Pharmacy and Pharmaceutical Sciences Commons^™

Effect Of Ceftazidime On Systemic Cytokine Concentrations In Rats, Khalid M. Alkharfy, John A. Kellum, Reginald F. Frye, Gary R. Matzke

Pharmacotherapy and Outcomes Science Publications

The effect of a single dose of ceftazidime on circulating concentrations of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) in a rat model of sepsis was studied. IL-6 concentrations were significantly elevated (100 to 200 times the baseline) 6 h after ceftazidime administration in both septic and nonseptic (control) rats. TNF-α concentrations increased significantly in nonseptic (∼40 times the baseline) rats but not septic (∼2 to 3 times the baseline) rats. Ceftazidime administration was not associated with an increase in endotoxin concentrations. These findings suggest that ceftazidime modulation of proinflammatory cytokine concentrations may be independent of its antimicrobial properties.

Determinants Of Ceftazidime Clearance By Continuous Venovenous Hemofiltration And Continuous Venovenous Hemodialysis, Gary R. Matzke, Reginald F. Frye, Melanie S. Joy, Paul M. Palevsky

Pharmacotherapy and Outcomes Science Publications

Although several dosage adjustment regimens have been proposed, there is little quantitative information to guide the initiation of ceftazidime therapy in patients who are receiving continuous renal replacement therapy. To determine the clearance of ceftazidime by continuous venovenous hemofiltration (CVVH) and continuous venovenous hemodialysis (CVVHD), we performed controlled clearance studies with stable hemodialysis patients with three hemofilters: a 0.6-m2 acrylonitrile copolymer (AN69; Hospal) filter, a 2.1-m2 polymethylmethacrylate filter (PMMA; Toray) filter and a 0.65-m2 polysulfone (PS; Fresenius) filter. Subjects received 1,000 mg of ceftazidime intravenously prior to the start of a clearance study. The concentration of ceftazidime in multiple plasma …

Kinetics And Mechanisms Of Macromolecular Disposition In The Rat Lung, Masahiro Sakagami

Theses and Dissertations

The kinetics and mechanisms of macromclecular absorption from the airways of the rat lung were studied in vivo and in vitro, following identical solute administration methods. The isolated perfused rat lung (IPRL) was used as an in vitro model, and the disposition of 7.4 and 4.3 kDa fluorophore-labeled polyhydroxyethylaspartamide (F-PHEA) and other small and macromolecular reference solutes was investigated across doses and in the presence of a variety of biochemical inhibitors.

Absorption profiles of F-PHEA, and the solute's lung distribution at different times after administration, were statistically identical in vivo and in vitro, showing that the IPRL possessed a viable …

Adenosine 3', 5'-Cyclic Monophosphate Activation Of Islet Chloride Channels, Anjali Varandani

Theses and Dissertations

The objective of this thesis was to understand the regulation of islet Cl⁻ current by cAMP. This current, known as I_cl,islet flew is the first Cl⁻ channel current characterized in pancreatic �� cells. I_cl,islet has been hypothesized to modulate insulin secretion through changes in islet electrical activity. Both 5 ��M forskolin and 100 ��M IBMX (3-isobutyl-1-methylxanthine), agents that increase intracellular cAMP, were shown to activate an outwardly-rectifying ionic current in HIT cells that closely resembled I_cl,islet. The current was blocked when iodide was substituted for external Cl⁻ or when the Cl⁻ channel blocker niflumic acid was …

Pharmacokinetics Of Vancomycin In Critically Ill Infants Undergoing Extracorporeal Membrane Oxygenation, R. Davis Maker, Joseph T. Dipiro, Jatinder Bhatia

Publications from the Office of the Dean

Extracorporeal membrane oxygenation (ECMO) is a widely used therapy for neonates with respiratory failure. Because of sepsis, many of these infants require antibiotics like vancomycin during ECMO treatment. ECMO transiently alters renal function and increases the circulating blood volume by 75%. Initial vancomycin pharmacokinetics were determined in 12 infants undergoing ECMO to determine an adequate drug administration regimen. Vancomycin dosage was based on current recommendations for weight and gestational age. Pharmacokinetic parameters were determined by fitting the data to a two compartment model. This study yielded a mean steady-state volume of distribution of 1.1 +/- 0.5 (range, 0.6 to 2.1) …

Physical And Chemical Stability Of Spray Dried Sugars And Protein-Sugar Molecuiar Mixtures For Inhalation, Venkatesh Naini

