bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacokinetics and Pharmacodynamics of Intravenous and Oral Azithromycin: Enhanced Tissue Activity and Minimal Drug Interactions
Authors: Rapp Robert P 
Published: March 2004

OBJECTIVE: To review the pharmacokinetics and pharmacodynamics of oral and intravenous azithromycin compared with other macrolide antibiotics, and to evaluate these differences and their relation to clinical effectiveness. DATA SOURCE: A MEDLINE search (1966–May 1998) was performed to identify applicable English-language clinical, animal, and microbiologic studies pertaining to pharmacokinetic and pharmacodynamic parameters. STUDY SELECTION: Relevant studies concerning microbiology, pharmacokinetics, tissue concentrations, pharmacodynamics, and the clinical effects of these parameters were selected. DATA SYNTHESIS: The structural modification that distinguishes the azalide antibiotics from the macrolide antibiotics is responsible for the pharmacokinetic and pharmacodynamic behavior of azithromycin, resulting in the high and sustained tissue and intracellular concentrations seen with this agent. Drug delivery to the site of infection by phagocytes and fibroblasts is the hallmark of azithromycin's tissue-directed pharmacodynamics, allowing for convenient once-daily, 5-day regimens for most infections that respond to oral therapy and 7–10 days for more serious infections requiring initial intravenous therapy. Metabolism is via hepatic pathways other than cytochrome P450, thus minimizing the risk of drug interactions. CONCLUSIONS: Compared with other macrolide antibiotics, the unique pharmacokinetic and pharmacodynamic features of azithromycin offer the potential for improved efficacy and safety from drug interactions. These attributes, combined with its once-daily dosing schedule, make azithromycin suitable for the treatment of many types of bacterial infection.
Selective Serotonin-Reuptake Inhibitor–Induced Movement Disorders
Authors: Gerber Patricia E , Lynd Larry D 
Published: March 2004

OBJECTIVE: To compile and evaluate all available data suggesting an association between selective serotonin-reuptake inhibitor (SSRI) administration and the occurrence of movement disorders, and to characterize these reactions in terms of onset, duration, treatment and outcome, and potential predisposing factors. METHODOLOGY: Reports of movement disorders were identified by conducting a comprehensive literature search that included tertiary adverse drug reaction resources, MEDLINE, EmBASE, Biological Abstracts, Current Contents, Reactions, ClinAlert, and International Pharmaceutical Abstracts. In addition, reports were solicited from the Canadian proprietary manufacturers of SSRIs, and from the Therapeutic Products Program of Health Canada. Each case was then classified according to the description of the movement disorder, based on predefined diagnostic criteria. RESULTS: A total of 127 published reports of SSRI-induced movement disorders were identified involving akathisia (n = 30), dystonia (19), dyskinesia (12), tardive dyskinesia (6), parkinsonism (25), and 15 cases of mixed disorders. Ten isolated cases of bruxism were identified. Ten additional reports could not be classified. Manufacturers of SSRIs provided 49 reports of akathisia, 44 of dystonia, 208 of dyskinesia, 76 of tardive dyskinesia, 516 of parkinsonism, and 60 of bruxism. Treatment strategies included discontinuation of the SSRI; dosage reduction; or the addition of a benzodiazepine, β-blocker, or anticholinergic agent. CONCLUSIONS: SSRI use appears to be associated with the development of movement disorders, as either a direct result of the drug or exacerbation of an underlying condition. Predisposing factors may include the use of neuroleptics, existing neurologic diagnoses, or preexisting movement disorders. Clinicians should be cognizant of the potential for these reactions, as prompt recognition and management is essential in preventing potentially significant patient morbidity.
Statistical Graphics in Pharmacokinetics and Pharmacodynamics: A Tutorial
Authors: Ette Ene I 
Published: March 2004

