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Biomedical subjects

K J Klamerus

Publications and source records attributed to K J Klamerus.

13 recordsLinked to original sources
PubMed1996

Disposition of intravenous amiodarone in subjects with normal and impaired renal function.

In a study designed to determine the influence of renal dysfunction on the disposition of amiodarone and its metabolite, desethylamiodarone (DEA), 30 subjects received a single 5 mg/kg intravenous dose of amiodarone over 15 minutes. Of the 30, 11 had normal renal function (group I; mean +/- SD glomerular filtration rate [GFR] = 118 +/- 20 mL/min/1.73 m2), 9 had renal impairment (group II; GFR = 23 +/- 10 mL/min/1.73 m2), and 10 were long-term hemodialysis patients (group III; 4 of these patients were studied during dialysis). Total and free concentrations of amiodarone and DEA were measured by high-performance liquid chromatography. There were no significant differences between the three groups in mean systemic clearance, steady state volume of distribution, or mean residence time of amiodarone. However, the area under the concentration-time curve (AUC) for amiodarone was significantly higher in group I than in group II, and this finding was related to total body weight. Free fraction was similar in groups I and III. The disposition of amiodarone and its metabolite DEA was similar in patients with normal renal function, moderate renal dysfunction, and end-stage renal disease. Thus, dosage adjustment in patients with renal impairment is not necessary based on this pharmacokinetic analysis.

Adult↗
PubMed1996

Pharmacokinetics of intravenous amiodarone in patients with impaired left ventricular function.

To evaluate the potential need for modification of dose regimens of intravenous amiodarone in patients with left ventricular dysfunction, the pharmacokinetics of amiodarone and its active metabolite, desethylamiodarone (DEA), were examined after a single 15-minute intravenous infusion of amiodarone 5 mg/kg. Three parallel groups of otherwise healthy volunteers with normal (n = 12), moderately impaired (ejection fraction > 30 but < or = 45%; n = 6), or severely impaired (ejection fraction < or = 30%; n = 6) left ventricular function were enrolled in the study. Serial blood samples were obtained over a 76-day period for estimation of pharmacokinetic parameters. With the exception of the half-life (t1/2) of DEA, statistical comparisons revealed no significant between-group differences in pharmacokinetic parameters or correlations between pharmacokinetic parameters and ejection fractions. The t1/2 of DEA was increased by approximately 60% in patients with severe left ventricular dysfunction compared with that in patients with moderately impaired and normal left ventricular function. The rate of DEA formation is slow, however, and its concentration relative to amiodarone is low. Therefore, it is unlikely that concentrations of DEA in serum would reach levels that contribute significantly to the pharmacologic activity of amiodarone during short-term (up to 2 weeks) intravenous amiodarone therapy. Single doses of amiodarone were well tolerated. The results of this study suggest that intravenous amiodarone can be used with appropriate observation to control arrhythmias, regardless of the degree of left ventricular dysfunction.

Adult↗
PubMed1992

Introduction of a composite parameter to the pharmacokinetics of venlafaxine and its active O-desmethyl metabolite.

Venlafaxine is a structurally novel, nontricyclic compound that is being evaluated for the treatment of various depressive disorders. A randomized three-period crossover study was conducted to obtain pharmacokinetic and dose proportionality data on the drug and its active metabolite, O-desmethylvenlafaxine. Eighteen healthy young men received single doses of venlafaxine 25, 75, and 150 mg followed by 3 days of administration every 8 hours (q8h). Steady-state elimination half-life was 3 to 4 hours for venlafaxine and 10 hours for O-desmethylvenlafaxine; both were independent of dose. Venlafaxine had a high oral-dose clearance, ranging from 0.58 to 2.63 L/hr/kg across doses with the lowest mean clearance, 0.98 L/hr/kg, at the highest dose. The apparent clearance of O-desmethylvenlafaxine was lower than venlafaxine, ranging from 0.21 to 0.66 L/hr/kg, and the lowest mean clearance, 0.33 L/hr/kg, occurred at the lowest dose. The area under the metabolite curve was two to three times greater than that for venlafaxine. Each compound had linear dose proportionality up to 75 mg q8h. A composite parameter incorporating venlafaxine plus O-desmethylvenlafaxine was introduced (i.e., AUC [area under the curve] + activity factor.AUCm), which extended linearity to 150 mg q8h. In summary, venlafaxine is a high-clearance drug that forms a metabolite with almost equal activity and demonstrates linear dose-proportionality.

Adult↗
PubMed1990

Labetalol for the control of elevated blood pressure following coronary artery bypass grafting.