Theses and Dissertations

The feasibility of producing inhalable microparticles of sugars and protein-sugar molecular mixtures using spray drying was investigated as an alternative to conventional micronization techniques. Four sugars; lactose (L), trehalose (T), sucrose (S) and mannitol (M) were spray dried using a commercial bench-top spray dryer and their physicochemical stability, with respect to particle size, moisture uptake and crystallinity changes, investigated after storage at 23%, 52%, 75% and 93% relative humidity (RH) and 25 °C for 30 days. Two crystalline size fractions (“coarse” = 125-212 μm and “fine” = 44-74 μm) of each sugar, were also characterized, as possible replacements for lactose …

Pharmacokinetics And Pharmacodynamics Of Ethanol In Healthy Volunteers: Effects Of Input-Rate And Degree Of Ethanol Exposure On Subjective And Objective Measures Of Impairment, Vijay A. Ramchandani

Theses and Dissertations

The goal of this project was to investigate the effect of input-rate (oral and intravenous) and degree of exposure on the pharmacokinetics of ethanol and on subjective and objective measures of impairment, as well as on the development of acute tolerance to the effects of ethanol in young, healthy volunteers.

The primary objective of this research was to test the following hypotheses: 1) the rate and degree of ethanol exposure (oral and intravenous) in normal healthy males and females affect the pharrnacokinetics (PK) and pharmacodynarnics (PD) of ethanol in a non-linear fashion; 2) the EEG changes after ethanol administration correlate …

Evaluation Of Cannabinoid Receptor Interaction Of Anandamide, The Endogenous Cannabinoid Receptor Ligand, Irma Bateman Adams

Theses and Dissertations

Recent evidence implicates anandamide as the endogenous ligand for the cannabinoid receptor. One purpose of this study was to determine the structural requirements for anandamide's receptor interaction and the influence of phenylmethylsulfonyl fluoride (PMSF), an enzyme inhibitor, on receptor affinity. A second objective was evaluation of the correlation between affinities of the analogs and in vivo pharmacological activities. The ability of anandamide and analogs to displace [3H]- CP 55,940 was determined by a filtration assay. Displacement curves for anandamide in the presence of PMSF produced a Ki of 89 ± 10 nM; without PMSF the Ki increased to 5400 ± …

Lipopolysaccharide-Reactive Immunoglobulin E Is Associated With Lower Mortality And Organ Failure In Traumatically Injured Patients, Joseph T. Dipiro, Robert G. Hamilton, Thomas R. Howdieshell, N. Franklin Adkinson Jr., Arlie R. Mansberger Jr.

Publications from the Office of the Dean

Antilipopolysaccharide (anti-LPS) immunoglobulin G (IgG) and IgM have been associated with protection from LPS effects in vivo. We investigated the presence of IgE and anti-LPS in 32 patients that had experienced severe traumatic injury and in 35 healthy volunteers; we also investigated whether IgE anti-LPS was associated with important clinical events. Plasma samples were collected daily from patients in the intensive care unit and on one occasion from volunteers; the samples were assayed for IgE anti-LPS. IgE anti-LPS was assayed by enzyme-linked immunosorbent assay with monoclonal anti-human IgE as the capture antibody. Detection was accomplished with biotin-labeled LPS (Escherichia coli …

Facilitation Of Penicillin Haptenation To Serum Proteins., Joseph T. Dipiro, N. Franklin Adkinson Jr., Robert G. Hamilton

Publications from the Office of the Dean

Traditionally, penicillin binding to serum proteins was believed to be a passive chemical process; however, it appears to be facilitated by serum factors. The objectives of this in vitro investigation were to examine facilitated penicillin haptenation, to study the kinetics of haptenation, and to determine the nature of haptenation-facilitating factors. The model involved addition of [3H]benzylpenicillin to serum or albumin solutions (at pH 7.3 to 7.4) and incubation at 37 degrees C for up to 72 h. The extent of penicillin binding to proteins in serum was found to be four- to fivefold higher than with solutions having comparable concentrations …

In Vitro Protein Binding Of Cefonicid And Cefuroxime In Adult And Neonatal Sera., John M. Benson, F. Douglas Boudinot, Andrew T. Pennell, Francesca E. Cunningham, Joseph T. Dipiro

