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Biomedical subjects

D S North

Publications and source records attributed to D S North.

At least 19 recordsLinked to original sources
PubMed2001

Gatifloxacin, an advanced 8-methoxy fluoroquinolone.

Gatifloxacin is a new 8-methoxy-fluoroquinolone antibiotic approved for use in the United States in December 1999. It has a broad spectrum of activity with potent activity against gram-positive bacteria, including penicillin-resistant Streptococcus pneumoniae, as well as excellent activity against gram-negative and atypical organisms. Gatifloxacin is available in both oral and injectable forms and is administered once/day. Bioavailability is 96%, with a plasma half-life of approximately 8 hours in individuals with normal renal function. Elimination is primarily renal excretion of unchanged drug with no cytochrome P450-mediated metabolism. The drug is distributed extensively into tissues and fluids and has a favorable pharmacodynamic profile against important pathogens. It had excellent efficacy in clinical studies of acute sinusitis, acute bacterial exacerbations of chronic bronchitis, community-acquired pneumonia, complicated and uncomplicated urinary tract infections and pyelonephritis, skin and skin structure infections, and uncomplicated gonococcal infections. The agent is well tolerated, with no evidence of hepatic, cardiac, or phototoxicity noted thus far. Drug interactions are uncommon; however, like other fluoroquinolones, coadministration with multivalent cations should be avoided due to significantly decreased absorption. Gatifloxacin should prove to be a safe and effective agent for a wide variety of infections.

Animals↗
PubMed1997

A cost-effective approach to the use of selective serotonin reuptake inhibitors in a Veterans Affairs Medical Center.

In light of the tremendous expansion in the number of selective serotonin reuptake inhibitors available to the clinician, the Pharmacy and Therapeutics Committee of the Denver Veterans Affairs Medical Center considered the advantages and disadvantages of fluoxethine, paroxetine, and sertraline, to determine which agent or agents would be carried on the formulary. The committed recommended sertraline as the preferred agent for the treatment of depression, panic disorders, and obsessive-compulsive disorders. The purpose of this retrospective study was to assess the economic outcome of that decision. The study population consisted of patients at the medical center who were receiving selective serotonin reuptake inhibitors during January through March of 1994 and those were receiving these agents between September 1995 and January 1996. The expanded collection period in 1995-96 was due to a relatively new medical center policy to offer 90-day fills on medication to reduce costs. The extended collection period assured a 100% sample of patients receiving these agents. The 1994 fluoxetine to sertraline dosage equivalency ratio was 20 mg:55.6 mg, based on average daily doses of fluoxetine and sertraline of 32.7 and 90.9 mg, respectively. The cost to the medical center for an average daily dose of fluoxetine was $1.86; sertraline cost $1.22 per day. The 1996 fluoxetine to sertraline dosage equivalency ratio (20 mg:51.3 mg) had not changed significantly since 1994, indicating that the dose of 20 mg of fluoxetine remained very close to a 50-mg dose of sertraline. The average daily doses of fluoxetine and sertraline (34.9 mg and 89.7 mg, respectively) were not significantly different than the 1994 doses. Only 33 patients had been prescribed paroxetine (average daily dose, 32.4 mg). On the basis of these values, the average daily cost of fluoxetine to the medical center was $2.01, compared with $1.18 for sertraline and $1.24 for paroxetine. This $0.83 per patient per day drug acquisition cost difference between fluoxetine and sertraline results in a drug cost reduction of $302,674 per year.

Antidepressive Agents, Second-Generation↗
PubMed1995

Pharmacoeconomic benefit of antibiotic step-down therapy: converting patients from intravenous ceftriaxone to oral cefpodoxime proxetil.