In a multicenter study, the efficacy and safety of intravenous (IV) labetalol for the control of elevated blood pressure were studied in the intensive care unit (ICU) in 65 patients within 4 hours following coronary artery bypass grafting (CABG). Patients with pre-existing ventricular dysfunction, bradycardia, bronchospastic disease, or postoperative complications were excluded. All patients were monitored with a thermodilution pulmonary artery catheter. Entry criteria were a systolic blood pressure (SBP) greater than 140 mm Hg or diastolic blood pressure (DBP) greater than 90 mm Hg for at least five minutes. Intravenous labetalol was loaded incrementally (5, 10, 20, and 40 mg at 10-minute intervals) to a maximum cumulative dose of 75 mg, until either SBP decreased 10% or DBP decreased 10% and was less than 90 mm Hg. Responders were entered into a 6-hour maintenance period, and received 5 to 40 mg of IV labetalol every 10 minutes as needed for blood pressure control. Hemodynamic data and temperature were recorded at baseline, just before each dose of labetalol during the loading period, and at the end of the maintenance period. Alternative therapy was given in the case of nonresponse or adverse events. Intravenous labetalol successfully controlled post-CABG hypertension in 55 of 65 patients (85%); of these, 46 responded to 35 mg or less. Although 28 patients required no further labetalol in the maintenance period, in the others dosage varied from 5 to 400 mg. Reductions in SBP and DBP were associated with moderate reductions in pulse pressure (SBP-DBP) and heart rate (HR). Cardiac index decreased by 18.5%, with a 12.5% decrease in stroke index and 8.1% decrease in HR. Systemic vascular resistance did not increase significantly. Four patients (6%) developed hypotension related to IV labetalol. There was one death due to perioperative myocardial infarction, which was unrelated to labetalol use. The mechanism of action of IV labetalol in controlling hypertension after CABG surgery seems to be moderate negative inotropy and chronotropy. Its alpha-blocking effects seem to be important in preventing reflex vasoconstriction. This is directly opposite to the primary vasodilator effect found when IV labetalol is used to control nonsurgical hypertension. Because of these actions, labetalol should be avoided or used with caution in patients with preoperative and postoperative cardiac dysfunction. In patients with normal left ventricular function, IV labetalol appears to be a safe, effective agent in controlling post-CABG hypertension, with the added potential benefit of enhanced myocardial oxygen balance.

Analysis of Variance↗
PubMed1988

Effect of cardiopulmonary bypass on vancomycin and netilmicin disposition.

The effect of cardiopulmonary bypass (CPB) on the disposition of vancomycin (15 mg/kg) and of netilmicin (3 mg/kg) was studied in 10 adults. The concentration-time profile of the drug in serum and renal clearance were characterized pre-CPB, during CPB, and post-CPB. Vancomycin and netilmicin exhibited initial decreases in mean concentrations in serum of 4.0 mg/liter (16.8%) and 2.2 mg/liter (29.1%), respectively, upon initiation of CPB. Netilmicin concentrations in serum rebounded to a mean of 0.6 mg/liter (15.4%) within 90 min on CPB and then continuously decreased. Vancomycin concentrations in serum demonstrated a rebound increase of 2.3 mg/liter (23.5%) at the end of CPB when the aorta was unclamped. Mean renal clearance throughout CPB was decreased for vancomycin (58.4 to 43.4 ml/min per m2) and netilmicin (53.4 to 31.5 ml/min per m2). The rebound in vancomycin concentration in serum strongly correlated with the length of time between unclamping the aorta and coming off CPB (r = 0.94), as well as with the increase in temperature upon rewarming (r = 0.92).

Adult↗
PubMed1988

Effect of clinical pharmacy services on appropriateness of serum digoxin concentration monitoring.

The effects of four levels of clinical pharmacy services on increasing the appropriate ordering of serum digoxin concentration (SDC) determinations for cardiothoracic surgery patients were studied. During four equivalent four-month periods from 1983 to 1986, the pharmacist on the cardiothoracic surgery service provided four different levels of clinical services: no services (Period 1), participation in ward rounds only (Period 2), participation in ward rounds supplemented by the regular provision of inservice education programs (Period 3), and participation in ward rounds only (Period 4). Explicit criteria for the appropriate monitoring of digoxin therapy were developed from published criteria and an extensive literature review; all SDC determinations that did not meet one of these criteria were deemed inappropriate. All adult patients who received digoxin therapy were included in the study; data collected for each patient included the time and amount of the daily digoxin dose and the route of administration, the time at which blood was drawn for each SDC determination, and the assay results. Data were collected through a retrospective chart review for Period 1 and concurrently thereafter. The number of appropriate SDC determinations in Period 1 were compared with the total number of appropriate SDC determinations in Periods 2, 3, and 4; Periods 2 and 4 were compared with Period 3; and Period 2 was compared with Period 4. The costs avoided as the result of decreased numbers of SDC determinations ordered were calculated as the differences between the cost of inappropriate SDC determinations in Period 1 and the costs in Periods 2, 3, and 4.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac Surgical Procedures↗
PubMed1988

Developing a videocassette program for pharmacy education.