Publications from the Office of the Dean

The levels of in vitro protein binding of cefonicid and cefuroxime in human adult and neonatal sera were compared.Binding parameters for each drug were determined within the concentration range of 25 to 3,000 micrograms/ml.Cefonicid exhibited concentration-dependent protein binding in both types of sera, with more extensive binding in adultserum at all concentrations. Two classes of binding sites were found: a high-affinity, saturable site and a low-affinity, nonspecific site. Cefuroxime also showed two-class, concentration-dependent protein binding in adult serum, but bindingin neonatal serum was to a single class and was independent of drug concentration. Parameters for class 1 binding sites for …

Safety And Pharmacokinetics Of Multiple Doses Of Intravenous Ofloxacin In Healthy Volunteers, David R. P. Guay, John A. Opsahl, F. Gilbert Mcmahon, Ramon Vargas, Gary R. Matzke, Soledad Flor

Pharmacotherapy and Outcomes Science Publications

The safety and pharmacokinetics of ofloxacin in 48 healthy male volunteers were studied in a two-center, randomized, double-blind, placebo-controlled study. Ofloxacin (200 or 400 mg) or placebo was administered as 1-h infusions every 12 h for 7 days. Plasma ofloxacin concentrations were measured by high-performance liquid chromatography. Mean harmonic half-lives ranged from 4.28 to 4.98 h in the 200-mg dosing group and from 5.06 to 6.67 h in the 400-mg dosing group. Intragroup comparisons of trough plasma concentration-versus-time data from study days 2 through 7 revealed that steady state was achieved by day 2 of both multiple-dose regimens. Intergroup comparisons …

Evaluation Of Quantitative Electroencephalography For Assessment Of Central Nervous System Stimulant Response, Patricia W. Slattum

Theses and Dissertations

The objective of this investigation was to evaluate quantitative electroencephalography (EEG) as a measure of CNS stimulation. The reproducibility and sensitivity of quantitative EEG was compared to neuroendocrine, mood, and psychomotor performance measures.

The study was conducted in two parts. The first part investigated the inter- and intra-individual variability associated with a series of pharmacological response measures under baseline (no drug) conditions. It was an open-label pilot study in which eight healthy male volunteers underwent a series of tests (EEG, visual continuous performance task (CPT), a finger tapping task, and self-rated mood scales) repeated eight times over a 12 hour …

Pharmacokinetics Of Ceftibuten-Cis And Its Trans Metabolite In Healthy Volunteers And In Patients With Chronic Renal Insufficiency, Judy Shepard Kelloway, Walid M. Awni, Chin C. Lin, Josephine Lim, Melton B. Affrime, William F. Keane, Gary R. Matzke, Charles E. Halstenson

Pharmacotherapy and Outcomes Science Publications

The impact of renal insufficiency on the dispositions of 300 mg of orally administered ceftibuten-cis, a new broad-spectrum oral cephalosporin, and its primary metabolite ceftibuten-trans was characterized in 30 adult subjects. Subjects were divided into five groups of six subjects each on the basis of their 24-h ambulatory creatinine clearances (CL_CR). The apparent total body clearance (CL_P/F; where F is absolute bioavailability) and renal clearance of ceftibuten-cis were significantly lower in subjects with end-stage renal disease (on maintenance hemodialysis; group V) and in those with severe (CL_CR, 5 …

Pharmacokinetics Of Cefepime In Patients With Respiratory Tract Infections, J. M. Kovarik, J. C. Ter Maaten, C. M. A. Rademaker, M. Deenstra, I. M. Hoepelman, H. C. Hart, Gary R. Matzke, J. Verhoef

Pharmacotherapy and Outcomes Science Publications

The steady-state pharmacokinetics of cefepime were evaluated in 10 middle-aged and elderly patients with acute lower respiratory tract infections who were receiving 1 g intravenously every 12 h. One preinfusion and 15 postinfusion serum samples and total urine output were collected over one dosing interval between days 3 and 8 of therapy. Cefepime concentrations in serum over time exhibited a multicompartmental profile. Peak and trough concentrations in serum determined by a validated high-performance liquid chromatography method were 71.2 +/- 17.2 (mean +/- standard deviation) and 6.0 +/- 4.9 mg/liter, respectively. The steady-state volume of distribution was 0.22 +/- 0.05 liter/kg. …

Apparent Biliary Pseudolithiasis During Ceftriaxone Therapy, Karen L. Heim-Duthoy, Erskine M. Caperton, Robert Pollock, Gary R. Matzke, Dirk Enthoven, Phillip K. Peterson

