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Biomedical subjects

D R Rutledge

Publications and source records attributed to D R Rutledge.

28 records · Page 2Linked to original sources
PubMed1988

Dose response of inhaled gallopamil (D600), a calcium channel blocker, in attenuating airway reactivity to methacholine and exercise.

To determine if there is a dose-response relationship for calcium channel blockers in preventing experimentally induced bronchoconstriction, we evaluated the effects of inhaled gallopamil (D600), a potent methoxy derivative of verapamil, on airway reactivity to methacholine and exercise in volunteers with mild asthma. Methacholine challenges were completed by 11 subjects 2 hours before and 20 minutes after placebo, and 1, 2, 5, 10, and 20 mg of inhaled gallopamil administered in a single-blind, randomized manner on different days. Gallopamil did not significantly alter FVC, FEV1, or forced expiratory flow rate between 25% and 75% of FVC, but increased the dose of methacholine required to produce a 20% decrease in FEV1 from baseline (p less than 0.0001). The mean +/- SEM fold increase in the dose of methacholine required to produce a 20% decrease in FEV1 from baseline was 1.0 +/- 0.1 after placebo, 2.4 +/- 0.2 after 1 mg, 2.2 +/- 0.2 after 2 mg, 2.5 +/- 0.2 after 5 mg, 2.5 +/- 0.3 after 10 mg, and 2.3 +/- 0.2 after 20 mg. Thirty minutes before a standardized exercise challenge, 10 subjects inhaled 1 and 10 mg of gallopamil or placebo in a randomized, double-blind, crossover manner. The mean +/- SEM maximum decrease in FEV1 after exercise was 25.1 +/- 5% after 10 mg of gallopamil (p less than 0.01), 34.4 +/- 5% after 1 mg (p greater than 0.05), and 39.0 +/- 6% after placebo. We conclude that inhaled gallopamil only modestly alters airway reactivity to methacholine; increasing the dose greater than 1 mg did not provide greater benefit.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Determination of verapamil and its primary metabolites in serum by ion-pair adsorption high-performance liquid chromatography.

A high-performance liquid chromatographic (HPLC) method for the simultaneous quantitation of verapamil, norverapamil, N-dealkylverapamil (D617) and N-dealkylnorverapamil (D620) concentrations in serum is developed. Analysis is performed on a microparticulate (10 microns) silica column using a counter-ion solvent system (0.6 mM NaBr in methanol). Column effluent is monitored by fluorescence detection at an excitation wavelength of 203 nm. The limit of sensitivity is less than 1 ng for all compounds in serum. No potential sources of interference are identified and a coefficient of variation of less than 10% is observed on replicate verapamil determinations. The method has the advantages of complete resolution of the metabolites of verapamil, low limits of detection, high degree of reproducibility, and short analysis time.

Chromatography, High Pressure Liquid↗
PubMed1988

Effects of chronic phenobarbital on verapamil disposition in humans.

Very little is known about the effects of hepatic enzyme induction with phenobarbital on the disposition of high clearance drugs in humans. Our study was undertaken to investigate the effect of phenobarbital on both alpha-1 acid glycoprotein concentrations and total and free verapamil and its metabolites. Single oral, single i.v., and multiple oral verapamil administrations were evaluated before and after 21 days of phenobarbital treatment in healthy caucasian male volunteers. Significant changes in the pharmacokinetics of total and free verapamil and its metabolites occurred in a predictable manner. Mean total apparent oral clearance after a single dose of verapamil was increased after phenobarbital treatment (75.1 +/- 49.2 vs. 376.2 +/- 221.8 ml/min/kg, P less than .05). Clearance of free drug increased to a similar magnitude. Mean total verapamil systemic clearance was increased (9.95 +/- 1.3 vs. 18.9 +/- 8.7 ml/min/kg, P less than .05); however free drug clearance was not altered. After multiple oral administration, total verapamil apparent oral clearance was increased after phenobarbital pretreatment (21.2 +/- 9.8 vs. 91.2 +/- 28.5 ml/min/kg, P less than .05). Free drug clearance was increased similarly. Finally, the pharmacokinetic theories derived for hepatic extraction of drugs subject to a high metabolic clearance can be successfully applied to men after liver enzyme induction with phenobarbital.

Adult↗
PubMed1987

Gallopamil binding to human serum proteins.

We have determined the extent and variability in the binding of gallopamil to human serum proteins. Binding was determined by equilibrium dialysis in healthy volunteer serum, human serum albumin (45 g.l-1), and alpha-1 acid glycoprotein (AAG) (600 mg.l-1) at a pH of 7.4. Nonlinear regression analysis of gallopamil binding over a wide range of concentrations (10(-9) to 10(-4) M) in healthy volunteer serum suggested two classes of binding sites (kass.1 = 4.7 x 10(5)M-1, kass.2 = 4.1 x 10(4)M-1). These values were in close agreement with those obtained from binding to AAG and human serum albumin. Gallopamil free fraction over the concentration range of 10 to 100 ng.ml-1 was independent of concentration. The free fraction in 20 volunteers was 0.075 at a concentration of 10 ng.ml-1. Gallopamil free fractions were also determined in human serum albumin, to which various concentrations of AAG were added. Bound/free ratios correlated with AAG. As we changed the pH of the serum from 7.0 to 8.0, the free fraction changed from 0.1 to 0.05. Verapamil, lignocaine, procainamide, propranolol, 40 H-propranolol, MEGX, and NAPA all caused an increase in the free fraction of gallopamil in serum. However, tocanide, quinidine, diltiazem, GX, norverapamil, D620, D617, and desacetyl diltiazem had no effect on gallopamil binding. Therefore, the data strongly suggest AAG as the high affinity, low capacity binding site and albumin as the low affinity, high capacity binding site for gallopamil, variability in gallopamil binding can be explained by alterations in AAG concentrations, pH, and the presence of other drugs and their metabolites.

