ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1982.tb02642.x

出版商:Blackwell Publishing Ltd    

年代:1982

数据来源: WILEY

摘要:

Abstract:Amiloride is a potassium‐sparing diuretic which has been advocated for the treatment of hypokalemic disorders. This agent was prospectively evaluated in hypokalemic patients with either primary hyperaldosteronism (ten patients) or Bartter's syndrome (five patients). Vital signs, electrolytes, and ambulatory hormonal studies were assessed during a control period and treatment period with amiloride therapy at 10 to 40 mg/day over two to 24 weeks. During the treatment period the systolic and diastolic blood pressure fell significantly in primary hyperaldosteronism but remained unchanged in Bartter's syndrome. In summary, amiloride therapy (1) increased plasma potassium in both diseases; (2) increased plasma renin activity (PRA) in primary hyperaldosteronism but decreased PRA in Bartter's syndrome; and (3) increased plasma aldosterone in both diseases. Since potassium is known to suppress renin production and stimulate aldosterone secretion, correction of the hypokalemia in this study probably accounts for the decreased PRA and increased plasma aldosterone observed in Bartter's syndrome. The increase in both PRA and plasma aldosterone in primary hyperaldosteronism, however, may be evidence of either a direct activation of the renin‐aldosterone system or, alternatively, may be due to the mild natriuretic effects of amilor

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1982.tb02643.x

出版商:Blackwell Publishing Ltd    

年代:1982

数据来源: WILEY

摘要:

Abstract:Thirty‐eight ambulatory patients with congestive cardiac failure took part in a double‐blind clinical trial of 50 mg hydrochlorothiazide orally daily and slow‐release formulation of 60 mg furosemide orally daily. Following a one‐week period of placebo administration, patients were randomly allocated to the treatment which they continued for six weeks. Other diuretic drugs were discontinued at entry, but antihypertensive drugs and digoxin were continued during the study at constant dosage. A controlled sodium diet was prescribed. Clinical observations and biochemical and hematologic measurements were made before, during, and at the end of the study. There was an improvement in the clinical condition of patients in both treatment groups, but no significant difference between treatments (with or without digitalis) was detected. Both treatments were clinically well tolerated; however, the tendency of hypokalemia was more pronounced in the hydrochlorothiazide group. This could be hazardous in patients who receive a concomitant cardiac glycoside, especially when no clear‐cut benefit of concomitant digitalis therapy is dem

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1982.tb02644.x

出版商:Blackwell Publishing Ltd    

年代:1982

数据来源: WILEY

摘要:

Abstract:Lormetazepam, an investigational hypnotic, was evaluated for efficacy and withdrawal phenomena in doses of 0.5, 1.0, 1.5, and 2.0 mg in four separate sleep laboratory protocols, each including four placebo baseline nights, seven drug nights, and three placebo withdrawal nights. A moderate degree of efficacy was shown across the four doses, but this was quite variable. There was no dose—response effect for efficacy for either the first three or last three nights of this short‐term administration period. In general, there was less efficacy on the later drug nights, indicating a potential for the development of tolerance over a relatively short period of time. Following drug withdrawal, there was a dose‐related worsening of sleep above baseline levels (rebound insomnia). The peak degree of worsening of sleep following drug withdrawal was more than two times greater than the peak degree of improvement of sleep with drug administr

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1982.tb02645.x

出版商:Blackwell Publishing Ltd    

年代:1982

数据来源: WILEY

摘要:

Abstract:An analysis was made of data from over 4000 postepisiotomy, uterine cramping, and postsurgical patients complaining of moderate or severe pain. They had received 325, 650, or 1300 mg aspirin or placebo while they were subjects in 10 analgesic clinical trials. On the average, for the same verbally expressed pain intensity level and the same treatment, more relief was obtained by a patient with uterine cramping than one with episiotomy pain, who in turn obtained more relief than a patient with surgical pain. A new mathematical model which characterizes the probability that an analgesic provides complete relief as a function of dose, severity of pain intensity, and pain etiology is developed. The model utilizes the data itself to estimate the numerical score corresponding to verbal pain intensities. The results indicate that the numerical score quantifying severe surgical pain is 1.4 times greater than the score for severe episiotomy pain, which in turn is 3.2 times greater than the score for severe uterine cramping. Clinical trials must be designed to take these differences into account. Also, clinicians must be cognizant of such differences when choosing among drugs and dosages for patients with different pain intensity and etiology.

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1982.tb02646.x

出版商:Blackwell Publishing Ltd    

年代:1982

数据来源: WILEY

摘要:

Abstract:The ability to precisely predict serum digoxin concentrations using 12 published methods in a group of 85 patients was undertaken. Two methods of estimating creatinine clearance and two estimates of ideal body weight were employed as input variables using the 12 dosing methods. This resulted in 40 relationships from which correlation coefficients and linear regression constants were derived for predicted versus measured serum digoxin concentrations. The correlation coefficients between predicted and measured serum digoxin ranged from −0.393 to 0.389. Possible explanations for the low correlation coefficients are interpatient variability in the kinetics of digoxin, the small number of subjects used to generate some of the digoxin dosing methods, undetected patient noncompliance in the present study, the use of empirically derived dosing methods, and/or the use of rather homogeneous patient populations to develop a given method while this study is comprised of a heterogeneous group of patients. The methods studied tend to overpredict serum digoxin concentrations and therefore generally allow safe, first approximations for digoxin dosin