OBJECTIVE: To discuss the use of statistical graphics in the analysis of pharmacokinetics and pharmacodynamics data. METHODS: Information on graphic techniques and their application was retrieved from a MEDLINE search (January 1980–March 1997) of the English-language literature and bibliographic reviews of review articles and books. Data used to generate plots were extracted from some new drug applications submitted to the Food and Drug Administration and by simulation. DATA SYNTHESIS: In carrying out data analysis, we should look at data in several ways, construct a number of plots, and do several analyses, letting the results of each step suggest the next. The information from a plot should be relevant to the goals of the analysis. Thus, in choosing a graphic method, it is necessary to match the capabilities of the method to the need in the context of the application. For example, if linear relationships among variables in a set of multidimensional data are relevant, scatter plots such as the pairs plot with smoothing is likely to be more informative than other graphic methods. It is necessary to recognize what kinds of perceived structure are attributable to the data, and what kinds are artifacts of the display technique itself when using graphs for data analysis. CONCLUSIONS: Graphic techniques enable the data analyst to explore data thoroughly, look for patterns and relationships, confirm or disprove the expected, and discover new phenomena. An important element of statistical graphic techniques is flexibility, both in tailoring the analysis to the structure of the data and in responding to patterns that successive steps of analysis uncover. Statistical graphics can and should be used to enhance numeric statistical analyses.
Impact of Zidovudine Plus Lamivudine or Zalcitabine on Health-Related Quality of Life
Authors: Scott-Lennox Jane A , Mills Rose J , Burt Melinda S 
Published: March 2004

OBJECTIVE: To assess the impact of treatment with zidovudine plus lamivudine or zalcitabine on health-related quality of life (HRQOL) in patients with HIV. DESIGN: HRQOL assessments were conducted as part of a double-blind, randomized, 24-week (extended to 52 wk) efficacy and safety study. The Medical Outcomes Study HIV Health Survey (MOS-HIV), which assesses 10 physical and psychological domains of HRQOL, was self-administered by patients at baseline and at weeks 16, 32, 52, or at treatment discontinuation. SETTING: Twenty-one outpatient centers in the US, Canada, and Puerto Rico. PATIENTS: The study enrolled 254 HIV-positive patients (CD4+ 100–300 cells/mm3); 206 patients completed the MOS-HIV at baseline and at least once during treatment. Post hoc analyses stratified patients into two subgroups: AIDS (CD4+ <200 cells/mm3) and non-AIDS (CD4+ ≥200 cells/mm3). INTERVENTIONS: Patients received zidovudine 200 mg three times daily plus one of the following: lamivudine 150 mg twice daily, lamivudine 300 mg twice daily, or zalcitabine 0.75 mg three times daily. MAIN OUTCOME MEASURE: Change in MOS-HIV scores from baseline to last completed questionnaire. RESULTS: Following an average of 36 weeks of treatment, there were statistically significant differences across treatment groups in mean change scores on the physical functioning, role functioning, and vitality scales, with stable or increased (improved) scores in the zidovudine plus lamivudine 150 mg group and decreased scores in the zidovudine plus zalcitabine and zidovudine plus lamivudine 300 mg groups for most scales. Post hoc analyses found that in the non-AIDS subgroup, only the zidovudine plus lamivudine 150 mg group had increases in mean MOS-HIV scores (on 8 of 10 scales); in the AIDS subgroup, all but two MOS-HIV scores (in the zidovudine plus zalcitabine group) decreased in all three treatment groups. CONCLUSIONS: These results suggest that, of the three combination therapies studied, zidovudine plus lamivudine 150 mg was most likely to maintain or improve HRQOL in HIV-positive patients.
Cidofovir in the Treatment of Cytomegaloviral Disease
Authors: Kendle Julie B , Fan-Havard Patty 
Published: March 2004