The development of a videocassette program to educate pharmacists about congestive heart failure (CHF) is described. The CHF videocassette program was developed to provide the equivalent of four hours of instruction to pharmacists in continuing-education programs or Pharm.D. degree programs. CHF was chosen as the topic because it is a common medical problem that pharmacists likely would encounter, and the material would lend itself well to visual illustration. A program-development team consisting of a pharmacist-author, an educational-design specialist, and a writer-producer was established. The group dealt first with treatment of ideas, or discussions of ways in which the educational material could best be illustrated. The pharmacist-author developed the text for the program, and the writer-producer converted the text into a script with numbered scenes. Information that could be presented more appropriately in written format was gathered into a supplemental guidebook. A storyboard script that linked the text with the audio and visual elements was developed with the help of a professional director and medical illustrator, and the program was filmed using volunteer and professional actors as well as simple animation. The program comprises two videocassettes that are 40 and 44 minutes long, respectively. The estimated cost of the production was +28,000, which includes estimates of the value of time volunteered by the pharmacist-author, educational-design specialist, nonprofessional talent, and secretaries. The program has been used for six continuing-education programs and two classes of Pharm.D. students; subjective evaluations of the program have been favorable. Videocassette technology can be applied successfully to educational programs for pharmacists.(ABSTRACT TRUNCATED AT 250 WORDS)

Costs and Cost Analysis↗
PubMed1987

Controversies in the use of transdermal nitroglycerin systems.

The role of transdermal nitroglycerin (TNTG) in the treatment of ischemic heart disease and congestive heart failure (CHF) is reviewed, with an emphasis on controversies concerning efficacy, hemodynamics, and dosing. Currently marketed rate-controlled transdermal nitroglycerin systems provide steady plasma concentrations of nitroglycerin for 24 hours. However, results of controlled trials in ischemic heart disease and CHF have raised doubts about the ability of TNTG to exert clinically important antianginal or hemodynamic benefit for the full 24-hour period. There is evidence that the duration of effect after TNTG application may persist for 24 hours, but there also is evidence of a lack of efficacy beyond 6 to 12 hours. This issue has not been resolved, but there is a trend toward use of larger doses that produce more persistent effects. The effects of conventional doses of TNTG in ischemic heart disease are modest; efficacy is based on demonstrated improvements in exercise performance. High TNTG doses (40-90 mg/24 hours) are required by many patients. In CHF, TNTG improves venous hemodynamic measurements. A dose-response relationship is not well defined. High-dose TNTG therapy is probably required to increase cardiac output and decrease systemic vascular resistance. Nitrate attenuation appears to be an important phenomenon with TNTG therapy. As with other forms of nitrate therapy, adverse effects may be a limiting factor, and clinical experience with high-dose TNTG therapy is limited. For some patients, TNTG therapy is an important addition to medical therapy. Further studies are needed to confirm reported improvements in exercise performance and hemodynamic benefits and to identify patient subsets likely to benefit from TNTG therapy.

Administration, Topical↗
PubMed1986

Current concepts in clinical therapeutics: congestive heart failure.

The epidemiology and etiology, pathophysiology, diagnosis, and treatment of congestive heart failure (CHF) are reviewed. CHF affects as many as 4 million Americans and is one of the most prevalent causes of death in hospitalized patients. Major risk factors for developing CHF include advanced age, male sex, hypertension, coronary artery disease, smoking, hypercholesterolemia, diabetes mellitus, and rheumatic heart disease. Heart failure results from decreased intrinsic myocardial contractility caused by one or more of three changes: (1) altered adrenergic nervous system function, (2) impaired delivery of calcium to contractile elements in the heart, and (3) reduced myosin-ATPase activity in the myocardium. The disease is progressive, and no intervention has yet been found to stop it effectively. CHF is diagnosed based on subjective signs and symptoms and objective assessment using auscultation, ECG, chest roentgenogram, laboratory tests, and noninvasive and invasive tests. Treatment of CHF begins with restriction of physical activity and sodium intake. Pharmacologic interventions start with either digitalis glycosides or thiazide diuretics; both may be used concomitantly as the disease progresses. Current studies are focusing on the use of angiotensin-converting enzyme inhibitors as first-line agents for CHF. When CHF worsens, loop diuretics are substituted for or added to the thiazide diuretics, and vasodilators are added to reduce the workload on the heart. Other inotropic agents, including the new bipyridine derivatives, may also be used. In patients not responding to these and other aggressive therapeutic interventions, cardiac transplantation is the only option. Despite advances in management of CHF, little improvement in overall survival has been demonstrated, and no intervention has stopped or reversed the progression of CHF.