Pharmacotherapy and Outcomes Science Publications

Biliary pseudolithiasis has been reported in patients who received ceftriaxone therapy. To examine this phenomenon further, serial gallbladder sonograms were evaluated in 44 adult patients who received intravenous ceftriaxone at 2 g or a placebo daily for 14 days in a double-blind controlled study. Ultrasound examinations of gallbladders were performed on days 1 and 14 of therapy and 2 weeks posttherapy if abnormalities were observed on day 14. Eight patients were unevaluable because of abnormal base-line gallbladder sonograms. Thirty-six patients (ceftriaxone, n = 28; placebo, n = 8) demonstrated normal baseline gallbladder sonograms and were evaluated for the development of …

Assessment Of Cefazolin And Cefuroxime Tissue Penetration By Using A Continuous Intravenous Infusion., John E. Connors, Joseph T. Dipiro, Ronald G. Hayter, K. Dale Hooker, Johnny A. Stanfield, Timothy R. Young

Publications from the Office of the Dean

A continuous intravenous infusion was used to assess the tissue penetration of cefazolin (14 subjects) and cefuroxime (15 subjects) in orthopedic surgery patients. Subjects were randomly assigned to receive a continuous intravenous infusion of cefazolin (mean, 178.6 mg/h) orcefuroxime (mean, 330.0 mg/h) at a rate estimated to achieve a target steady-state total concentration of 50 micrograms/ml in serum. The infusion was initiated 12 to 14 h before surgery, and blood and muscle tissue samples were collected intraoperatively at the times of incision and wound closure. Although there was a significant difference between the free concentrations ofcefazolin (at incision, 9.3 micrograms/ml; …

Effects Of Magnesium-Aluminum Hydroxide And Calcium Carbonate Antacids On Bioavailability Of Ofloxacin, Soledad Flor, David R. P. Guay, John A. Opsahl, Kenneth Tack, Gary R. Matzke

Pharmacotherapy and Outcomes Science Publications

The effects of 15- and 5-ml doses of magnesium-aluminum hydroxide (MAH) and calcium carbonate (CC) antacids, respectively, on the bioavailability of ofloxacin after single oral 400-mg doses of ofloxacin were investigated in a 32-subject, randomized, crossover, open-label study. On four separate occasions, subjects received ofloxacin alone or antacid 24 h before, 2 h before, or 2 h after ofloxacin administration (n = 16 for each antacid). CC administration had no significant effect on the rate and extent of ofloxacin absorption regardless of the timing of antacid administration. A small but significant negative effect of MAH administration 2 h before ofloxacin …

Pharmacokinetics Of Gentamicin In Neonates On Extracorporeal Membrane Oxygenation., W. Michael Southgate, Joseph T. Dipiro, Alex F. Robertson

Publications from the Office of the Dean

Extracorporeal membrane oxygenation (ECMO) has been used in more than 1,000 infants in 50 centers in the United States. The extracorporeal circuit contains approximately 400 ml of blood, an amount exceeding the blood volume of most full-term neonates. The effect of this additional blood volume on drug disposition is unknown. In this study, we determined the pharmacokinetic parameters of gentamicin in 10 infants on ECMO. Gentamicin concentrations were determined by a fluorescence polarization immunoassay. Pharmacokinetic parameters were determined from these concentrations by using a two-compartment model. Our study demonstrated a mean steady-state volume of distribution of 0.51 +/- 0.11 liters/kg, …

Effect Of Hemorrhagic Shock On Cefazolin And Gentamicin Pharmacokinetics In Dogs., Paul L. Dickson, Joseph T. Dipiro, Katherine A. Michael, Richard P. F. Cheung, Edward M. Hall

Publications from the Office of the Dean

The physiologic response to traumatic injury may alter the disposition of drugs and thereby affect their therapeutic or toxic potential. A study was conducted in 10 mongrel dogs to determine theeffect of experimental hemorrhagic shock with resuscitation on the pharmacokinetics of gentamicinand cefazolin. Single simultaneous intravenous doses of gentamicin (3 mg/kg) and cefazolin (25 mg/kg) were administered to each animal on an initial study day, after which serial blood and urine collections were performed. After 1 week, a standard hemorrhagic shock model was applied to each animal. Shock was continued for 1 h, after which the animal was resuscitated with …

Development Of The Analytical Methodology For Pyrimethamine And Its Application To Studies Of Partitioning And Binding In The Subcompartments Of Blood, Anita C. Rudy

Theses and Dissertations

An original HPLC assay was developed for pyrimethamine (PYR) in plasma, RBCs, and buffer for the purpose of studying its plasma protein binding and RBC partitioning.

