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Biomedical subjects

A Chin

Publications and source records attributed to A Chin.

At least 37 records · Page 2Linked to original sources

Stability of granisetron hydrochloride in a disposable elastomeric infusion device.

The stability and sterility of granisetron hydrochloride in 5% dextrose injection or 0.9% sodium chloride injection when stored in a disposable elastomeric infusion device were studied. Granisetron was diluted to 0.02 mg/mL (as the hydrochloride salt) in 5% dextrose chloride injection. The solution was placed in the drug reservoir of a disposable elastomeric infusion device and refrigerated at 4 degrees C for 14 days. A total of eight pumps were prepared, four containing granisetron 0.02 mg/mL in 5% dextrose injection and four containing granisetron 0.02 mg/mL in 0.9% sodium chloride injection. The solutions were assayed for granisetron concentration by stability-indicating high-performance liquid chromatography at 0 hours, 24 hours, 48 hours, 7 days, and 14 days. Each solution was inspected for clarity, color, and precipitation, and sterility testing was performed. Throughout the study, the mean concentration of granisetron remaining was more than 92% of the initial concentration both in 5% dextrose injection and in 0.9% sodium chloride injection. Individual solutions in 0.9% sodium chloride injection consistently maintained more than 90% of the initial drug concentration for only seven days. No microbial growth was detected. No precipitation, color change, or haziness was seen. Granisetron 0.02 mg/mL (as the hydrochloride salt) was stable and free of microbial growth in 0.9% sodium chloride injection for up to 7 days and stable and free of microbial growth in 5% dextrose injection for up to 14 days when stored at 4 degrees C in a disposable elastomeric infusion device.

Antiemetics↗

Stability of piperacillin sodium-tazobactam sodium and ranitidine hydrochloride in 0.9% sodium chloride injection during simulated Y-site administration.

The stability of piperacillin sodium plus tazobactam sodium and ranitidine hydrochloride in 0.9% sodium chloride injection during simulated Y-site administration was studied. Triplicate test solutions of piperacillin 40 mg/mL plus tazobactam 5 mg/mL (as the sodium salts) or piperacillin 80 mg/mL plus tazobactam 10 mg/mL (as the sodium salts) were mixed 1:1 with ranitidine 0.5 and 2.0 mg/mL (as the hydrochloride salt). The solutions were stored at 23 degrees C, and samples were removed at zero, one, two, and four hours for measurement of drug concentration by stability-indicating high-performance liquid chromatography. At the time of sampling and before any dilution, each sample was visually inspected for color and precipitation, and pH was determined. At all sampling times, the concentrations of piperacillin, tazobactam, and ranitidine were > 90% of initial concentrations. There were no substantial changes in pH or color. Tazobactam 5 mg/mL (as the sodium salt) and ranitidine 0.5 and 2 mg/mL (as the hydrochloride salt) in 0.9% sodium chloride injection were stable for up to four hours during simulated Y-site administration. Piperacillin 80 mg/mL plus tazobactam 10 mg/mL (as the sodium salts) and ranitidine 0.5 and 2 mg/mL (as the hydrochloride salt) were stable for up to four hours during simulated Y-site administration.

Chromatography, High Pressure Liquid↗

Stability of paclitaxel with ondansetron hydrochloride or ranitidine hydrochloride during simulated Y-site administration.