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1982.tb02647.x

出版商:Blackwell Publishing Ltd    

年代:1982

数据来源: WILEY

摘要:

Abstract:We evaluated the protein binding and comparative bilirubin displacing properties of bumetanide and furosemide in pooled adult and cord serum by ultrafiltration (UF), difference spectra (DS), and Sephadex Gel‐25 (SG‐25) filtration. By UF, bumetanide was found to be highly protein bound (96.7 per cent), similar to published data on furosemide (97.2 per cent). SG‐25 filtration and DS showed an equal shift to the left of the free bilirubin curve when bumetanide and furosemide were added to serum, in adult and cord, at equimolar concentrations and both shifted the free bilirubin curve equally. Bilirubin displacement was greater (P<0.001) in cord than in adult serum with both drugs. When “presumed therapeutic” plasma concentration of furosemide (1–2 mg/liter) and bumetanide (0.5 mg/liter) were compared, it was noted that bumetanide displaced significantly less (P<0.001) bilirubin from albumin in cord blood than furosemide. Hence, bumetanide displaces less bilirubin at “presumed therapeutic” plasma concentrations than furosemide, suggesting that it might be more prudent to use bumetanide in sick neonates with hyperbilirubinemia. Data also provide evidence that bilirubin displacement by both diuretics is greater in neonatal serum albumin th

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1982.tb02648.x

出版商:Blackwell Publishing Ltd    

年代:1982

数据来源: WILEY

摘要:

Abstract:Twelve normal volunteers were empanelled in an open‐label, three‐way crossover study to evaluate the influence of alcohol on the pharmacokinetics of controlled‐release diazepam capsules. Each volunteer received one 15‐mg diazepam controlled‐release capsule alone, concomitantly with alcohol or followed by alcohol 2 hours later. The mean plasma concentration—time profiles following both alcohol treatments were superimposable on the profile from the control. The mean plateau concentrations were observed to endure from 2 through 12 hours in all cases. The mean ± S.D. areas under the plasma concentration—time curves from time zero to infinity were similar indicating no difference in the extent of absorption of diazepam in the presence of alcohol. The harmonic mean elimination half‐lives were also similar. Overall, the pharmacokinetics and the release properties of control led‐release diazepam capsule were not influenced by alcohol in

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1982.tb02649.x

出版商:Blackwell Publishing Ltd    

年代:1982

数据来源: WILEY

摘要:

Abstract:Tinidazole is a potent nitroimidazole compound active against, and used to treat,Trichomonas vaginalisinfections in males and females. Speculation exists in the literature that observed differences in tinidazole plasma concentrations between males and females may be due to sex‐mediated pharmacokinetic differences. To investigate this phenomenon, a study was designed to determine the pharmacokinetics of tinidazole in male and female subjects. Six male and six female volunteers were each administered a single 2‐Gm oral dose of tinidazole. Plasma and urine samples, collected over a 72‐hour period, were assayed by a sensitive and specific HPLC assay. Results demonstrate a significant correlation between tinidazole oral plasma clearance and body weight and apparent volume of distribution of tinidazole and body weight for male and female subjects, respectively. There were no apparent sex‐mediated differences in weight‐normalized pharmacokinetic parameters as documented by statistically equivalent mean oral plasma clearances (36.1 and 35.4 ml/kg/hour), apparent volumes of distribution (0.65 and 0.63 liter/kg), and elimination half‐lives (12.3 and 12.3 hours, males and females, respectively). Mean area under the tinidazole plasma concentration‐versus‐time curve and mean peak plasma concentration of tinidazole were 1.3 times greater for females than for males, apparently due to the smaller mean body weight of females and consequently a 1.3 times greater administered dose to the females on

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1982.tb02650.x

出版商:Blackwell Publishing Ltd    

年代:1982

数据来源: WILEY

摘要:

Abstract:Twenty‐four healthy volunteers aged 22 to 78 years received 650‐mg doses of acetaminophen (AAP) on five separate occasions. The modes of administration were: intravenous AAP by 5‐minute infusion; oral AAP as two 325‐mg tablets in the fasting state; oral AAP 650 mg as an elixir preparation in the fasting state; tablets with food; and elixir with food. Plasma concentrations of AAP were determined by high‐pressure liquid chromatography for up to 12 hours after the dose. In both the young and the elderly groups, the four oral modes of administration were significantly different with respect to peak plasma concentration (P<0.001), time to peak plasma concentration (P<0.001), and systemic availability (P<0.01). Although food slowed the rate of absorption of both oral preparations, no significant difference in peak acetaminophen plasma concentration or time of peak concentration was observed as a function of age. Absolute systemic availability of elixir and tablets in the fasting state tended to be lower in the elderly subjects (P<0.05). However, when either preparation was coadministered with food, there were no differences between the two age groups. Thus, age as such does not appear to be a critical determinant in the design of oral acetaminophen dosage

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1982.tb02651.x

出版商:Blackwell Publishing Ltd    

年代:1982

数据来源: WILEY