Blood Proteins↗
PubMedDate not supplied

Evaluation of intravenous amrinone: the first of a new class of positive inotropic agents with vasodilator properties.

Amrinone is the first noncatecholamine inotropic agent with substantial vasodilating properties to be approved by the Food and Drug Administration. Its use in acute congestive heart failure (CHF) is associated with significant increases in cardiac index, reductions in pulmonary capillary wedge pressure and systemic vascular resistance and little or no change in mean arterial pressure. Pharmacokinetic studies of amrinone report an elimination half-life of 2.6-8.3 hours, with slower elimination more likely in patients with compromised renal or hepatic function. Intravenous bolus doses of 0.75-3.5 mg/kg followed by infusions of 5-20 micrograms/kg/min produce hemodynamic improvements similar to those with dobutamine. Side effects with amrinone therapy are usually mild, but thrombocytopenia occurs in 2.4% of patients. Amrinone appears equally as efficacious as dobutamine in the management of acute CHF, but its role in therapy depends on efficacy and side effect data in greater numbers of patients.

Aminopyridines↗
PubMedDate not supplied

Applying managed care performance measures in community pharmacy-based outcomes research.

OBJECTIVES: (1) To introduce the National Committee on Quality Assurance's (NCQA's) Health Employer Data and Information Set (HEDIS), a set of managed care performance measures, as a tool for conducting outcomes research in the community pharmacy; (2) To demonstrate the practical application of this tool by describing three outcomes research projects conducted in an independent community pharmacy. DESIGN: Review of three outcomes research projects based on HEDIS: (1) Increasing ACEI Use in Patients with Heart Failure, (2) Cardiovascular Telepharmacy Project, and (3) Pediatric Antibiotic Callback Program. SETTING: Independent community pharmacy. RESULTS: The "Effectiveness of Care" section of HEDIS was a practical tool for designing outcomes research projects in the community setting. Improved clinical and/or service outcomes were observed in two of the projects. The challenges faced in these projects were due to the methods of implementation, rather than to the HEDIS tool itself. These projects led to a number of "lessons learned" in the conduct of outcomes research in the community pharmacy setting. CONCLUSION: Community pharmacists can use NCQA's HEDIS as a tool to help gain acceptance of and reimbursement for pharmaceutical services through the formulation of outcomes projects that are of interest to managed care organizations (MCOs) seeking accreditation status. As pharmacists report their successes to MCOs, they may be better equipped to develop reimbursement strategies for services from MCOs through their demonstration of shared goals.

Angiotensin-Converting Enzyme Inhibitors↗
PubMedDate not supplied

Are there beta-adrenergic receptor response differences between racial groups?

Beta-adrenergic receptor (BAR) agonists and antagonists are among the most widely used drugs in America today. This review highlights the importance of cross-racial studies in evaluating BAR effects because heterogeneity in pharmacologic response among humans exists. Clinicians and basic scientists in the drug development industry need to acknowledge racial differences in antihypertensive drug responses and prevent various racial groups from being underrepresented in clinical trials. This article reviews the influence of race on BAR responses with emphasis on blacks and whites. Information from patients with hypertension, healthy volunteers, and in vitro studies is presented.

Adrenergic beta-Antagonists↗
PubMedDate not supplied

Possible correlation between glycemia and blood pressure in black, diabetic, hypertensive patients.

OBJECTIVE: To determine if there is any association between glycemia and blood pressure in black patients with hypertension and diabetes mellitus whose antihypertensive medications had been unchanged for six months. DESIGN: Retrospective, from March 1990 through February 1991. SETTING: Internal medicine ambulatory clinic at Detroit Receiving Hospital/University Health Center. PATIENTS: Patients seen during this period with hypertension and type II diabetes. Of the 639 possible subjects, 124 met the following criteria: (1) no change in antihypertensive medications for six months, (2) absence of secondary hypertension, and (3) weight change (if any) was less than five percent. Changes in antihypertensive medication(s) excluded 388 patients, secondary hypertension excluded 3, weight changes of more than five percent excluded 94, and lack of matching postprandial capillary blood glucose (PCBG) values excluded 30. The mean age of the subjects was 66.8 years, mean diabetes duration was 12.0 years, mean PCBG was 10.7 mmol, mean systolic blood pressure (SBP) was 1543 mm Hg, mean diastolic blood pressure (DBP) was 90.1 mm Hg. There were 28 men in the study and 96 women; 90 were obese (body mass index greater than 25 kg/m2) and 34 were nonobese. The diabetes was managed with insulin in 67 patients, with sulfonylureas in 50, and with diet in 7. INTERVENTION: None MAIN OUTCOME MEASURES: SBP and DBP versus PCBG at matching time both at baseline and at six months. RESULTS: There was a positive association between blood pressure measurements and glycemia. Overall change in SBP was strongly correlated with PCBG changes (r = 0.745, p less than 0.0001). Improved glycemia correlated with improved SBP control (r = 0.330, p less than 0.0024). Deterioration of glycemia correlated with a worsening of SBP control (r = 0.445, p less than 0.0053). The method of blood glucose control had no statistically significant effect (ANOVA) on these results. CONCLUSIONS: Glycemia is positively associated with blood pressure.

Aged↗