The stability of paclitaxel with either ondansetron hydrochloride or ranitidine hydrochloride during simulated Y-site injection at room temperature was studied. Triplicate test solutions of paclitaxel 0.3 and 1.2 mg/mL were admixed 1:1 with ondansetron 0.03 and 0.3 mg/mL (as the hydrochloride salt) or ranitidine 0.5 and 2.0 mg/mL (as the hydrochloride salt). Also, paclitaxel 1.2 mg/mL was admixed 1:1:1 with ondansetron 0.3 mg/mL and ranitidine 2.0 mg/mL. The solutions were stored in glass containers at room temperature, and samples were removed at zero, one, two, and four hours for immediate assay. At the time of the assay and before any dilution, each sample was visually inspected for clarity, color, and precipitation, and the pH was determined. Drug concentrations were measured by stability-indicating high-performance liquid chromatographic procedures. Throughout the study, more than 90% of the initial concentrations of paclitaxel, ondansetron, and ranitidine remained in the solutions. No precipitates, color changes, or haziness was seen. The changes in pH were minor. Paclitaxel in concentrations of 0.3 and 1.2 mg/mL was stable when mixed with either ondansetron (0.03 or 0.3 mg/mL, as the hydrochloride salt) or ranitidine (0.5 or 2.0 mg/mL, as the hydrochloride salt) and stored in glass containers for four hours. Paclitaxel 1.2 mg/mL was also stable when mixed with both ondansetron 0.3 mg/mL and ranitidine 2.0 mg/mL and stored in glass containers for four hours.

Chromatography, High Pressure Liquid↗

Cefepime: a new fourth-generation cephalosporin.

The chemistry, pharmacology, antimicrobial spectrum, pharmacokinetics, clinical efficacy, adverse effects, and dosage of cefepime are reviewed. Fourth-generation cephalosporins, such as cefepime, have a quaternary nitrogen that is positively charged at the 3-position, providing the properties of a zwitterion. A 2-aminothiazolyl-acetamido group in the side chain at the 7-position with an alpha-oxyimino substitution may enhance stability against beta-lactamases by preventing the enzymes' approach to the main nucleus. Cefepime may exert its antimicrobial effect by attaching to specific penicillin-binding proteins, disrupting cell-wall synthesis. Cefepime has good activity against gram-positive organisms, such as Staphylococcus aureus, and gram-negative organisms, such as Pseudomonas aeruginosa. Cefepime is not active in vitro against Enterococcus faecalis, Clostridium difficile, and methicillin- and cefazolin-resistant Staph. aureus. Cefepime's activity against gram-negative organisms is similar to that of most third-generation cephalosporins. The agent has poor activity against Bacteroides species. The most common mechanism of resistance to cefepime is the excess production of beta-lactamases. Maximum peak plasma concentrations are two to three times higher after i.v. administration than after intramuscular administration. In healthy adults, the volume of distribution is 13-22 L and the elimination half-life is 2-2.3 hours. Clinical studies show that cefepime is as effective as cefotaxime or ceftazidime in patients with infections of the lower respiratory tract, skin and skin structures, urinary tract, or female reproductive system. Cefepime reduces fever as effectively as ceftazidime or piperacillin plus gentamicin in neutropenic patients. The most common adverse effects of cefepime are headache (2.4%), nausea (1.8%), rash (1.8%), and diarrhea (1.7%). Depending on creatinine clearance, the dosage of cefepime is 1000-2000 mg i.v. every 8-24 hours for life-threatening infections and 500-2000 mg i.v. every 12-24 hours for severe infections. Cefepime's clinical efficacy is comparable to that of ceftazidime and cefotaxime.

Animals↗

Paclitaxel stability and compatibility in polyolefin containers.

OBJECTIVE: To determine the compatibility and stability of paclitaxel in polyolefin containers. DESIGN: The following paclitaxel concentrations were determined by a stability-indicating HPLC method: 0.3 and 1.2 mg/mL diluted in dextrose 5% for injection, USP (D5W) or sodium chloride 0.9% for injection, USP (NS). The solutions were prepared in polyolefin containers and the stability and compatibility were monitored for 48 hours when stored at ambient temperature (20-23 degrees C) and normal fluorescent lighting. A mixture of the drug carrier consisting of approximately 10% polyoxyethylated castor oil (Cremophor EL) and 10% ethanol in D5W and NS, without paclitaxel, was studied to differentiate the effect of paclitaxel from the effect of the drug carrier on the container. Paclitaxel concentrations, pH changes, and visual clarity were used as stability and compatibility indicators. RESULTS: Paclitaxel concentrations remained at 96-99 percent of the initial concentration for up to 48 hours when placed in the polyolefin containers. No changes in color or visual clarity were noted. Only minor changes in the pH of the admixtures were observed. CONCLUSIONS: Paclitaxel diluted in D5W or NS at concentrations of 0.3 and 1.2 mg/mL is stable and compatible in flexible, polyolefin containers for up to 48 hours.

