Piperacillin-Tazobactam Pharmacokinetics in Patients With Intraabdominal Infections

Study Objective . To determine the appropriate compartmental and noncompartmental pharmacokinetic parameters for intravenous piperacillin and tazobactam. Design . Sequential selection of patients entered into a randomized, open-label clinical efficacy trial. Setting . Los Angeles County-University of Southern California Medical Center. Participants . Sequential sample of 18 patients admitted for intraabdominal infections and consented into a comparative antibiotic trial. Interventions . Patients received piperacillin 4 g plus tazobactam 500 mg by intravenous intermittent infusion every 8 hours. Measurements and Main Results . The estimated noncompartmental pharmacokinetic parameters (mean ± SD) for piperacillin and tazobactam, respectively, were as follows: maximum concentration in plasma 218.7 ± 48.9 μg/ml and 27.8 ± 9.1 μg/ml; half-life 1.07 ± 0.22 hours and 1.00 ± 0.27 hours; elimination rate constant 0.67 ± 0.13 hr⁻¹ and 0.73 ± 0.18 hr⁻¹; area under the concentration-time curve from zero hour to infinity 288.5 ± 71.25 mg·hr/L and 36.3 ± 9.55 mg·hr/L; total plasma clearance 14.75 ± 3.93 L/hour and 14.78 ± 4.39 L/hour; renal clearance 5.69 ± 1.94 L/hour and 7.85 ± 3.37 L/hour; volume of distribution at steady state 21.00 ± 4.18 L and 22.47 ± 8.27 L; and mean residence time 1.72 ± 0.29 hours and 1.79 ± 0.35 hours. Conclusion . Our findings were similar to those in other surgical patient models. The two-compartmental model best described piperacillin and tazobactam disposition in our patients. Bayesian analyses of the two-compartment models of piperacillin and tazobactam were able to predict trough, peak, and 2-hour postadministration levels without bias.     

Effects of androgens on bone in men and women

Although the beneficial effects of estrogen on bone have been proven in multiple well-designed clinical trials, with respect to testosterone and androgens, the data are less definitive. Testosterone appears to have a role in the development and maintenance of bone mass; however, the mechanism by which androgens exert their effects on bone is still not clearly understood. Despite the increasing use of testosterone supplementation in men and women for the prevention and treatment of osteoporosis, in sufficient evidence exists to support the widespread use of these agents for this indication at this time. The data supporting the beneficial effects of testosterone on bone mineral density are more convincing in hypogonadal men than in men with normal testosterone levels, or in women. The transdermal route of administration is often preferred for testosterone therapy because it avoids the first-pass metabolism associated with oral formulations and the pain experienced with intramuscular injections. Other androgens, including an abolic steroids and dihydroepiandrosterone, have also been used. In addition to monitoring for therapeutic response on initiation of androgen therapy, assessment for potential adverse events should be implemented. This should include assessment for adverse effects on the liver and alterations in the lipid profile in both men and women. Men should also be monitored for prostate growth, gynecomastia, priapism, decreased libido, and erythrocytosis, whereas women should be monitored for virilizing effects. Ongoing research into the pathophysiology and clinical effects of testosterone on bone will provide more insights regarding the utility of androgens in these populations.     

Use of Probiotics in the Management of Chemotherapy‐Induced Diarrhea: A Case Study

Gastrointestinal disturbances (particularly diarrhea) are often induced in response to cancer treatments such as chemotherapy or radiation. Oral chemotherapeutic agents can induce diarrhea by damaging the intestinal lining. Two common oral drugs used in cancer treatment that are known to have gastrointestinal side effects are capecitabine and lapatinib. In this brief communication, the authors discuss a case study of a stage IV breast cancer patient whose chemotherapy‐induced diarrhea was treated successfully with a multispecies combination of probiotics. This is a unique study in which grade 3 chemotherapy‐induced diarrhea (characterized by 7–9 stools per day and associ ated with incontinence and abdominal cramping) was treated with only a multispecies combination of probiotics. Probiotics have been used to treat diarrhea in patients with irritable bowel syndrome, ulcerative colitis, pouchitis, and Crohn's disease. More recently, probiotics have been used to treat chemotherapy‐induced diarrhea in colon cancer patients. This case study demonstrates that the probiotics can also be used to treat severe cases of chemotherapy‐induced diarrhea in breast cancer patients. The use of different probiotics in gastrointestinal diseases is an increasingly important area of study, and more research into this area is needed. This study demonstrates that probiotics should be considered for advanced breast cancer patients with chemotherapy‐induced diarrhea.     

