Zanamivir and oseltamivir: two new options for the treatment and prevention of influenza.

BACKGROUND: Influenza infection is responsible for thousands of hospitalizations and deaths in the United States each year. Until recently, management options were limited to vaccination or use of the antiviral agents amantadine and rimantadine. Two antiviral drugs, zanamivir and oseltamivir, have recently been approved by the US Food and Drug Administration for the treatment of influenza A and influenza B. OBJECTIVE: This article reviews the published data on the pharmacology and clinical utility of zanamivir and oseltamivir in the treatment and prevention of influenza A and influenza B illness. METHODS: To identify relevant literature, a search of MEDLINE, International Pharmaceutical Abstracts, and the Iowa Drug Information Service was conducted for the period from 1969 to 2000. The search terms used were influenza, neuraminidase, zanamivir, oseltamivir; amantadine, and rimantadine. The reference lists of the articles so obtained were used to identify additional publications. RESULTS: Zanamivir and oseltamivir inactivate viral neuraminidase, an enzyme responsible for cleaving sialic acid residues on newly formed virions as they bud off from the host cell. This inhibition results in aggregation of virions on the surface of the host cell, which limits the extent of infection and speeds recovery from illness. Clinical studies have shown that neuraminidase inhibitors can decrease the median duration of influenza-related symptoms by approximately 1 day if initiated within 48 hours of the onset of symptoms of influenza. CONCLUSIONS: Evidence supports the use of zanamivir and oseltamivir in the treatment of influenza; however, additional studies are needed to clarify their utility and tolerability in pediatric and high-risk patients, as well as their utility in the prevention of influenza.

Pharmacokinetics of vancomycin when administered during high flux hemodialysis.

This study was undertaken to evaluate the pharmacokinetics of relatively high-dose vancomycin when administered during high-flux hemodialysis using a polysulfone membrane (F-80, Fresenius). Five noninfected, anuric patients received a single dose of 25 mg/kg of vancomycin infused during hemodialysis at a rate of one gram per hour and timed such that the end of the infusion coincided with the end of dialysis. Blood samples were drawn during the infusion, up to six hours after the end of dialysis and then prior to the next three dialysis treatments. Spent dialysate was collected during the infusion. Samples were analyzed using the EMIT assay. The percent of vancomycin lost during the first dialysis session ranged from 39.1 to 55.1% (mean, 45.7+/-6.4). The concentration of vancomycin at 6 hours after hemodialysis ranged from 18.2 to 45.1 mg/L (mean, 29.6+/-10.0 mg/l). Dialysis clearance ranged from 96.1 to 158.1 ml/min (mean, 130.7 +/-30.0 ml/min). One week after dosing, serum concentrations ranged from 8.14 mg/l to 10.1 mg/l (mean, 9.0+/-1.0 mg/l). This study suggests than an initial dose of 25 mg/kg of vancomycin, given during high-flux dialysis, may provide adequate serum concentrations in anuric hemodialysis patients for up to seven days. This dosing scheme reduces inconvenience to the patient and staff, and potentially can reduce nursing costs associated with post-dialysis administration; its cost is minimal. At this point, subsequent dosing is best determined by therapeutic drug monitoring.