Drug Packaging↗

Effect of antihypertensive formulation on health service expenditures.

A major barrier to the management of hypertension is the extent to which patients comply with the treatment regimen. Herein we report the findings of a retrospective analysis designed to discern the relationship between antihypertensive formulation, regimen compliance and the utilization of health care services. Data for this analysis were derived from the state of South Carolina's Medicaid computer archive. The study population consisted of 1,000 randomly selected beneficiaries initially prescribed one of the following antihypertensive regimens as monotherapy: atenolol (daily); captopril (twice daily); oral clonidine (twice daily); transdermal clonidine (once a week); diltiazem (twice daily); enalapril (twice daily); metoprolol (twice daily); prazosin (twice daily); terazosin (daily); and verapamil-SR (daily). Multivariate regression analysis was used to determine the incremental influence of selected demographic characteristics, utilization of medical services prior to diagnosis for hypertension, initial antihypertensive medication, medication possession ratio for antihypertensive therapy, and the number of maintenance medications for disease state processes other than hypertension on post-period health care expenditure. Results indicate that patients initially prescribed antihypertensive medication requiring daily or weekly administration experience infrequent changes in their therapeutic regimen, far less use of concomitant therapy for blood pressure control, an increased utilization of antihypertensive medication, and a decrease in the use and cost of physician, hospital and laboratory services.

Aged↗

A cluster of coagulase-negative staphylococcal bacteremias associated with peripheral vascular catheter colonization in a neonatal intensive care unit.

BACKGROUND: A cluster of six neonatal cases of coagulase-negative staphylococcal bacteremias occurred in a Los Angeles County neonatal intensive care unit in March 1989. METHODS: A retrospective cohort study assessed the impact of host-and delivery-related variables, length of hospitalization, duration of antibiotic treatment, performance or duration of invasive procedures, and staffing variables on risk of coagulase-negative staphylococcal bacteremia. RESULTS: Unstratified analyses yielded eight risk factors with risk ratios greater than 2. After stratification by gestational age (less than 29 weeks) and low birth weight (less than 1500 gm), frequency of blood transfusions, duration of respiratory therapy, heparin lock and central vascular line placement, and hyperalimentation remained associated with elevated risk. Two species were identified, arguing against a common source of infection. Of four cohort months with more than 15 very low birth weight infants in the neonatal intensive care unit, an elevation of coagulase-negative staphylococcus-positive blood cultures and diagnosed bacteremias occurred in only two. CONCLUSIONS: This cluster of coagulase-negative staphylococcal bacteremia was probably caused by frequent manipulation of catheters in neonates who were at heightened risk because of low birth weight and prematurity.

Bacteremia↗

Cefepime clinical pharmacokinetics.