Budesonide Inhalation Powder: A Review of Its Pharmacologic Properties and Role in the Treatment of Asthma

Budesonide inhalation powder, available as Pulmicort Turbuhaler, is a corticosteroid with a high ratio of local to systemic effects that is administered to treat persistent asthma. The Turbuhaler achieves lung deposition approximately twice that of a metered-dose inhaler (MDI) with or without a spacer device. Budesonide inhalation powder has clinical efficacy equivalent to that of fluticasone and beclomethasone, but it has lower systemic bioavailability and fewer systemic side effects. As with other inhaled corticosteroids, dysphonia and oral candidiasis are the most frequent adverse effects, and systemic effects are infrequent. The initial starting dosage is 200 μg (1 puff) twice/day and may be increased to 800 μg twice/day in adults or 400 μg twice/day in children. Patients prefer the Turbuhaler to the MDI, Diskhaler, and Rotahaler because it is easier to use and more convenient to carry.     

Clinical Pharmacy Services in Hospitals Educating Pharmacy Students

In 1995 we conducted a national survey of 1102 acute care hospitals in the United States to determine types of clinical pharmacy services, patient-focused care, and pharmaceutical care used to educate and train pharmacy students, and compared outcomes with surveys in 1989 and 1992. Clinical pharmacy services offered in 50% or more of Pharm.D.-affiliated hospitals (core services) were drug-use evaluation, in-service education, pharmacokinetic consultations, adverse drug reaction management, drug therapy monitoring, protocol management (most common for aminoglycosides, nutrition, antibiotics, heparin, warfarin, theophylline), nutrition team, and drug counseling. Comprehensive pharmaceutical care programs were established in 64%, 42%, and 33% of Pharm.D., B.S., and nonteaching hospitals, respectively. Patient-focused care programs were beginning or established in 77%, 71%, and 60%, respectively. Pharmacists served as care team leaders in 23% of hospitals affiliated with a college of pharmacy. Most common ambulatory care clinics were oncology, anticoagulation, diabetes, geriatrics, refill, and infectious diseases/HIV. For-profit hospitals rarely provided education for pharmacy students. Thus patient-focused and comprehensive pharmaceutical care programs exist according to a hospital's academic program affiliation with Pharm.D. or B.S. degree program.     

Managing osteoarthritis pain when your patient fails simple analgesics and NSAIDs and is not a candidate for surgery

With no disease-modifying osteoarthritis drugs on the immediate horizon, the goal of osteoarthritis therapy remains management of pain and maintenance of function. Evidence supports use of nonpharmacologic measures including patient education, judicious exercise and weight loss, and assistive devices when appropriate to reduce pain and further loss of function. First line pharmacotherapy is acetaminophen or nonsteroidal anti-inflammatory drugs (NSAIDs). However, toxicities are associated with longterm use of these drugs. Evidence also supports the use of opioids in osteoarthritis pain management when other interventions are insufficient. NSAIDs and opioids are mutually dose sparing and combining relatively low doses of a drug from each class provides synergistic analgesia while limiting toxicity. Alternative therapies include tramadol and intra-articular injections of steroids and hyaluronic acid. There is evidence to support glucosamine as an adjunct in treating osteoarthritis. Evidence is lacking to support the use of chondroitin, S-adenosyl-methionine, or dimethyl sulfoxide in osteoarthritis pain management.     

Association between encounter frequency and time to blood pressure control among patients with newly diagnosed hypertension: a retrospective cohort study

This retrospective cohort study of 95 957 patients from a large integrated healthcare organization was conducted to examine whether the frequency and intervals between outpatient encounters were associated with achieving blood pressure (BP) control. Patients were followed up until they were censored or achieved BP control up to 1 year. Additionally, this study examined the time to BP control. On average, follow‐up was significantly longer in patients with uncontrolled BP at 292.9 days compared with 232.2 days in those with BP control. The controlled BP group had significantly more encounters on average compared with the uncontrolled BP group (4.1 vs 3.1, standardized difference 0.33). As the number of days increased between encounters from the 1 to < 14 days, there was a consistently lower likelihood of achieving BP control. Encounter intervals of ≥180 days were associated with the lowest likelihood of achieving BP control. These findings suggest that there may be an optimal number of encounters to benefit patients with hypertension.     

