ISSN:1075-2765    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Nifedipine, 10-mg capsules, were given orally and sublingually to six healthy volunteers according to a randomized crossover design. Nifedipine plasma levels, blood pressure, and heart rate were determined at several times after medication. Cmaxwas higher (134 ± 17 vs. 93 ± 2 ngml-1, mean ± SD, P < 0.01) and occurred earlier (0.5 vs. 1 h) with oral than with sublingual nifedipine. However, there was no significant difference in AUC (268 ± 56 vs. 288 ± 35 ng h ml-1) nor in f1/2 (1.8 ± 0.2 vs. 1.9 ± 0.3 h), indicating that sublingual administration decreased the rate but not the extent of nifedipine absorption. Notwithstanding the difference in Cmax, both routes yielded a similar reduction in diastolic blood pressure of 13 ± 1 mm Hg. Heart rate increase, which reflects the activation of homeostatic mechanisms, was greater with oral than with sublingual nifedipine, that is, 18 ± 1 vs. 13 ± 1 beats min1, P < 0.01. It is concluded that slower absorption after sublingual administration increases nifedipine hypotensive efficiency by producing less counteracting homeostatic responses than the more rapidly absorbed oral nifedipine.

ISSN:1075-2765    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

In patients with essential hypertension, increased level of platelet activity expressed as the concentrations of p-thromboglobulin (β-TG) and platelet factor 4 (PF4) were observed. Elevation of the levels of both β-TG and PF4 correlated with the increase in platelet aggregability in platelet-rich plasma (PRP) and the decrease in red blood cell deformability, which were considered as being the possible factors for the platelet intravascular activation. After 2 weeks of monotherapy with nifedipine (40 mg daily), a decrease in platelet aggregability in PRP was observed in 35 of the 75 patients and an increase in red cell deformability in 37 of the 75 patients. Using cluster analysis, all cases were divided into several groups based on nifedipine effects on red cell deformability and platelet aggregability in PRP. It was revealed that the statistically significant decrease in the levels of platelet markers took place only in patients in whom nifedipine simultaneously decreased platelet aggregability and increased red cell deformability. Analysis of variance showed a high power of influence for combined changes in these parameters for reducing intravascular platelet activation by nifedipine. It is suggested that nifedipine reduces platelet activity by direct action on platelets and indirectly due to its capacity to increase red cell deformability, resulting in elimination of platelet stimulation by red blood cells.

ISSN:1075-2765    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

The pharmacokinetics of a controlled-release formulation (coat-core) of the calcium channel blocker nisoldipine was investigated in eight subjects with biopsy-proved liver cirrhosis and eight healthy subjects. In Stage I, subjects received a single 10-mg dose to determine if this dose would be safely tolerated in the subjects with cirrhosis. Because all subjects in both groups tolerated the dose without difficulty, all were continued to Stage II. In Stage II, subjects received a once-daily dose of 10-mg coat-core tablets for 7 days. Serial plasma samples were assayed for nisoldipine in both stages. The Cmaxand AUC of nisoldipine were approximately fourfold to fivefold higher (p < 0.01) in subjects with cirrhosis as compared to healthy subjects; however, there was overlap in the range of pharmacokinetic parameters between the two groups. The accumulation factor following multiple dosing was similar in both groups. Results suggest that nisoldipine dose should be optimized by monitoring of a pharmacodynamic end point, such as effect on blood pressure. It is likely that dose requirements for patients with liver disease will be lower.

ISSN:1075-2765    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

The objective of this investigation was to compare the single-dose and steady-state pharmacokinetic profiles of Dilacor XR to Cardizem CD. The study enrolled 24 healthy males and was divided into three parts: a single intravenous 25-mg bolus dose of diltiazem HC1 (Cardizem Injectable) followed by a two-way crossover comparison of single and multiple once-daily 240-mg oral doses of Dilacor XR and Cardizem CD. Plasma samples were analyzed for diltiazem using a specific and sensitive HPLC assay. Statistical analysis and deconvolution were performed on the data. A 1− and 3-hour lag time in diltiazem absorption was noted following the administration of Dilacor XR and Cardizem CD, respectively. Statistically significant differences were noted in mean single- and multiple-dosetmaxvalues with Cardizem CD taking approximately twice as long as Dilacor XR to reach Cmax. Dilacor XR was equivalent to Cardizem CD with respect to AUC(0−X)and Cmax. Equivalent minimum and average steady-state plasma diltiazem concentrations were noted after multiple-dose administration. Deconvolution of the single-dose data also showed similar mean bioavailabilities for the respective formulations but revealed dissimilarities in each product's absorption profile that may reflect observed differences in absorption lag time andtmax.

