Pharmacokinetics of cefpirome in pediatric patients.

Cefpirome is a new investigational cephalosporin. We designed a study to determine the pharmacokinetics and tolerance of cefpirome in pediatric patients. A single dose of cefpirome was administered intravenously over 15 min to 18 patients (age 0.5 to 18 years). The doses were 10 mg/kg of body weight for five patients, 25 mg/kg of body weight for seven patients, and 50 mg/kg of body weight for six patients. Blood samples were collected at 0, 0.25, 0.5, 1, 3, 5, and 8 h after the dose, and cefpirome was measured by a high-performance liquid chromatography method. The maximum concentration in serum ranged from about 53.6 to 454 micrograms/ml after doses of 10 to 50 mg/kg. The total body clearance, apparent volume of distribution, and elimination half-life were 2.15 +/- 0.70 ml/min/kg, 0.32 +/- 0.32 liter/kg, and 1.8 +/- 1.3 h, respectively. No significant adverse effects were attributed to cefpirome. These data may be useful in conducting efficacy and safety studies of cefpirome in pediatric patients.     

Cefadroxil kinetics and dynamics in a pediatric patient with acute osteomyelitis

Cefadroxil has been used for the treatment of acute osteomyelitis. However, its pharmacokinetics and pharmacodynamics have not been studied in these patients. We evaluated the kinetics and dynamics of cefadroxil in a pediatric patient with osteomyelitis caused by Staphylococcus aureus. After initial clinical improvement on intravenous nafcillin, the patient received oral cefadroxil, 60 mg/kg every 12 h. Blood samples were collected at 0, 1, 2, 4, 6, 8 and 12 h; bactericidal titers were determined at 2 and 12 h. Cefadroxil was measured by an HPLC method. The peak and trough serum concentration of cefadroxil was 35.4 and 0.5 micrograms/ml, respectively. The oral clearance and elimination half-life were 11.5 ml/min/kg and 2.4 h, respectively. The peak bactericidal titer was 1:4 and the trough titer was less than 1:2 for the infecting organism. The child's finger appeared worse with an increase in swelling and erythema after 2 days of cefadroxil therapy. Cefadroxil was discontinued and the patient was treated successfully with intravenous nafcillin. The apparent failure of cefadroxil therapy can be explained by lower than recommended peak (greater than or equal to 1:8) and trough (greater than or equal to 1:2) titers for therapeutic success. Thus, an alternative dosage regimen of cefadroxil should be considered in the future studies.     

Residency requirement for pharmacists providing direct patient care

A residency requirement has been proposed as a prerequisite for all pharmacists providing direct patient care. This editorial explores the basis for requiring a residency, direct patient care offered by pharmacists with or without a residency, needs to increase interprofessional team-based health care, importance of distinguishing levels of pharmacy practice, role of pharmacy technicians, availability of residency positions, and future of pharmacy residencies. All PharmD graduates should be able to provide a certain level of direct patient care, including medication therapy management services, without completing a residency, and residency programs should be offered for complex levels of direct patient care in all practice settings.     

Decreased motility of the lower esophageal sphincter in a rat model of gastroesophageal reflux disease may be mediated by reductions of serotonin and acetylcholine signaling

To elucidate the altered function of the lower esophageal sphincter (LES) in gastroesophageal reflux disease (GERD), we evaluated the motility proximal to LES using force transducers, contraction and relaxation responses to neurotransmitters in LES strips, and gene expression of neurotransmitter receptors in GERD rats. Force transducers were applied to the proximal LES, and contraction of the LES was monitored during free moving. In addition, LES was isolated from sham-operated and GERD rats to investigate the LES function in an organ bath, and to determine gene expression. The in vivo motility proximal to LES (% motility index) in conscious rats was decreased by atropine treatment and increased by cisapride (5-HT(4) receptor agonist) treatment. Acetylcholine- and serotonin (5-HT)-induced LES contraction and sodium nitroprusside-induced relaxation in LES strips of GERD rats markedly decreased compared to sham-operated rats. The mRNA expressions of 5-HT(4) and muscarinic acetylcholine 3 receptors were significantly reduced in esophageal LES strips of GERD rats compared with sham-operated rats. Intraperitoneal administration of cisapride improves the erosive damage in the esophagus in GERD rats. It is suggested that the reduction of 5-HT-induced contraction in LES strips in GERD rats may be partly due to the decrease in 5-HT(4)-receptor activation. The reduction of LES function may be due to the decrease in neurotransmitters signal transduction, leading to the deterioration of histopathological damage in GERD.     

