Does using a mouthwash instead of water improve the oropharyngeal removal of inhaled flovent (fluticasone propionate)?

Rinsing the mouth with water is recommended to remove inhaled corticosteroid (ICS) deposited on the oropharyngeal mucosa. Given the lipophilicity of fluticasone propionate (FP), an ethanol-based mouthwash was hypothesized to be superior to water. This study's purpose was to compare the effectiveness of water versus Listerine (Warner Lambert, Lititz, PA) in removing FP from the oropharyngeal mucosa. Asthma patients were randomly assigned water or a Listerine-rinsing vehicle. A 440-microgram dose of FP was inhaled. After the second puff, patients rinsed for 30 seconds with 20 mL of the assigned agent and then repeated the process, spitting each "wash" into the same cup. At visit 2, patients used the alternate vehicle and repeated the procedure. Samples were frozen until analyzed using liquid chromatography/mass spectrophotometry (lower limit of detection 0.067 microgram/mL). Thirty-six patients (mean age, 44 years; 66% female) participated. Mean inhaler technique score was 11.3 (scale of 1-12). Eighty-three percent used the closed-mouth technique. The mean concentration of FP removed by Listerine was not statistically different than that removed by water, 1.67 micrograms/mL (range, 0.067-4.195 micrograms/mL) and 1.42 micrograms/mL (range, 0.067-5.107 micrograms/mL), respectively, and the total milliliter returned was assumed to be 40 mL. Regression analysis using sex, age, and inhaler technique showed no statistical relationship with the amount of FP removed. Therefore, Listerine was not more effective than water in removing FP from the oropharyngeal mucosa (p = 0.53). Thus, water is an adequate rinsing vehicle for removal of ICS deposited on the oropharyngeal mucosa. Other factors besides the rinsing vehicle are strong factors in determining the amount of drug removed.

Effect of salmeterol on patients' adherence to their prescribed refills for inhaled corticosteroids.

BACKGROUND: Optimal treatment for persistent asthma requires multiple classes of medication, including antiinflammatory agents and bronchodilators. Inhaled corticosteroids are the most effective antiinflammatory agents available and are recommended by recent guidelines as first-line treatment. Salmeterol, a long-acting inhaled bronchodilator, is recommended as adjunctive therapy to inhaled corticosteroids. Non-adherence to prescribed medication is prevalent and has been implicated in asthma exacerbations. Salmeterol's benefits in terms of asthma control are readily perceived by patients whereas the benefits of inhaled corticosteroid therapy may be less apparent. OBJECTIVE: To evaluate whether the addition of salmeterol to a medication regimen affects patient adherence to prescription refills for inhaled corticosteroids. METHODS: A retrospective medical chart and pharmacy claims record review before and after the addition of salmeterol was used. Medication adherence rates were calculated for 67 patients requiring inhaled corticosteroids for at least 8 months before and after the addition of salmeterol. RESULTS: Adherence with inhaled corticosteroid therapy before (49.7% +/- 29.3%) and after (56.5% +/- 28.6%) the introduction of salmeterol was not significantly different (P = .0785, pre versus post). Adherence with salmeterol was significantly higher (58.7% +/- 28.3%) than inhaled corticosteroids at baseline (P = .0202), but not with concurrent use. Dosing frequency of inhaled corticosteroid administration was not a significant factor in adherence, but increasing age was (r = 0.41788, P = .0048). CONCLUSIONS: The addition of salmeterol does not adversely affect the adherence rates to prescription refills for prescribed inhaled corticosteroid therapy. On average, important antiinflammatory treatment should not be supplanted with salmeterol if prescribed in combination.

Zafirlukast: the first leukotriene-receptor antagonist approved for the treatment of asthma.