OBJECTIVE: To evaluate the economic benefit associated with the early conversion of therapy from intravenous ceftiaxone to the comparable oral third-generation cephalosporin, cefpodoxime proxetil. DESIGN: Open-label, unblind, nonrandomized clinical trial. SETTING: A 360-bed Veterans Affairs Medical Center. PATIENTS: Forty patients who began receiving intravenous ceftriaxone for either a community-acquired pneumonia or a complicated urinary tract infection. INTERVENTION: twenty patients were selected, based on clinical assessment, to be converted from intravenous ceftriaxone to oral cefpodoxime proxetil. Twenty other comparable patients who would have been appropriate for step-down therapy, did not receive pharmacy intervention and were used as a control group. MEASUREMENTS: Both groups were assessed and compared for length of ceftiaxone therapy, length of oral follow-up therapy (if any), length of hospitalization, results of culture and sensitivity testing, treatment success and readmissions, and cost of respective therapeutic regimens. RESULTS: In the cefpodoxime study group, the average time receiving intravenous and oral antibiotics was 9.1 days at a total cost of $3040.26 for the 20 patients. In the control group, the average time receiving intravenous and oral antibiotics was 11.9 days at a total cost of $3961.26. A savings of $46.05 per patient was achieved. Patients receiving step-down therapy averaged 1 fewer day of hospitalization. CONCLUSION: Pharmacist intervention and cefpodoxime step-down therapy were associated with decreased overall antibiotic costs in our intravenous-to-oral program.

Administration, Oral↗
PubMed1992

Acute renal failure in an elderly woman following intramuscular ketorolac administration.

OBJECTIVE: To report a case of ketorolac tromethamine-induced acute renal failure and to discuss the risk factors that make patients more susceptible to the renal effects of nonsteroidal antiinflammatory drugs (NSAIDs). DATA SOURCES: Case reports and review articles identified by MEDLINE. Indexing terms included ketorolac, renal failure, and NSAIDs. DATA EXTRACTION: Data were abstracted from pertinent published English-language sources and were reviewed by all authors. DATA SYNTHESIS: Ketorolac is an intramuscularly administered NSAID with many of the same adverse effects associated with other oral NSAIDs. Although reversible depression of renal function has been associated with several NSAIDs, to date there have been no published reports of acute renal failure secondary to ketorolac administration. A 71-year-old woman received three doses of ketorolac to control the pain associated with pelvic and T11-T12 compression fractures. Over the next two days, the patient developed signs and symptoms of acute renal failure, including significant increases in blood urea nitrogen, serum creatinine, and peripheral edema. These signs and symptoms resolved over the next three to four days. Certain risk factors, several of which were present in this woman, make individual patients more susceptible to the renal affects of NSAIDs. These risk factors include advanced age, cirrhosis, volume depletion, congestive heart failure, gastrointestinal bleeding, and preexisting mild renal dysfunction. CONCLUSIONS: Caution should be taken when initiating ketorolac or any NSAID therapy with specific attention to risk factors that predispose a patient to renal dysfunction.

Aged↗
PubMed1990

Anistreplase: a novel thrombolytic agent for acute myocardial infarction.

Anistreplase, a modified congener of streptokinase, is a recently approved thrombolytic agent used in the treatment of acute myocardial infarction (AMI). Clinical studies have demonstrated anistreplase to be equally efficacious as intracoronary streptokinase when given within four hours of the onset of chest pain. Thirty units, given as a single bolus intravenous injection, result in reperfusion rates of approximately 60-70 percent. The adverse-effect profile of anistreplase compares favorably with that of streptokinase, with hemorrhagic complications being the most serious. Anistreplase has two distinct advantages over both streptokinase and alteplase: (1) it can be administered as a single bolus intravenous injection and (2) it has a longer half-life which may result in decreased reocclusion rates. Anistreplase therapy is associated with reductions in both short- and long-term mortality and has been shown to preserve left ventricular function. A large, long-term, comparative clinical trial (Third International Study of Infarct Survival or ISIS-III) investigating morbidity and mortality rates with streptokinase, alteplase, and anistreplase is ongoing, as is a direct comparative study against alteplase alone (TEAM-3, Multicenter Thrombolytic Trials of Eminase in Acute Myocardial Infarction).

Anistreplase↗
PubMed1988

The effect of histamine-2 receptor antagonists on tocainide pharmacokinetics.