Equilibrium dialysis (ED) was used to study protein binding. Isotonic phosphate buffer used in ED did not prevent small volume shifts. The pH of the plasma affected the protein binding of PYR although it was not significant for the comparison of binding at pH 7.4 vs. 8.0. PYR at 1000 ng/ml averaged 93.1% bound to plasma proteins. Binding to pure human albumin was 86.5% at lower levels of albumin and PYR (350 ng/ml). There …

Alternative Pharmacokinetic Models In End Stage Renal Disease During Continuous Ambulatory Peritoneal Dialysis, Eugenio Cefali

Theses and Dissertations

An important principle of pharmacokinetic modeling is to use the least complicated model possible that adequately describes the process studied. Pharmacokinetic studies in peritoneal dialysis often attempt to describe the time course of drug concentration in the dialysate. Peritoneal dialysis patients are subjected to the inconvenience and risk of infection associated with sampling peritoneal fluid. Alternative pharmacokinetic models were used to study drug distribution during continuous ambulatory peritoneal dialysis (CAPD). Efficient pharmacokinetic models of distribution in the peritoneal cavity were described for three drugs and the classes they represent.

Procainamide pnarmacokinetics were determined in six CAPD patients. The time course …

Intraoperative Ceforanide Pharmacokinetics And Protein Binding., Joseph T. Dipiro, Samir M. Bayoumi, Joseph J. Vallner, Robert R. Nesbit, Rajeev Gokhale, J. Peter Rissing

Publications from the Office of the Dean

The pharmacokinetics and protein binding of ceforanide were studied in 15 patients undergoing cholecystectomies. Each patient received ceforanide (20 mg/kg) intravenously on arrival in the operating room, after which serial blood samples were collected during the elimination phase for determination of total and free ceforanide concentrations in the serum. A high-pressure liquid chromatography assay was used, with a centrifugal filtration system for free-drug determinations. Serum concentration data for each individual were subjected to linear regression to determine the elimination rate constants (total and free drug), volumes of distribution, and systemic clearances. The mean elimination rate constants were 0.41 and 0.50 …

Evaluation Of Analytical, Pharmacokinetic And Pharmacodynamic Methods For The Study Of Digoxin, Santosh John Vetticaden

Theses and Dissertations

The primary objective of the research was to investigate the pharmacodynamics of digoxin in dogs. Initially an assay specific for digoxin in the presence of its major metabolites, viz., digoxigenin, digoxigenin mono-digitoxoside, digoxigenin bis-digitoxoside and dihydrodigoxin was developed using HPLC-RIA. Methodology for non-invasive measurement of left ventricular ejection time (LVET) and other systolic time intervals (STI) in beagle dogs were developed. This involved surgery for exteriorization of the carotid artery in the dogs and subsequent measurements of LVET and STI after recovery. STI, heart rate (HR) and digoxin levels were monitored in normal beagle dogs administered 0.05 mg/kg or 0.025 …

Lack Of Influence Of Commonly Used Drugs On Bioassay Indicator Organisms., Joseph T. Dipiro, A. Thomas Taylor, John C. H. Steele Jr.

Publications from the Office of the Dean

Many commonly used pharmaceutical agents have been found to inhibit bacterial growth in vitro. Determinations of antimicrobial concentrations in sera of patients taking nonrecognized antibacterial agents could possibly be altered if bioassay systems are utilized for the determinations. We therefore attempted to determine the in vitro effect of commonly used drugs on bioassay indicator organisms. Fifty-one different agents (antihistamines, anticholinergics, central nervous system agents, cardiovascular agents, analgesics, steroids, muscle blockers, and other miscellaneous agents) were tested for inhibition or enhancement of the growth of Bacillus subtilis, Staphylococcus aureus, Micrococcus luteus, and Klebsiella pneumoniae. None of the agents tested exhibited any …

Synthesis Of Mesoionic Nucleosides As Potential Antineoplastic Agents, Shanaz Mohammedali Tejani