Potentially Inappropriately Prescribed Medications Among Medicare Medication Therapy Management Eligible Patients with Chronic Kidney Disease: an Observational Analysis

BackgroundPotentially inappropriately prescribed medications (PIPMs) among patients with chronic kidney disease (CKD) may vary among clinical settings. Rates of PIPM are unknown among Medicare-enrolled Medication Therapy Management (MTM) eligible patients.ObjectivesDetermine prevalence of PIPM among patients with CKD and evaluate characteristics of patients and providers associated with PIPM.DesignAn observational cross-sectional investigation of a Medicare insurance plan for the year 2018.PatientsMedicare-enrolled MTM eligible patients with stage 3–5 CKD.Main MeasuresPIPM was identified utilizing a tertiary database. Logistic regression assessed relationship between patient characteristics and PIPM.Key ResultsInvestigation included 3624 CKD patients: 2856 (79%), 548 (15%), and 220 (6%) patients with stage 3, 4, and 5 CKD, respectively. Among patients with stage 3, stage 4, and stage 5 CKD, 618, 430, and 151 were with at least one PIPM, respectively. Logistic regression revealed patients with stage 4 or 5 CKD had 7–14 times the odds of having a PIPM in comparison to patients with stage 3 disease (p < 0.001). Regression also found PIPM was associated with increasing number of years qualified for MTM (odds ratio (OR) 1.46–1.74, p ≤ 0.005), female gender (OR 1.25, p = 0.008), and increasing polypharmacy (OR 1.30–1.57, p ≤ 0.01). Approximately 14% of all medications (2879/21093) were considered PIPM. Majority of PIPMs (62%) were prescribed by physician primary care providers (PCPs). Medications with the greatest percentage of PIPM were spironolactone, canagliflozin, sitagliptin, levetiracetam, alendronate, pregabalin, pravastatin, fenofibrate, metformin, gabapentin, famotidine, celecoxib, naproxen, meloxicam, rosuvastatin, diclofenac, and ibuprofen.ConclusionOver one-third of Medicare MTM eligible patients with CKD presented with at least one PIPM. Worsening renal function, length of MTM eligibility, female gender, and polypharmacy were associated with having PIPM. Majority of PIPMs were prescribed by PCPs. Clinical decision support tools may be considered to potentially reduce PIPM among Medicare MTM–enrolled patients with CKD.Supplementary InformationThe online version contains supplementary material available at 10.1007/s11606-020-06537-z.KEY WORDS: Medicare, chronic kidney disease, medication therapy management, older adult     

Treatment of irritable bowel syndrome

What is known and Objective: The complexity and diversity of irritable bowel syndrome’s (IBS) presentation make treatment difficult. Although there are reviews and guidelines for treating IBS, they focus on the efficacy of medications for IBS symptoms using high‐priority endpoints, leaving those of lower priority largely unreported. Therefore, the aim of this review is to provide a comprehensive evidence‐based review of the efficacy of medications to treat IBS symptoms, reported by IBS subtype, including secondary symptom endpoints that are often underreported. Methods: A review of PubMed for articles published through December 2009 using the keywords: ‘irritable bowel syndrome’, ‘therapeutics’, ‘antidiarrhoeals’, ‘laxatives’, ‘loperamide’, ‘dietary fibre’, ‘psyllium’, ‘calcium polycarbophil’, ‘bulking agents’, ‘lubiprostone’, ‘antidepressant agents, tricyclics’ and its representative entities, ‘serotonin reuptake inhibitors’ and its representative entities, ‘dicyclomine’, hyoscyamine’, ‘peppermint oil’, ‘parasympatholytics’ and its representative entities, ‘rifaximin’, ‘pregabalin’, ‘gabapentin’, ‘clonidine’, ‘octreotide’, ‘atropine’ and ‘probiotics’ is provided. Placebo‐controlled trials were evaluated for the strength of evidence supporting the efficacy of each medication for explicit IBS symptoms. The efficacy of each medication for the symptoms of abdominal pain, bloating, stool form, mucus, urgency, feeling of incomplete evacuation, flatulence, frequency, or borborgymi and overall symptoms are reported by IBS subtype. Results and Discussion: The literature search identified 58 placebo‐controlled trials of the efficacy of medications for treating IBS symptoms, which were critically evaluated and reported. The available studies suggest improvement in various IBS symptoms with loperamide, fibre supplements, lubiprostone, tricyclic antidepressants (TCAs), selective serotonin receptor inhibitors (SSRIs), antispasmotics, rifaximin, pregabalin, gabapentin, clonidine, octreotide and probiotic treatments. What is new and Conclusion: This review is the first to compile the available evidence on the efficacy of the various pharmacological treatments for IBS on the basis of IBS subtype and specific symptoms. This evidence is limited and more well‐designed studies are required to better inform therapeutic decision‐making in the management of this difficult syndrome.     

Optimization of formulation variables for the development of long acting microsphere based depot injection of olanzapine

This work was aimed to optimize the composition of microspheres of olanzapine to design long acting depot injection for the treatment of psychosis. Solvent evaporation method was used for the fabrication of microspheres. Different formulation variables for the solvent evaporation method, viz., effect of theoretical drug loading, type of surfactant and its concentration, temperature, volume of external phase and presence of salt in external aqueous phase, conditions and time of solvent evaporation and drying methodology were optimized. The microspheres were characterized for encapsulation efficiency, particle size, surface morphology, residual solvent content, drug release profile and drug release kinetics. The optimized formulation showed consistent drug release for upto 14 days time period.