Adrenergic beta-Agonists↗
PubMed1986

Composition of cardioplegic solutions used in nine medical centers.

Eleven institutions that participated in the Coronary Artery Surgery Study (CASS) were surveyed to obtain information about the types of cardioplegic solutions used at these institutions. A short-answer questionnaire designed to obtain specific information about the composition and method of preparation of cardioplegic solutions was sent to each institution. Institutions that did not reply within four weeks were sent a second questionnaire. Nine institutions returned completed questionnaires. Four institutions used several different cardioplegic solutions, resulting in a total of 14 evaluable solutions. Six hospitals used a chemical-based cardioplegic solution, one used a blood-based solution, and two used a combination of blood and chemicals as a cardioplegic-solution base. Chloride and potassium were found in all 14 solutions, although the amounts varied widely. Dextrose was included in eight of the nine chemical-based solutions, and bicarbonate and sodium were each used in seven of the nine solutions. Centers using chemical-based cardioplegic solutions compounded them daily or froze them with a one-week expiration date; blood-based solutions had to be prepared daily. Although interinstitutional differences in dosage were evident, the cardioplegic solutions used in the institutions participating in the CASS had many similar components. Data on the composition of these solutions can be used as a guideline for developing a cardioplegic solution.

Academic Medical Centers↗
PubMed1984

Stability of nitroglycerin in intravenous admixtures.

The stability of nitroglycerin in intravenous admixtures was studied. Admixtures containing nitroglycerin 400 micrograms/ml and each of seven injectable drugs in concentrations used clinically were prepared in triplicate in 5% dextrose and 0.9% sodium chloride injections. Admixtures were stored in glass bottles at room temperature for 24 hours in the upright position and then for 24 hours in the inverted position to ensure contact of the solution with the rubber stopper of the container. At 0, 24, and 48 hours, samples of each admixture were assayed by high-performance liquid chromatography for nitroglycerin concentration. The pH of one randomly chosen bottle of each admixture was measured at 0, 24, and 48 hours. A significant loss of nitroglycerin potency at 48 hours was observed only in admixtures containing phenytoin; in these solutions, a 9% decrease in initial nitroglycerin concentration was noted. Phenytoin crystallization was present in all phenytoin admixtures by 24 hours. Compared with initial values, no significant differences in the pH values of any admixture samples assayed at 24 and 48 hours were noted; however, admixtures containing phenytoin had the most alkaline pH values. Under the conditions studied, nitroglycerin concentrations remained above 90% of their initial values for 48 hours in all tested admixtures; however, phenytoin crystallization limits the stability of phenytoin admixtures.

Drug Combinations↗
PubMedDate not supplied

Effects of age and gender on venlafaxine and O-desmethylvenlafaxine pharmacokinetics.

This single- and multiple-dose, nonrandomized, inpatient study was conducted to determine the effects of age and gender on the pharmacokinetic profiles of the antidepressant venlafaxine and its equally active metabolite, O-desmethylvenlafaxine. The subjects were 18 elderly (age 60-80 yrs) and 18 young (age 21-44 yrs) subjects, 9 men and 9 women per age group. They received a single 50-mg venlafaxine dose followed by 50-mg doses every 8 hours for 5 days. No significant differences in venlafaxine single-dose pharmacokinetics were seen between age groups, but the steady-state half-life increased 24% in the elderly. For O-desmethylvenlafaxine, single doses had a significantly lower apparent clearance in the elderly (0.29 vs 0.38 L/hr/kg), longer half-life (13.2 vs 10.3 hrs), and 14% greater steady-state half-life. For the composite (venlafaxine+O-desmethylvenlafaxine), there was a nonsignificant 16% increase in elderly steady-state area under the curve (AUC* = AUC+activity factor AUCm), and AUC* was linear between doses and age groups. We conclude that venlafaxine dosage adjustments for age or gender are not necessary based on pharmacokinetics.

Adult↗