Premenstrual Asthma: The Effect of Estrogen on Symptoms,Pulmonary Function,and β2-Receptors

Study Objectives . To characterize asthma symptoms, pulmonary function, and responsiveness to β₂-agonist stimulation, and in vitro β₂-receptor density and cyclic adenosine 3′,5′-monophosphate (cAMP) response throughout the menstrual cycle in women with premenstrual asthma (PMA); and to examine the effect of exogenous estradiol administration on asthma symptoms, pulmonary function and responsiveness, and β₂-receptor density and function in these women. Design . Open-label, longitudinal, 9-week study. Setting . A university clinical research center. Patients . Seventeen women with mild to moderate asthma, of whom 14 completed the study. Interventions . Every morning on awakening during the entire 9-week study, each subject completed visual analog scales for asthma symptomatology (cough, wheezing, breathlessness, chest tightness) and measured and recorded her peak expiratory flow rate (PEFR) with a peak flow meter. Also measured at various times throughout the menstrual cycle were dyspnea index scores, pulmonary function (PEFR, forced expiratory volume in 1 sec [FEV₁]), pulmonary response to subcutaneous terbutaline, T lymphocyte β₂-receptor density (B_max) and function (cAMP), and estradiol, progesterone, and catecholamine concentrations, both with and without exogenous estradiol administration. Measurements and Main Results . At the time of enrollment, only 5 subjects reported premenstrual worsening of asthma symptoms, but all 14 had greater than 20% decrease in PEFR and/or increase in symptoms premenstrually during the study. Significant differences (p<0.05) existed in asthma symptoms and PEFR between day 13 (highest estradiol concentrations) and day 26 (lowest estradiol concentrations) of the menstrual cycle. Asthma symptoms and dyspnea index scores were significantly improved (p<0.05) after estradiol administration compared with baseline (premenstrual period without exogenous estrogen). Pulmonary response to terbutaline, β₂-receptor density and function, and catecholamine concentrations were not significantly altered after estradiol administration, but the trend was toward significant differences (0.05 < p < 0.2) in pulmonary function tests (PEFR, FEV₁). Conclusions . Even asthmatics not previously aware of PMA may experience premenstrual worsening of asthma symptoms and/or PEFR. Estradiol is associated with a significant improvement in asthma symptoms and dyspnea index scores. This ameliorating effect does not appear to be related to β₂-receptors.     

Relative Bioavailability of Ondansetron 8-mg Oral Tablets versus Two Extemporaneous 16-mg Suppositories: Formulation and Gender Differences

Study Objective . To compare the relative bioavailability of two 16-mg extemporaneously prepared suppository formulations with that of an 8-mg commercially available oral tablet. Design . Prospective, crossover bioavailability study. Setting . Inpatient clinical research center. Subjects . Sixteen young, nonsmoking, healthy volunteers. Interventions . Blood samples were obtained 24 and 48 hours after administration of an 8-mg oral ondansetron tablet and 16-mg suppository, respectively. Two 16-mg suppository formulations were compounded using commercially available Fattibase and Polybase. Measurements and Main Results . Ondansetron was well absorbed by both routes of administration. The following pharmacokinetic parameters (mean ± SEM) were obtained for the 8-mg tablet, 16-mg Fattibase suppository, and 16-mg Polybase suppository, respectively: area under the curve (AUC) in men 154.2 ± 21.77, 253.4 ± 72.3, 304.8 ± 62.2 ng·hr/ml; AUC in women 353.6 ± 32.7, 561.6 ± 103.6, and 768.7 ± 117.9 ng·hr/ml; maximum concentration (C_max) in men 45.5 ± 7.0, 40.6 ± 10.4, and 51.2 ± 6.7 ng/ml; C_max in women 51.4 ± 4.8, 47.1 ± 3.9, and 82.9 ± 6.6 ng/ml. Times to C_max (T_max; mean ± SEM) for men were 1.5 ± 0.3, 4.4 ± 0.5, and 2.9 ± 0.3 hours; T_max for women were 1.8 ± 0.3, 4.1 ± 0.4, and 4.4 ± 0.6 hours for the three formulations, respectively. Women had a consistently higher AUC for all three formulations than men (p < 0.05). Conclusion . With the exception of the 16-mg Polybase formulation in women, the two suppositories closely approximated the pharmacokinetics of the 8-mg oral tablet. These results suggest that gender may be a significant factor in ondansetron's disposition.