OBJECTIVE: To review the clinical pharmacology and microbiology of cidofovir in the therapy of cytomegalovirus (CMV) disease. DATA SOURCES: Pertinent literature was identified via a MEDLINE search (October 1986–February 1997), and data from abstracts presented at recent scientific meetings were also included; unpublished information was provided by the manufacturer. STUDY SELECTION: Antiviral activity data were included if widely accepted methodology was used. All clinical data currently available from human studies were also included. DATA SYNTHESIS: Cidofovir is similar to ganciclovir in mechanism of action; however, cidofovir does not require viral enzymes for activation. Although the half-life of cidofovir in plasma is only 2.6 hours, the intracellular half-life may be much longer, allowing efficacy with biweekly maintenance dosing. In vitro, cidofovir appears to be equally or more effective than the other agents currently available for the treatment of CMV. In vivo, cidofovir appears to be effective in delaying the progression of CMV retinitis, although no clinical trials to date have directly compared cidofovir with either ganciclovir or foscarnet. Current intravenous dose recommendations are 5 mg/kg once weekly for two doses (induction), and then 5 mg/kg once every other week (maintenance). Since cidofovir is cleared almost entirely by the kidneys, dosage adjustments must be made in patients with impaired renal function. Disadvantages of cidofovir primarily include its risks of adverse drug reactions, such as nephrotoxicity, which is likely to occur in up to 50% of patients if appropriate preventative measures are not taken. Neutropenia and constitutional reactions to probenecid are also commonly encountered during the course of cidofovir therapy. CONCLUSIONS: Cidofovir is the first acyclic phosphonate nucleoside antiviral agent to be approved for general use in the US. In addition to delaying the progression of CMV retinitis, cidofovir may provide some protective benefits to patients at risk for developing the disease and may be active against certain strains of virus resistant to other currently available therapies. Another advantage of cidofovir is its infrequent dosage schedule, which may prove beneficial in patients who are not compliant with daily intravenous dosing regimens. When determining the appropriate treatment for a patient with CMV retinitis, the benefits of using cidofovir must be weighed carefully against the risk of potentially serious adverse effects.
Mibefradil: A New Class of Calcium-Channel Antagonists
Authors: Billups Sarah J , Carter Barry L 
Published: March 2004

OBJECTIVE: To describe the pharmacology, pharmacokinetics, and clinical efficacy of mibefradil compared with other agents used for hypertension and angina. DATA SOURCES: A MEDLINE search was performed for the period of January 1980 through September 1997 using the key terms mibefradil or Ro 40–5967. All articles written in English were considered for review. STUDY SELECTION AND DATA EXTRACTION: All clinical studies involving mibefradil were evaluated. Preclinical data were included if these data were not adequately represented in clinical (human) studies. DATA SYNTHESIS: Mibefradil is the first member of a new class of calcium-channel antagonists (CCAs) that block the T-type calcium channels. A long elimination half-life makes once-daily dosing feasible, and the drug's lack of negative inotropy and reflex tachycardia distinguishes it from other available CCAs. When administered at recommended dosages (50 or 100 mg once daily), mibefradil reduces blood pressure over 24 hours in patients with hypertension, improves exercise capacity, and relieves anginal symptoms in patients with chronic stable angina pectoris. CONCLUSIONS: Clinical studies have found that the antihypertensive effects of mibefradil are comparable with those of nifedipine, verapamil, and amlodipine, and more effective than those of diltiazem. These effects result from peripheral vasodilation and a slight reduction in heart rate. Selective vasodilation of the coronary vasculature makes it an effective antianginal agent when used alone or added to β-blocker therapy. Mibefradil demonstrates no significant effects on cardiac contractility, and no adrenergic stimulation resulting in reflex tachycardia. Therefore, it may have some advantages over currently available CCAs, especially in patients with congestive heart failure, although such advantages are unproven in published clinical trials. Ongoing clinical studies, including the Mortality Assessment in Congestive Heart Failure Trial (MACH-1) currently in progress, are needed to clarify mibefradil's place in cardiovascular therapy.
Home Blood Glucose Monitoring
Authors: Foster Shonda A , Goode Jean-Venable “Kelly” R , Small Ralph E 
Published: March 2004

OBJECTIVE: To provide a review of self-monitoring blood glucose including home blood glucose meters and patient education. DATA SOURCES: A MEDLINE search (January 1966–January 1998) was conducted to identify original and review articles. Search terms included self-monitoring blood glucose and blood glucose monitoring. Owner's manuals and package inserts were reviewed to determine specific characteristics for each glucose meter. DATA EXTRACTION: All current original and review articles about self-monitoring blood glucose and home blood glucose meters were included if they contained information about benefits of self-monitoring blood glucose, technology and performance of blood glucose meters, quality control, selection characteristics of blood glucose meters, and patient education. DATA SYNTHESIS: Self-monitoring of blood glucose has become an increasingly vital component of the care of the diabetic patient. Many glucose monitors are available with various features that may be confusing to pharmacists. Pharmacists need to be able to aid patients in the selection of an appropriate glucose meter and provide the education necessary for proper use and follow-up. Patient education is a key component in optimizing the potential benefits of self-monitoring. CONCLUSIONS: Self-monitoring of blood glucose, if used properly, can have a positive effect by increasing patient involvement in overall diabetes care. Pharmacists are accessible and can teach patients necessary skills that will enhance their ability to self-manage blood glucose.
A Mechanistic Approach to Antiepileptic Drug Interactions
Authors: Anderson Gail D 
Published: March 2004

