Efficacy and Clinical Value of Commonly Used Ingredients in Pain Management Compounds: A Literature Review.

The need for continued improvement in pain management is growing. This review is aimed towards identifying the literature regarding clinical and therapeutic value of the commonly used ingredients in pain management compounds: lidocaine, tetracaine, ketoprofen, ketamine, and gabapentin. Prospectively, future studies should be conducted to identify the exact benefits and side effects of compounded pain management therapies, such that these compounds can be effectively utilized when deemed appropriate.

Efficacy and Clinical Value of Commonly Used Ingredients in Pain Management Compounds: A LITERATURE REVIEW.

The need for continued improvement in pain management is growing. This review is aimed towards identifying the literature regarding clinical and therapeutic value of the commonly used ingredients in pain management compounds: lidocaine, tetracaine, ketoprofen, ketamine, and gabapentin. Prospectively, future studies should be conducted to identify the exact benefits and side effects of compounded pain management therapies, such that these compounds can be effectively utilized when deemed appropriate.

Efficacy and clinical value of commonly compounded hormone replacement therapy: a literature review.

Hormone replacement therapy compounding is an important practice in the field of pharmacy. The efficacy and clinical value of its use have sometimes been controversial in the current literature. This study focused on providing a summary review of some of the literature regarding clinical and therapeutic value of the commonly used ingredients in hormone replacement therapy compounds, to include progesterone, pregnenolone, estrogen, dehydroepiandrosterone, and testosterone.

Review of the pharmacodynamics of antibiotic use in animal food production.

Much attention has been focused on food-producing animals as a potential source of antimicrobial-resistant bacteria in humans. These efforts, however, have been met with continued debate and disagreement within the medical, veterinary, and regulatory communities as to whether the veterinary use of antimicrobials is a significant risk factor for the development of antimicrobial-resistant pathogens. As such, it is the purpose of our paper to assess factors involved in the pharmacokinetics and pharmacodynamics of antibiotic use in animal food production. We conclude that, based on the number of variables involved and the lack of definitive studies, it is difficult to determine the AUC:MIC for antimicrobials. Unfortunately, we are left only with general principles that indicate that low doses of antibiotic tend to select for bacterial resistance, and high doses tend to kill the microorganism. In the case where animal-associated pathogens cause human disease, those practices that target adequate exposures (AUC:MIC) of antimicrobials should continue, whereas those practices producing low exposures should be modified or halted to prevent the emergence and spread of resistant organisms.

Pharmacodynamics of moxifloxacin and levofloxacin at simulated epithelial lining fluid drug concentrations against Streptococcus pneumoniae.

Recent clinical failures associated with levofloxacin treatment for Streptococcus pneumoniae infections and growing evidence of frequent mutations in the isolate population have led to increased concerns regarding fluoroquinolone resistance. Our objective was to characterize the efficacies of levofloxacin and moxifloxacin against various genotypes of S. pneumoniae after simulated bronchopulmonary exposures. An in vitro model was used to simulate a levofloxacin concentration of 500 mg and a moxifloxacin concentration of 400 mg, which were previously determined to be the concentrations in the epithelial lining fluid of older adults receiving once-daily dosing. The effects of the drugs were tested against six S. pneumoniae containing various mutations. Bacterial density and resistance were quantitatively assessed over 48 h. The S. pneumoniae isolate with no mutation displayed a 4-log reduction in CFU after treatment with both agents and did not develop resistance. Isolates containing the parC or parE mutation or both mutations regrew and developed resistance when they were exposed to levofloxacin, despite an unbound area under the concentration-time curve (AUC):MIC ratio of approximately 100. When the isolate containing the parC and gyrA mutations was exposed to levofloxacin, there was a half-log reduction in the number of CFU compared to that for the control, but the isolate subsequently regrew. Likewise, levofloxacin did not kill the isolate containing the parC, gyrA, and parE mutations. Moxifloxacin sustained the killing of all bacterial isolates tested without the development of resistance. Levofloxacin did not sustain bacterial killing and did not prevent the emergence of further resistance in mutants with the parC or parE mutation or both mutations, even though an unbound AUC:MIC ratio for exposure well above the breakpoint of 30 to 40 established in the literature for S. pneumoniae was maintained. Moxifloxacin was effective against all isolates tested, despite the presence of isolates with two- and three-step mutations, for which the MICs were increased.