OBJECTIVE: To review the pharmacology, pharmacokinetics, clinical efficacy, and adverse effects of zafirlukast. Therapeutic issues regarding the use of a leukotriene-receptor antagonist as prophylactic antiinflammatory therapy for asthma are also discussed. DATA SOURCES: A MEDLINE search was conducted to identify pertinent literature, including preclinical trials, clinical trials, and reviews. Pharmacokinetic and dosing information were abstracted from the product labeling. STUDY SELECTION: All available published articles describing double-blind, placebo-controlled trials of both oral and aerosol zafirlukast in patients with asthma or rhinitis were reviewed. These included single-dose studies with zafirlukast against exercise, allergen, leukotriene D4 (LTD4), and platelet-activating factor (PAF) challenges, and 6- and 13-week trials in patients with asthma. Studies describing clinical trials with long-term use or comparisons with other asthma medications as reported in abstracts are also included. DATA EXTRACTION: Information on the safety and efficacy of zafirlukast from single- and multiple-dose studies was evaluated on the basis of statistical significance relative to placebo treatment. DATA SYNTHESIS: Zafirlukast, a potent and selective antagonist of the cysteinyl leukotriene receptor, blocks leukotriene-mediated pathologic events in both experimental animal and clinical disease models. Zafirlukast antagonizes LTD4-, PAF-, and exercise-induced bronchoconstriction, and blocks both early- and late-phase responses following allergen provocation in patients with atopic asthma. Greater efficacy is noted following oral administration than with aerosol dosing, presumably because of the enhanced delivery of drug when ingested rather than inhaled. CONCLUSIONS: Zafirlukast is the first orally active leukotriene-receptor antagonist approved by the Food and Drug Administration for the prophylactic and chronic treatment of asthma. Since the leukotrienes play an important role in the underlying inflammatory processes of asthma, zafirlukast represents a new antiinflammatory option available in an oral dosage form. It is clear that this agent has therapeutic activity in patients with asthma, but its effectiveness relative to other antiasthma medications still needs confirmation. Data from clinical studies support the use of zafirlukast as first-line therapy in patients with mild-to-moderate asthma. Further research is needed to establish its role as an add-on agent for patients with severe asthma, aspirin-sensitive asthma, and both allergies and asthma. In addition to having a favorable safety and efficacy profile, zafirlukast has the advantage of being an oral agent with twice-daily dosing; these attributes offer the potential for greater patient adherence to pharmacotherapy and, thereby, improved control of asthma symptoms.

A cost-effectiveness analysis of breath-actuated metered-dose inhalers.

Managed care plans evaluate therapeutic alternatives to identify the most cost-effective medications for asthma. Three hundred one patients with asthma were randomized to receive the beta-agonist pirbuterol from either a manually operated metered dose inhaler (MDI) or a breath-actuated inhaler (BAI). Cost effectiveness was evaluated by the cost of the beta-agonist medication used and patient-reported outcomes. No significant differences between the two groups appeared in baseline or follow-up outcomes, which were assessed by self-reported health status and spirometry. However, patients receiving pirbuterol from BAIs used 23% less than those patients who received the drug from MDIs.

Comparison of patients' compliance with prescribed oral and inhaled asthma medications.

BACKGROUND: Noncompliance with medications is one of the most serious problems facing health care today. However, methods to measure compliance have many limitations. METHODS: To measure specific drug compliance and dosing frequency of two asthma medications, we used medical records data and pharmacy claims data from 276 patients who had concurrent prescriptions for inhaled anti-inflammatory agents and oral theophylline. Patients were randomly selected from the pharmacy claims data files of a health maintenance organization. The patients' medical records were reviewed, and records that did not contain clear documentation of the medication, dose, and dosing frequency were excluded. Data from the remaining 119 medical records were compared with data from pharmacy claims to calculate compliance rates for each medication. RESULTS: Our calculations showed that patients were significantly more compliant with prescribed theophylline medication than with two inhaled anti-inflammatory medications (P = .0001). No significant differences in compliance were found relative to prescribed dosing frequency (twice daily or less compared with three times daily or more) for either medication (P = .6517). CONCLUSIONS: Comparison of medical record data with pharmacy claims data is an effective indirect measure of patients' compliance with prescribed oral theophylline and inhaled anti-inflammatory agents. Additional interventions must be pursued for patients with asthma regarding adherence to regimens for their prescribed inhaled anti-inflammatory agents.

Evaluation of the Autohaler actuator: the effect of written patient instructions on correct use.