OBJECTIVE: To describe the primary types of antiepileptic drug (AED) interactions by using a mechanistic approach. DATA SOURCES: A literature search was performed using MEDLINE and bibliographies of recent review articles and published abstracts. DISCUSSION: AEDs are associated with a wide range of drug interactions, including hepatic enzyme induction and inhibition and protein-binding displacement. Hepatic induction by AEDs affects the metabolism of a limited number of drugs with low therapeutic indices. Anticipation of induction interactions and careful clinical monitoring may alleviate potential problems. Most commonly used AEDs are eliminated through hepatic metabolism catalyzed by the cytochrome P450 (CYP) and uridine diphosphate glucuronosyltransferase (UGT) enzymes. Phenytoin, phenobarbital, and carbamazepine induce CYP and UGT enzymes. Lamotrigine is a weak inducer of UGT. Valproate is a broad-spectrum inhibitor of UGT enzymes, epoxide hydrolase, and CYP2C enzymes. Felbamate induces CYP3A4, but inhibits CYP2C19 substrates. Topiramate inhibits only CYP2C19 substrates. Ethosuximide, gabapentin, tiagabine, and vigabatrin are neither inducers nor inhibitors of drug metabolism. Hepatic enzyme inhibition usually occurs because of competition at the enzyme site. Knowledge of the specific metabolic enzymes involved in the metabolism of AEDs allows clinicians to predict potential interactions. CONCLUSIONS: By understanding the mechanisms of drug interactions, the pharmacist can play a key role in patient care by anticipating and preventing AED drug interactions.
Doxorubicin Dosage Guidelines in a Patient with Hyperbilirubinemia of Gilbert's Syndrome
Authors: Cupp Melanie Johns , Higa Gerald M 
Published: March 2004

OBJECTIVE: To reconcile dosage modification guidelines for doxorubicin in a patient with hyperbilirubinemia of Gilbert's syndrome (GS). CASE SUMMARY: A 62-year-old white man with concurrent diagnoses of large-cell non-Hodgkin's lymphoma and GS was treated with standard doses of a doxorubicin-containing chemotherapy regimen. No increase of end-organ toxicity was observed during four treatment cycles. DISCUSSION: The relative prevalence of GS coupled with the rising incidence of non-Hodgkin's lymphoma increases the probability that both disorders will be present in the same individual. A MEDLINE search (1966 through July 1997) revealed little, and often conflicting, information pertaining to drug metabolism and disposition in GS. In addition, no information has been reported regarding the metabolic fate of doxorubicin in these patients. It is important to emphasize that the lack of enhanced extramedullary toxicity in this patient is not conclusive evidence that the hepatic abnormality of GS had no effect on doxorubicin metabolism. CONCLUSIONS: Based on information regarding mechanisms for hepatic clearance, dosage modification of doxorubicin may not be necessary in hyperbilirubinemia of GS.
Cost-Effectiveness Analysis of Abciximab: A Canadian Hospital Perspective
Authors: Zed Peter J , Frighetto Luciana , Sunderji Rubina , Marra Carlo A 
Published: March 2004

OBJECTIVE: To assess the cost-effectiveness of abciximab therapy versus traditional practice in high-risk patients receiving percutaneous transluminal coronary angioplasty (PTCA) from a Canadian hospital perspective. DESIGN: A predictive decision analytic model using published clinical and economic evaluations, as well as costs of medical care in Canada. SUBJECTS: High-risk PTCA patients as defined by the Evaluation of c7E3 for Prevention of Ischemic Complications trial and the c7E3 Fab Antiplatelet Therapy in Unstable Refractory Angina trial. INTERVENTIONS: Two treatment strategies were compared: (1) abciximab 0.25 mg/kg intravenous bolus 10 minutes prior to PTCA followed by abciximab 10 4μg/min intravenous infusion for 12 hours after the procedure, and (2) no abciximab adjunctive therapy at the time of PTCA. Both treatment strategies were combined with intravenous heparin up to 100 units/kg bolus pre-PTCA followed by bolus doses for 1 hour after PTCA per the protocol. Cumulative outcomes were considered up to 6 months after initial PTCA. RESULTS: At 6 months, 29% of the patients in the abciximab treatment arm compared with 33% in the no abciximab arm achieved one of the primary events. The most common adverse event experienced was major bleeding at 4% in the abciximab treatment arm versus 1.6% in the no abciximab arm. The average cost per patient for each strategy was $3261 Can ($1 Can = $0.686 US) (abciximab arm) versus $2073 Can (no abciximab arm), resulting in an incremental cost-effectiveness ratio of $29 700 Can per event-free patient. In univariate sensitivity analyses, the only controllable factor that changed the results of the cost-effectiveness outcome was the cost of abciximab. CONCLUSIONS: Although the use of abciximab as an adjunct to PTCA results in a reduction in event rates in high-risk patients compared with traditional treatment, there is an increased cost associated with this strategy.
Thrombolytic Therapy: A Review of Its Use in Acute Myocardial Infarction
Authors: Bizjak Eric D , Mauro Vincent F 
Published: March 2004