Pharmacodynamics of meropenem and imipenem against Enterobacteriaceae, Acinetobacter baumannii, and Pseudomonas aeruginosa.

STUDY OBJECTIVE: To compare the pharmacodynamics of meropenem and imipenem, both administered as 500 mg every 6 hours, against populations of Enterobacteriaceae, Acinetobacter baumannii, and Pseudomonas aeruginosa. DESIGN: Ten thousand-subject Monte Carlo simulation. INTERVENTION: Variability in total body clearance (ClT), volume of distribution as calculated by the terminal elimination rate (Vdbeta), and minimum inhibitory concentration (MIC) distributions (Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Serratia marcescens, A. baumannii, P. aeruginosa) were derived from the literature for both meropenem and imipenem. For the free drug concentrations, the percentage of the dosing interval that the drug concentrations remain above the MIC (%T>MIC) for each carbapenem-bacteria combination was calculated for 10,000 iterations, substituting a different ClT, Vdbeta, fraction of unbound drug, and MIC into the equation each time based on the probability distribution for each parameter. Probabilities of attaining targets of 30%, 50%, and 100% T>MIC were calculated. MEASUREMENTS AND MAIN RESULTS: Meropenem free drug %T>MIC exposure was significantly greater than that of imipenem against Enterobacteriaceae and P. aeruginosa, whereas imipenem exposure was greater for A. baumannii. For both agents, free drug %T>MIC exposure was greatest against Enterobacteriaceae and less for A. baumannii and P. aeruginosa. Probabilities of target attainment for 30% and 50% T>MIC were similar between drugs for most bacteria. At 100% T>MIC, meropenem target attainments were greater than those of imipenem against Enterobacteriaceae and P. aeruginosa, and imipenem attainment was higher for A. baumannii. CONCLUSION: The probability of attaining lower pharmacodynamic targets for most gram-negative bacteria is similar for these carbapenems; however, differences become apparent as the pharmacodynamic requirement increases. Further study of the benefits of achieving this pharmacodynamic breakpoint with a higher probability of attaining targets is necessary.

Cost analysis of continuous versus intermittent infusion of piperacillin-tazobactam: a time-motion study.

The time and associated costs (drug, labor, supply) of administering a continuous versus an intermittent i.v. infusion of piperacillin-tazobactam were compared. The total labor cost was calculated for each regimen based on the time required for nurses, pharmacists, and pharmacy technicians to either prepare or administer the drug, according to their standard responsibilities. Thirty timed observations were made for each of the dosing formulations. Observations were conducted on separate occasions for at least four different nurses, pharmacists, and pharmacy technicians per formulation. Labor costs were calculated by multiplying the mean times recorded by the average U.S. hourly wages and local wages for these health professionals and extrapolated to encompass a 24-hour period of drug administration. The average wholesale price and hospital contract price of piperacillin-tazobactam were used to calculate the costs of both intermittent and continuous infusions. The costs for all items used in drug preparation and administration were also calculated for supplies. Basic descriptive statistics were used to evaluate the costs of the time needed to prepare and administer the different regimens. Drug acquisition costs accounted for the largest percentage of the total cost for all regimens. Analysis of labor costs revealed that nursing time accounted for the majority of the labor costs, with continuous infusion regimens being the least time-consuming and least costly administration method. Continuous-infusion regimens were more cost-efficient when evaluated on a daily basis and for the total cost of 5- and 10-day treatments. The use of continuous infusion as a means of administering piperacillin-tazobactam maximized the drug's pharmacodynamics and was more cost-efficient than intermittent infusion of the drug.

Pleconaril, a novel antipicornaviral agent.

Despite the availability of therapy for selected symptoms, no specific antiviral agents are available to treat or prevent infections due to the viruses of the Picornaviridae family--rhinoviruses and enteroviruses. Characterization of the three-dimensional structure of picornaviruses in the 1980s allowed development of compounds targeted at the virus itself. Pleconaril is a novel, orally available, systemically acting molecule whose pharmacokinetics are characterized by a two-compartment open model with first-order absorption and with a safety profile similar to that of placebo. It shows promising results in treatment of picornaviral respiratory tract infections, meningitis, and other life-threatening infections.