The Autohaler actuator is a breath-actuated device designed by 3M Pharmaceuticals. The objective of this study was to measure and improve the effectiveness of the device's package insert instructions (PII). Using only the PII for guidance, 5 of 20 (25%) subjects failed to trigger the device. The PII were revised based on the subject's performance and suggestions. Using the revised PII, only 1 of 20 (5%) different subjects failed to trigger the device. These results indicate that relatively minor modifications to instructions can result in significant improvements in patient use. Eighty-five percent of the participants thought the device was easier to use than a metered-dose inhaler.

Disposition of cefpodoxime proxetil in hemodialysis patients.

The disposition of cefpodoxime after single, oral 200-mg doses of cefpodoxime proxetil (cefpodoxime equivalents) was investigated in an open-label study of six patients with end-stage renal disease currently maintained on hemodialysis. Subjects were randomly assigned to one of two treatment groups, which differed in the sequence of the interdialytic and intradialytic periods. Doses were separated by at least 2 weeks. Blood samples were serially collected for 48 hours after each treatment; if obtainable, urine was also collected over this same period. During the intradialytic period, hemodialysis was scheduled to begin approximately 3 hours after dosing, and dialysate was collected before and until the end of dialysis. Average cefpodoxime elimination half-life for the interdialytic period was 18.0 +/- 6.5 hours; apparent total body clearance was 28.6 +/- 13 mL/minute. The half-life during hemodialysis, 2.66 +/- 0.74 hours, was considerably shorter than that after hemodialysis, 19.2 +/- 3.5 hours, in the intradialytic period of the study. Hemodialysis clearance of cefpodoxime was 120 +/- 31 mL/minute, which was 57.1 +/- 13% and 71.7 +/- 25% of the hemodialysis clearance for urea nitrogen and creatinine, respectively. The 2.86 +/- 0.25 hour hemodialysis session removed 22.4 +/- 2.9% of the administered dose, as assessed by cefpodoxime recovery in dialysate. A maximum rebound in cefpodoxime plasma concentration of 0.41 +/- 0.33 mcg/mL was observed, at about one-half hour after the end of hemodialysis. Based on these results, dosage adjustment is not required, but extension of the dosing interval is warranted.(ABSTRACT TRUNCATED AT 250 WORDS)

Single-dose pharmacokinetics of piperacillin and tazobactam in patients with renal disease.

Tazobactam is an irreversible inhibitor of many beta-lactamases. In combination with piperacillin, tazobactam exhibits synergy against many beta-lactamase-producing bacteria. The pharmacokinetics of piperacillin and tazobactam were evaluated in eight normal volunteers and in 52 patients with renal dysfunction. Plasma and urine were obtained for up to 30 hours after an infusion of piperacillin and tazobactam (3 and 0.375 gm, respectively). Dialysate samples were collected from patients undergoing dialysis. Piperacillin and tazobactam concentrations were determined by high-performance liquid chromatography. Noncompartmental methods were used for pharmacokinetic analysis. Piperacillin and tazobactam total body clearance, area under the curve, and terminal elimination rate correlated with renal function. Hemodialysis removed 31% and 39% of piperacillin and tazobactam, respectively. During continuous ambulatory peritoneal dialysis, 5.5% of the piperacillin and 10.7% of the tazobactam was recovered in the dialysate over 28 hours. Peak plasma concentrations of both drugs increased minimally with decreasing creatinine clearance. Dosage alterations for creatinine clearance values less than 40 ml/min are recommended.

Disposition of cefpodoxime proxetil in healthy volunteers and patients with impaired renal function.