The effects of cimetidine and ranitidine on tocainide pharmacokinetics were assessed in seven healthy subjects, using a randomized, double-blind, placebo-controlled, cross-over study design. After a 400-mg oral dose of tocainide, the area under the concentration-time curve decreased from (mean +/- SD) 31.64 +/- 14.16 micrograms.hr/mL during placebo, to 23.10 +/- 7.33 micrograms.hr/mL during cimetidine (P less than .05). Similarly, the peak tocainide concentrations were 2.81 +/- 0.89 micrograms/mL and 1.70 +/- 0.44 micrograms/mL with placebo and cimetidine, respectively (P less than .05). There was no change in the above parameters between ranitidine and placebo. The terminal half-life and renal clearance of tocainide were not altered by either H2-receptor antagonists, compared with placebo. However, the total amount of tocainide excreted unchanged in the urine, decreased from 159.8 +/- 14.7 mg with placebo to 136.8 +/- 26.8 mg with cimetidine (P less than .05), whereas there was no change with ranitidine. These data indicate that cimetidine, but not ranitidine, causes a decrease in the bioavailability of tocainide and that neither agent alters the apparent elimination rate of tocainide.

Adult↗
PubMed1986

The influence of diltiazem hydrochloride on trough serum digoxin concentrations.

A significant drug interaction between verapamil and digoxin, resulting in elevated serum digoxin concentrations, has been well documented in the medical literature. However, a similar interaction between digoxin and the calcium channel blockers nifedipine and diltiazem has not been conclusively established. This study investigated the influence of diltiazem hydrochloride on trough serum concentrations of concurrently administered digoxin in eight healthy volunteers. During the control phase of the study, volunteers were administered digoxin 0.25 mg/d for 13 days, and subsequently judged to be at steady state by serial determinations of digoxin serum concentrations. Twenty-four hour urine collections were done for creatinine clearance and urinary digoxin clearance determinations. Phase II of the study involved the addition of diltiazem hydrochloride 30 mg qid to the on-going, daily regimen of digoxin. After 14 days of concomitant therapy, steady-state trough digoxin concentrations were again determined, as well as creatinine clearances and urinary digoxin clearances. This investigation demonstrates that concomitant administration of diltiazem hydrochloride with digoxin results in significantly elevated steady-state trough digoxin concentrations (0.32 +/- 0.07 ng/ml increasing to 0.48 +/- 0.06 ng/ml, p less than 0.01). Urinary digoxin clearance decreased from 223.5 +/- 35.7 ml/min to 153.4 +/- 17.5 ml/min (p less than 0.05). Creatinine clearances were unaltered. A review of the current literature on this topic is included.

Adult↗
PubMed1981

Effect of activated charcoal on ethanol blood levels in dogs.

The effect of activated charcoal on ethanol blood levels following oral administration of ethanol was studied. Six healthy laboratory dogs were administered 2 ml/kg of 95% ethanol diluted to a 20% solution. Blood ethanol concentrations were measured at 0.5, 1.2, and 3 hours after dosing. After a one-week washout period, the same animals received an identical dose of ethanol preceded by 50 g of activated charcoal in a water slurry. Blood ethanol concentrations were again determined. Absorption of ethanol was significantly (p less than 0.005) inhibited by activated charcoal during the first hour after administration. Blood ethanol levels remained significantly lower (p less than 0.025) throughout the study in the activated charcoal group. Especially during the initial, critical hours of therapy, activated charcoal can significantly reduce the desired blood ethanol concentration required when ethanol is used as an emergency antidote for methanol or ethylene glycol poisonings. The use of activated charcoal is discouraged in poisoning emergencies where such oral-antidote therapy is necessary.

Absorption↗
PubMed1981

Effect of activated charcoal administration on acetylcysteine serum levels in humans.

The effect of orally administered activated charcoal on the absorption of acetylcysteine in three men was studied. Each of the three volunteers was given 140 mg/kg acetylcysteine as a single oral dose. Blood samples were taken at 0, 0.5, 1, 1.5, 2, 4, 6, and 8 hours after acetylcysteine ingestion. Following a one-week washout period, each subject was given orally 50 g of Activated Charcoal, USP, 15 minutes before a 140-mg/kg acetylcysteine oral dose. Blood samples were taken. Acetylcysteine content in the plasma was determined with a high-pressure ion-exchange chromatography system using a gold-mercury electrochemical cell. No statistically significant differences were found between total areas under the curves, peak concentrations, or time of peak concentrations of acetylcysteine given with or without charcoal. Although acetylcysteine absorption was delayed in two patients, the differences were not significant. These data suggest that acetylcysteine absorption is not impaired by activated charcoal administration. This conflicts with previously published in vitro data; therefore, it is recommended that activated charcoal should not be administered concomitantly with acetylcysteine as a usual procedure until more data are available.

Acetaminophen↗