1982.tb02677.x

出版商:Blackwell Publishing Ltd    

年代:1982

数据来源: WILEY

摘要:

Abstract:Mixtures of antituberculosis drugs were evaluated for their in vitro effects on drug‐resistant isolates ofMycobacterium tuberculosisandM. avium‐intracellulare. The response of individual isolates to representative drug combinations was not always predictable from the results of single‐drug sensitivity assays. For the case ofM. tuberculosis, combinations of drugs were often bactericidal even under conditions where two or more drugs were without effect when tested singly. The more widely drug‐resistantM. avium‐intracellularedemonstrated increased growth inhibition when subcultured in the presence of single drugs, particularly rifampin and streptomycin. However, these conditions favored the selection of highly resistant strains. Alternatively, multiple drugs were often bacteriostatic; and under conditions where isolates demonstrated growth inhibition, the selection of highly drug‐resistant strains was delayed. These results suggest a role for multiple‐drug sensitivity assays in selecting drug combinations to be used in the treatment of drug‐resistant

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1982.tb02678.x

出版商:Blackwell Publishing Ltd    

年代:1982

数据来源: WILEY

摘要:

Abstract:The hemodialyzability of primidone was investigated in four patients on long‐term hemodialysis. Primidone, 500 or 250 mg, was given orally 2 hours before hemodialysis. Blood and dialyzate samples were collected periodically during the 4‐hour dialysis and measured by gas‐liquid chromatography and high‐performance liquid chromatography for primidone. Dialysis clearance calculated by the instantaneous dialyzate method averaged 97.7 ml/min, which is considerably greater than the metabolic clearance of 30 ml/min for the drug. The extraction efficiency of the hollow‐fiber dialyzers averaged 40.2 per cent for plasma samples. A mean of 31.7 per cent of the administered dose of primidone was removed during hemodialysis. The half‐life was 5.1 hours in our patients during hemodialysis, a nearly two‐thirds reduction of the 13.9‐hour half‐life calculated in uremic patients. Because of the reduction in elimination half‐life, greater dialysis clearance than metabolic clearance, high extraction efficiency, and significant drug removal during dialysis, we conclude that prim

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1982.tb02679.x

出版商:Blackwell Publishing Ltd    

年代:1982

数据来源: WILEY

摘要:

Abstract:Stable isotope labeling of drugs has been used in human metabolism studies because it eliminates the risk of radiation exposure accompanying use of radioactive tracers. The labeled drug can be measured by gas‐chromatographic mass spectrometry (GCMS). However, if reliable pharmacokinetic data are to be obtained, one has to be certain the rate of metabolism of labeled and unlabeled drug is the same, i.e., there is no kinetic isotope effect. To evaluate this for phenobarbital (PB), three humans were infused with a 1:1 mixture of phenobarbital and 1,3‐15N2‐2‐13C‐PB. Serum was collected at regular intervals. Concentrations of labeled and unlabeled phenobarbital were determined by GCMS. Within each subject, there was no trend for concentrations of labeled phenobarbital to be higher or lower than concentrations of unlabeled phenobarbital (P>0.90 for all three subjects). There was no difference in the zero time intercepts, distribution and elimination time constants and half‐lives, volumes of distribution and central compartment, or clearance of the two forms of phenobarbital. Thus, no isotope effect was found. Published data on other labeled drugs and the likelihood of encountering an isotope effect based on type of isotope and its location in the molecule ar

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1982.tb02680.x

出版商:Blackwell Publishing Ltd    

年代:1982

数据来源: WILEY

摘要:

Abstract:Plasma concentrations of minaxolone were measured in 15 female patients during and for up to 3 hours after a minaxolone and nitrous oxide anesthetic. Nine patients received a single dose and six patients two or three doses of minaxolone. Plasma minaxolone decay can be described by two‐compartment kinetics. Distribution is rapid, with a mean half‐life of 2.1 minutes, and the elimination half‐life is short (47 minutes). Plasma clearance is high (1.55 l./min). Plasma levels of minaxolone at recovery were similar in patients receiving both single and multiple doses, suggesting a valid relationship between plasma level and effect. It is suggested that minaxolone may be a suitable agent for administration by continuous inf

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1982.tb02681.x

出版商:Blackwell Publishing Ltd    

年代:1982

数据来源: WILEY

摘要:

Abstract:The objective of this study was to compare the pharmacokinetic behavior of erythromycin in normal volunteers with that in subjects with alcoholic liver disease. Six normal volunteers received 500 mg erythromycin as an intravenous infusion or as two 250‐mg enteric‐coated tablets in a crossover fashion. The pharmacokinetics of erythromycin after intravenous administration was best described as a two‐compartment model. The elimination half‐life was 1.6 ± 0.7 hours (mean ± S.D.) after the intravenous dose and 2.0 ± 0.7 hours after the oral dose. In patients with alcoholic liver disease the elimination half‐life after oral administration of two 250‐mg enteric‐coated tablets was 3.2 ± 0.5 hours, significantly different from that in normal subjects, probably due to impaired metabolism. The difference in half‐life does not require dosage adjustment in this patient population. The systemic availability of erythromycin was 33.5 per cent (range 10.

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1982.tb02682.x

出版商:Blackwell Publishing Ltd    

年代:1982

数据来源: WILEY

摘要:

Abstract:A method is described which estimates one‐compartment linear pharmacokinetic parameters from two serum drug concentrations obtained at any known times during a drug regimen. During multidose regimens, these two samples need not have a specific temporal relationship to a particular dose. Also, the method will predict eventual steady‐state drug concentrations early in the course of a continuous infusion. Modifications of the basic method will accommodate variations in the dosage regimen and permit the analysis of data in patients who have measurable serum drug concentrations prior to the start of the regi

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1982.tb02683.x

出版商:Blackwell Publishing Ltd    

年代:1982

数据来源: WILEY