The disposition of cefpodoxime in 24 subjects with various degrees of renal function after administration of a single oral dose of 200 mg of cefpodoxime proxetil (equivalent to 200 mg of cefpodoxime activity) was studied. Subjects were assigned to one of four groups (six per group): group I, normal renal function (creatinine clearance [CLCR], greater than ml/min); group II, mild renal impairment (CLCR, 50 to 80 ml/min); group III, moderate renal impairment (CLCR, 30 to 49 ml/min); or group IV, severe renal impairment (CLCR, 5 to 29 ml/min). Although cefpodoxime terminal elimination half-life in group I (2.55 +/- 0.25 h [mean +/- standard deviation]) was not significantly different from that in group II (3.53 +/- 0.74 h), the half-life values for group III (5.90 +/- 1.67 h) and group IV (9.80 +/- 1.21 h) were significantly prolonged compared with those of group I. The mean absorption rate constant was similar among groups and ranged from 0.68 to 0.85 h-1. All groups exhibited absorption lag-times which were comparable (0.30 to 0.41 h), and the apparent volume of distribution was similar among groups. Cefpodoxime apparent total body clearance (CLP/F) values in groups II, III, and IV (132 +/- 29, 112 +/- 41, and 55.7 +/- 9.9 ml/min, respectively) were significantly lower than that in group I (238 +/- 44 ml/min). Cefpodoxime CLP/F was positively correlated with CLCR (r2 = 0.79; P less than 0.05): CLP/F = (1.9 CLCR) + 18.4. Renal clearance also declined with decreasing renal function. Adjustments in cefpodoxime organism and on the site and severity of infection. Simulated plasma concentration-time data from this study suggest that 200 mg of cefpodoxime proxetil administered every 12 to 24 h to subjects with CLcr between 30 and 49 ml/min and 200-mg dose taken every 24 h by subjects with CLcr between 5 and 29 ml/min will maintain cefpodoxime concentration in plasma similar to those in subjects with normal renal function who receive a standard dosage mg every 12 h.

Pharmacokinetics of ceftibuten-cis and its trans metabolite in healthy volunteers and in patients with chronic renal insufficiency.

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 (CLCR). The apparent total body clearance (CLP/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 (CLCR, 5 to 29 ml/min; group IV) and moderate (CLCR, 30 to 49 ml/min; group III) renal insufficiency than in those with mild renal insufficiency (CLCR, 50 to 80 ml/min; group II) or normal renal function (CLCR, greater than 80 ml/min; group I). A significant correlation was observed between CLCR and ceftibuten-cis CLP/F. The mean apparent steady-state volume of distribution (V beta/F) of ceftibuten-cis ranged from 0.21 to 0.24 liter/kg in subjects in group I, II, III, and IV. V beta/F was significantly greater in the group V subjects with end-stage renal disease (V beta/F, 0.39 +/- 0.27 liters/kg). These changes in V beta/F cannot be separated from possible changes in bioavailability. The maximum concentration of ceftibuten-trans in plasma was significantly higher and occurred significantly later in group IV subjects than it did in subjects in the other groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Isepamicin disposition in subjects with various degrees of renal function.

The disposition of isepamicin, an investigational aminoglycoside antibiotic, was evaluated in 30 subjects with various degrees of renal function. The subjects were divided into five groups: those with normal renal function (creatinine clearance [CLCR], greater than 80 ml/min/1.73 m2), those with mild renal insufficiency (CLCR, 50 to 80 ml/min/1.73 m2), those with moderate renal insufficiency (CLCR, 30 to 49 ml/min/1.73 m2), those with severe renal insufficiency (CLCR, 5 to 29 ml/min/1.73 m2), and those maintained on hemodialysis (CLCR, less than 5 ml/min/1.73 m2). Subjects on hemodialysis were studied both during hemodialysis and during an interdialytic period. The volumes of distribution of isepamicin were not significantly different among the five groups of patients. The total body clearance (CLP) and renal clearance (CLR) of isepamicin significantly decreased as CLCR decreased. The CLP of isepamicin and CLCR were significantly related [(COP = 0.391.[CLCR] + 1.83; r2 = 0.878)]. Nonrenal clearance of isepamicin did not differ between groups. Hemodialysis augmented the CLP of isepamicin by approximately 25-fold. The amount of isepamicin recovered in the dialysate was 60.6 +/- 15.8% of the dose administered. The maximal rebound of the isepamicin concentration in plasma after cessation of hemodialysis was observed at 0.78 +/- 0.7 h. Concentrations in plasma increased 32.7 +/- 22.9% over that measured at the end of hemodialysis. These data indicate that dosage adjustments are necessary in subjects with decreased renal function.