OBJECTIVE: To review the literature on the use of thrombolytic agents in the pharmacotherapeutic management of acute myocardial infarction (AMI). DATA SOURCE: English-language clinical trials, reviews, and editorials derived from MEDLINE (January 1966–September 1997) and/or cross-referencing of selected articles. STUDY SELECTION: Articles that were selected best represent the clinical trials researching the role for thrombolytics in the therapy of AMI to improve morbidity and mortality. DATA SYNTHESIS: AMI is one of the leading causes of mortality in the US. Following supportive data that the most common cause of an AMI is an intracoronary thrombus, clinical investigation has demonstrated that intravenous thrombolytic agents improve survival rates in patients who experience an AMI. Several clinical trials have been conducted to determine whether one thrombolytic agent is superior to others with respect to improving mortality. At present, only the first Global Use of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO-I) trial has reported any statistically significant difference in mortality rate. In this trial, “front-loaded” alteplase induced a statistically significant (p < 0.001) 1% absolute reduction in 30-day and 1-year mortality compared with streptokinase. This has led to alteplase being the preferred thrombolytic at many US institutions. However, the results of GUSTO-I have been questioned by some on the basis of either study design or clinical significance. CONCLUSIONS: Thrombolytic agents have secured a place in the treatment of AMI due to their well-proven reduction in mortality rates. In general, comparative trials have demonstrated minimal differences in efficacy among these agents. Probably just as important as choosing which thrombolytic agent to use is ensuring that a patient experiencing an AMI is administered thrombolytic therapy unless a contraindication to receive such therapy exists in the patient and/or the patient is a candidate to receive an emergent intracoronary procedure. Trials also indicate that the sooner thrombolytics can be administered, the greater the benefit to the patient.
State Pharmacy Regulators' Opinions on Regulating Pharmaceutical Care Outcomes
Authors: Nau David P , Brushwood David B 
Published: March 2004

OBJECTIVE: To examine the opinions of state pharmacy regulators regarding responsibility for the outcomes of drug therapy, and approaches that might be taken to regulate for pharmaceutical care outcomes. DESIGN: Surveys were sent to the executive secretaries of state pharmacy boards. The executive secretaries were encouraged to seek input from other board staff and board members in formulating a response. Reminder postcards were sent to all subjects 1 week after the initial mailing. MEASURES: The survey instrument was divided into three sections. The first section identified 10 approaches that state boards could use to regulate for outcomes and asked subjects to indicate the utility of each. The second and third sections asked the subjects to determine the extent to which pharmacies and pharmacists, respectively, should be responsible for outcomes potentially related to pharmaceutical care. RESULTS: Forty-one usable surveys were returned. All approaches to regulation were viewed as potentially useful, and scores for three approaches indicated that they would be consistently helpful for effective regulation of pharmaceutical care outcomes. The pharmacy was viewed as solely responsible for poor outcomes related to systems deficiencies, a lack of self-assessment, inadequate references, equipment, and technician support. Pharmacists were assigned greatest responsibility for outcomes related to prescription filling, and less responsibility for outcomes related to patient care. However, there was considerable variation in responses to many of the items, reflecting the diverse opinions of pharmacy regulators on these issues. CONCLUSIONS: While pharmacy regulators appear open to some outcomes-oriented approaches to regulation, there is no clear consensus on responsibility for pharmaceutical care outcomes.