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L J Lesko J R Benotti J S Alpert P M Brady J E McCue B H Weiner I S Ockene 《Journal of pharmaceutical sciences》1986,75(10):952-954
The pharmacokinetics of intravenous bepridil (1-[2-(N-benzylanilino)-1-(isobutoxymethyl)ethyl]pyrrolidine ) were studied in 16 patients undergoing cardiac catheterization for evaluation of coronary disease, all with normal base-line hemodynamic and renal functions. Ten patients received 3 mg/kg and six patients received 4 mg/kg of bepridil infused over a period of 30 min. Plasma bepridil concentrations were measured by HPLC and analyzed by model-dependent and model-independent methods. The mean (+/- SD) maximum plasma bepridil concentrations at the end of the infusion were 2047 +/- 820 ng/mL (3 mg/kg) and 2478 +/- 1426 ng/mL (4 mg/kg). Postinfusion bepridil concentrations were best described by a two-compartment open model. The model-dependent harmonic mean distribution and elimination half-lives were 1.7 h (range: 1.1-2.2 h) and 19.7 h (range: 8.0-61.9 h), respectively. The harmonic mean elimination half-life from model-independent analysis was 14.9 h (range: 7.4-64.0 h). The arithmetic means of other model-independent kinetic parameters were systemic clearance, 0.524 +/- 0.215 L X kg-1 X h-1; Vd, 15.3 +/- 10.9 L/kg; and Vdss, 10.1 +/- 6.0 L/kg. Model-dependent and model-independent estimates of half-life and clearance agreed reasonably well. Bepridil was well tolerated, effecting little or no change in central hemodynamics or EKG intervals. The extensive distribution and relatively slow clearance of bepridil account for its long elimination half-life. Intravenous bepridil appears to be a safe calcium (II) antagonist that is suitable for once-a-day dosing. 相似文献
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CM Reid M. Nelson P. Beckinsale P. Ryan LMH Wing LJ Beilin MA Brown GLR Jennings CI Johnston J. Marley JJ McNeil TO Morgan J. Shaw ID Steven MJ West 《Clinical and experimental pharmacology & physiology》1997,24(5):370-373
1. The present study aimed to determine the feasibility of conducting a 5 year cardiovascular outcome trial of the treatment of 6000 elderly hypertensive patients in Australian general practices. 2. General practitioners (GPs) were invited to participate by mail and personal follow-up. Patient records were reviewed to identify subjects for a blood pressure (BP) screening programme. Blood pressure was measured on three occasions and eligible subjects were included if the average BP was 160 mmHg systolic or 90 mmHg diastolic if systolic BP was 140 mmHg. 3. Seven hundred and forty-one GPs were approached and 89 were enrolled in the study (12% of mail invites and 75% of those receiving a personal contact). In 16 practices where screening was completed, 82 000 records were reviewed to identify 4% patients eligible for screening. Twenty-two per cent of eligible subjects attended screening. Of 1938 subjects screened, 180 (9%) had BP 5=160/90 mmHg. Forty-seven percent of subjects (n = 916) were receiving antihypertensive therapy and 184 (20%) were withdrawn from therapy. One hundred and sixteen (63%) of these subjects had BP return to study entry levels within 6 weeks. Fifty-seven newly diagnosed and 81 previously treated subjects were randomized (7% of the screened population). 4. Based on the high participation rate of GPs, the response rate of patients to attend a BP screening programme and the 7% randomization to screening ratio for entry into the study, the ANBP2 pilot study has demonstrated that it is feasible to recruit subjects from Australian general practices to a cardiovascular outcome trial. 相似文献
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This paper reviews the clinical aspects of depression in cancer from the perspective of prevalence, diagnosis, clinical symptoms, classification and treatment. Clinical trials, reported since 1960, of psychosocial, psychopharmacologic and behavioral interventions are critically evaluated. Therapeutic guidelines are offered for the management of the depressed patients with cancer. Research directions are suggested for the future. 相似文献
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BACKGROUND: The recent introduction of urea sensors for dialysis monitoring
has made possible new approaches to urea kinetic modelling. In this study
we show how the equilibrated postdialysis urea concentration (Ceq) and Kt/V
corrected for double-pool urea kinetics (Kt/Vdp) can be accurately
determined using an on-line sensor providing a continuous measure of blood
water urea. A modification of the Smye constant volume double-pool theory
led to the following equations for Ceq and Kt/Vdp [formula: see text] where
Cpre is the blood concentration measured at the start of dialysis, t is the
length of the dialysis session (in min) and S(ex) is the constant slope of
the blood urea logarithm concentration decline following development of the
intercompartmental urea concentration gradient in the first 30-60 min of
dialysis. METHODS: These equations were tested in 11 patients undergoing
165-240 min of paired filtration dialysis with continuous monitoring of
blood urea concentration. Cpre was determined as the plateau concentration
during a preliminary period of 15-20 min of slow isolated ultrafiltration.
S(ex) was accurately determined from linear regression applied to the urea
sensor data from the 80-min point to the end of dialysis. RESULTS: Ceq and
Kt/Vdp determined from the above equations compared closely to values
determined from 25-40 min of urea rebound monitoring with the urea sensor:
10.6 +/- 3.0 versus 10.8 +/- 2.7 mmol/l (mean +/- SD) for Ceq and 1.21 +/-
0.24 versus 1.18 +/- 0.20 for Kt/Vdp, compared to single-pool values of
Kt/V = 1.34 +/- 0.23. CONCLUSION: This technique may be readily programmed
into on-line urea monitors to provide current and extrapolated values of
Ceq and Kt/Vdp from about the first hour of dialysis.
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Zhao P Qin ZL Ke JS Lu Y Liu M Pan W Zhao LJ Cao J Qi ZT 《第二军医大学学报》2005,26(10):1167-1167
SARS-CoV isa newly identified coronavirus that causes severe acute respiratory syndrome (SARS). Currently, there is no effective method available for prophylaxis and treatment of SARS-CoVinfections. In the present study, the influence of small interfering RNA (siRNA) on SARS-CoV nucleocapsid (N) protein expression was detected in cultured cells and mouse muscles. Four siRNA expression cassettes driven by mouse U6 promoter targeting SARS-CoV N gene were prepared, and their inhibitory effects on expression of N and enhanced green fluorescence protein (EGFP) fusion protein were observed. 相似文献