ISSN:1075-2765    

出版商:OVID    

年代:1995

数据来源: OVID

ISSN:1075-2765    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

ObjectivesTo assess the antianginal and antiischemic efficacy, safety, and the potential for tolerance or withdrawal effects of amlodipine.BackgroundThe slow onset of action and long half-life of amlodipine may help avoid withdrawal effects such as the exacerbation of angina and precipitation of myocardial infarction seen with β-blockers.MethodsAfter a 2-week single-blind placebo run-in period, 226 patients with stable exertional angina pectoris were given amlodipine (starting at 5 mgday−1and titrated to 10 mgday1) in a single-blind fashion for 8 weeks. One hundred seventy-two responders (≥7% improvement in symptom-limited exercise time) entered a 4-week double-blind withdrawal phase and randomly received continued treatment with amlodipine (n=91) or placebo (n= 81).ResultsTreatment with amlodipine increased the exercise capacity by 14% and improved time to angina onset by 25% and time to 1-mm ST segment deviation by 18%. These variables remained essentially unchanged at the end of the 4-week withdrawal phase for the group continued on amlodipine (+0.8%, +3.2%, and +2.0%, respectively) but decreased for the group on placebo (−5.8%, −9.8%, and −11.0%, respectively) (p< 0.001 between groups, all assessments) to values similar to those obtained during the initial placebo run-in period. Approximately one-third of the patients responded to 5 mg amlodipine during single-blind therapy and according to “usual clinical practice‘’ remained on this dose. The results of randomized withdrawal in the subgroup receiving 5 mg also favored amlodipine over placebo. Side effects were reported by 47% of patients on amlodipine and by 22% of patients receiving placebo. The most frequently reported side effects for ….

ISSN:1075-2765    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

With the aim of verifying the effect of omeprazole treatment on theophylline serum concentration in elderly peptic ulcer patients, we studied 10 male subjects aged > 65 years (mean age = 75.2, range = 67–86) with chronic obstructive bronchopneumonia and endoscopically diagnosed duodenal ulcer in acute phase. All subjects were treated with a slow-release formulation of theophylline 200 mg b.i.d. plus omeprazole 20 mg daily for 4 weeks. In all subjects serum concentrations of azote, creatinine, theophylline were determined at the beginning and after 1 and 4 weeks; at the beginning and end of the study, pepsinogen group A (PGA), pepsinogen group C(PGC) and gastrin were measured. Statistical analysis was performed with the Student's f-test for paired data.The results showed no statistically significant differences after 1 and 4 weeks of omeprazole treatment in serum concentration of theophylline (T0= 7.4, T1week = 7.5, T4weeks = 6.0, p = ns), azote (T0= 45.2, T1week = 30.5, T4weeks = 36.1, p = ns), creatinine (T0= 1.27, T1, week = 1.02, T4weeks = 1.16,p= ns), PGA (T0= 99.5, T4weeks, = 126.2,p= ns), and PGC (T0= 10.6, T4weeks = 12.1,p= ns); however serum gastrin increased from T0= 70.2 ± 13.2 to T4weeks = 130.3 ± 18.3 (p< 0.0001). It was concluded that (1) serum concentration of theophylline is not affected by the concomitant omeprazole treatment lasting 1 month in elderly patients suffering from chronic obstructive bronchopneumonia and peptic ulcer, (2) modifications of dosages of theophylline and/or omeprazole are not necessary in the elderly with normal renal function, (3) the increase in fasting serum gastrin after 4 weeks of treatment may indicate that omeprazole 20 mg daily is efficacious in inhibiting gastric acid secretion in the elderly people.

ISSN:1075-2765    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Acetohexamide, an oral antidiabetic agent, is metabolized by carbonyl reductase to hydroxyhexamide, which has a higher hypoglycemic potency than the parent compound. In the present study, interindividual variability of carbonyl reductase activity in erythrocyte was examined. Enzyme activity in 31 healthy subjects (23.9 ± 3.4 years, mean ± SD) was monitored by measuring formation of hydroxyhexamide using HPLC methods. Using 0.5 mM acetohexamide as substrate, reductase activity of 6.06 ± 0.06 nmol min1gHb−1(range: 5.9–6.2) with a coefficient of variation of 15% was observed in erythrocytes. Acetohexamide-reducing activity in erythrocytes showed a normal distribution and the interindividual variability of the reductase activity was found to be small, implying that the large variability reported for the acetohexamide plasma half-life is not caused by the amount of reductase enzyme in erythrocytes.

ISSN:1075-2765    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Nonequilibrium distribution of ethanol in the total body water (TBW) has implications for understanding gross intoxication seen after rapid consumption of alcohol and for certain new clinical monitoring methods where ethanol is used as a tracer. We studied the rate of distribution of ethanol into the TBW from the concentration-time profiles in whole blood after 0.4 g kg−1of ethanol was given by intravenous infusion over 15, 30, 45, and 60 min to six female volunteers. We also gave these females 0.6 gkg−1over 30 min, and five young males 0.4 gkg−1over 30 min. The results suggest that the blood ethanol concentration after rapid infusion can be described by a two-compartment model with first-order distribution kinetics and zero-order (saturated Michaelis-Menten) elimination. Distribution of ethanol occurred with a half-time of 6.6 ± 2.6 min (mean ± SD). Alcohol intoxication was more pronounced when ethanol was given rapidly. We conclude that predictable differences in the concentration of ethanol between the blood and the peripheral tissues during rapid supplementation of ethanol causes higher concentrations in blood and a more pronounced intoxication.

ISSN:1075-2765    

出版商:OVID    

年代:1995

数据来源: OVID