Theses and Dissertations

During the past few decades, analogs of purine nucleosides have been described that are modified either in the heterocyclic base, sugar moiety or both, and many of these modified nucleosides display antiviral and/or antineoplastic activity. The Class II mesoionic purinones are isosteric with their non~mesoionic purinone counterparts. It is conceivable that the mesoionic purinone nucleosides might constitute an entirely novel class of modified nucleosides with potential chemotherapeutic activity. That the mesoionic heterobases are bioisosteric as well as isosteric with non-mesoionic purinones was realized by demonstrating that certain mesoionic xanthine derivatives, such as Anhydro-8-ethylw-5-hydroxy-7-oxo-l,3,4-thiadiazolo[3,2-a]pyrimidinium hydroxide and Anhydro-6-p-chlorobenzyl-8-ethyl-5-hydroxy-7-oxo—l,3,4—thiadiazolo [3,2-a]pyrimidinium hydroxide were comparable …

Synthesis Of 3-(Substituted-Aryl)-1,2,3,4-Oxatriazolium-5-Olates As Potential Hypotensive Agents, Mary Quinn Lund

Theses and Dissertations

Hypertension or high blood pressure is a major cause of illness and death in the United States today.^1,2 An estimated thirty-six million people suffer from this disease.³ Prolonged hypertension and its attendant strain on various organs may cause heart failure, brain stroke or kidney damage.⁴ Usually, a pressure of 140/90 mm Hg is taken to be the dividing line between normotension and hypertension.^5,6

The hypertensive condition is generally characterized as either primary (essential) hypertension or secondary hypertension.¹ A specific cause can be identified in secondary hypertensive patients, such as, pheochromocytoma or adrenal tumor. These causes …

Synthesis And Biological Evaluation Of Sparsomycin Analogues, Scherer Preston Sanders

Theses and Dissertations

In 1962, Owen, Dietz, and Camiener reported the isolation of a new antitumor antibiotic from the culture filtrate of Streptomyces sparsogenes. The structure of the crystalline antibiotic, named sparsomycin, remained elusive until 1970, when Wiley and MacKellar reported results of spectroscopic and degradation studies which elucidated the structure. In addition to the molecular structure, investigators have examined the mechanism of action, toxicity, and related analogues, striving to establish sparsomycin or a synthetic analogue's usefulness as an effective chemotherapeutic agent.

The initial pharmacological evaluation of sparsomycin revealed it possessed activity against KB human epidermoid carcinoma cells, a variety of gram-negative and …

[Beta]-(2-Hydroxyphenyl)Ethanolamine Hydrochloride [2-Amino-1-(2-Hydroxyphenyl)Ethanol Hydrochloride], Alexandros Makriyannis, James B. Anderson, Joseph T. Dipiro, Edward Kostiner, Gilbert Hite

Publications from the Office of the Dean

CsH~2NO2+.C1 -, m.p. 441-449 K (from ethyl acetate), P212~2 l, a = 7.363 (2), b = 21.824 (6), c = 5.790 (2)/~, Z = 4, D x = 1.354, D m = 1.356 Mg m -3 (flotation: CC14-C6H6). The structure was solved by MULTAN. Full-matrix least-squares refinement converged to R = 0.057 for the R configuration and to R = 0.056 for the S configuration (P < 0.05). This is consistent with spontaneous resolution of the title compound, single crystals of which provided optically active aqueous solutions. A partially occupied oxygen site O(1)' is attributed to the oxidation of the alkyl hydroxyl group to a ketone during the data collection. The CI- is hydrogen bonded to H2(N)554, H3(N)555, and 1-t(O2)655 (2.37, 2-19, and 2.10 A). Both O(1) and 0(2) are internally hydrogen bonded [HI(N)...O(1), 2.41 and H(O1)...O(2) = 2.24 A]. Intramolecular hydrogen bonding may account for the unusual pharmacological properties of this compound in which only the N-C(1)-C(2)-O(1) and the O(1)-C(2)- C(3)-C(4) and O(1)-C(2)-C(3)-C(8) torsion angles (-41, -60, +122 ° ) differ significantly from those of other phenylethanolamines.

Interactions Of Ethanol And Methadone, Vijay Aggarwal

Theses and Dissertations

The effects of ethanol administration on the antinociceptive activity, lethal properties and brain concentration of methadone, were investigated. The effect of ethanol on the antinociceptive activity of methadone was assessed by the hot-plate and tail-flick tests. Concentrations of methadone in the brain were determined by the use of 3H-methadone as well as by gas liquid chromatographic analysis. The study showed that moderate doses of ethanol did not alter tail-flick or hot-plate response by themselves. However, when combined with methadone, ethanol produced a significant increase in the antinociceptive effectiveness of methadone as measured by both a decrease in the ED50 of …