Cefepime is a new parenteral cephalosporin with antimicrobial activity similar to third-generation cephalosporins. It acts against the Enterobacteriaceae family, and Pseudomonas aeruginosa, but maintains Gram-positive activity similar to that of first- or second-generation cephalosporins. Cefepime has in vitro activity against many bacterial isolates resistant to ceftazidime and cefotaxime, is stable against chromosomally mediated beta-lactamases, demonstrates lower affinity for these enzymes and shows a high resistance to enzymatic hydrolysis. Clinical uses thus far include treatment of lower respiratory tract, intra-abdominal and urinary tract infections, skin and soft tissue infections and for prophylaxis in biliary tract and prostate surgery. Pharmacokinetic studies indicate that cefepime exhibits linear pharmacokinetic behaviour. Pharmacokinetic variables are not significantly different between single- and multiple-dose administration, indicating a lack of drug accumulation in patients with normal renal function. Cefepime is not highly bound to plasma proteins, with binding values of approximately 16 to 19%. The drug is widely distributed in various biological tissues and fluids. The primary route of elimination is from the kidneys, with over 80% of the drug recovered in the urine as unchanged drug in patients with normal renal function. Total drug clearance and renal clearance are similar to creatinine clearance, and glomerular filtration is thought to be the primary mechanism of renal excretion. The elimination half-life is approximately 2 to 2.5 h in patients. Cefepime is removed by haemodialysis (over 3h) and peritoneal dialysis (over 72h) to an appreciable extent, with 40 to 68% and 26% of the drug removed, respectively. Overall, cefepime is well tolerated by patients and no significant drug interactions have been reported to date.

Bacteria↗

Prospective randomized study of two different doses of clindamycin admixed with gentamicin in the management of perforated appendicitis.

Septic complications after surgery for enterogenous peritonitis are minimized by adjuvant antibiotics effective against aerobes and anaerobes. Historically, "gold standard" therapy included an aminoglycoside plus clindamycin, the latter given at 600 mg intravenous piggyback (IVPB), every 6 hours. Clindamycin pharmacokinetics suggests that it can be given q8h and admixed with gentamicin, thereby markedly reducing the cost of administration. Although this is now common practice, there is no prospective study comparing the efficacy of the two dose schedules in peritonitis. This study was designed to test the hypothesis regarding the clinical efficacy of the two regimens. One hundred twenty-six patients with gangrenous (n = 34) or perforated appendicitis (n = 91) were randomized (2:1) to receive gentamicin admixed with clindamycin 900 mg IVPB every 8 hours (Group I n = 80) or gentamicin IVPB q8h plus clindamycin 600 mg IVPB every 6 hours (Group II n = 46). Appendectomy was performed, and aerobic and anaerobic cultures were obtained. Twenty-one patients had simultaneous determinations of clindamycin levels in plasma, peritoneal fluid, and appendix. Outcome analysis revealed no significant differences in postoperative days of fever, days non per os, antibiotic therapy, or hospitalization. There were 6 failures (4 abscesses and 2 wound infections) in Group I and 4 failures (1 abscess and 3 wound infections) in Group II. Both antibiotic regimens provided clinically equivalent results in mixed infections due to aerobic and anaerobic bacteria. The admixed clindamycin, administered every 8 hours, results in at least 20% reduction in costs. This is an important consideration.

Adult↗

Pharmacokinetic population parameters for aminoglycosides in cholecystitis patients.

We report the use of a new method to determine patient population pharmacokinetic parameters (nonparametric expected maximum or NPEM). Our purpose was to develop and then analyze the utility of these parameters, compared to a more traditional approach. Nineteen patients with acute cholecystitis made up the control group for defining the parameters via NPEM. The standard of practice was to use a model created from a different intraabdominal infection group (appendicitis), referred to as "surgical patient model." These two models were compared with a group of 23 patients receiving gentamicin for acute cholecystitis. We concluded that the NPEM model was superior to the surgical patient model in predicting gentamicin trough and peak levels with less bias and better precision.

Adult↗

Tissue concentrations of cefepime in acute cholecystitis patients.

Cefepime is a new broad-spectrum cephalosporin with activity against Staphylococcus, Streptococcus, Pseudomonas, and the Enterobacteriaceae. The purpose of this study was to measure cefepime concentrations in plasma, peritoneal fluid, bile fluid and appendix tissue in patients undergoing elective cholecystectomy. Patients were randomly assigned to receive either cefepime, 2 g intravenously in phosphate buffer (IVPB) q 12 h or gentamicin 1.5 mg/kg IVPB q 8 h plus mezlocillin 4 g IVPB q 6 h. During surgery, gall bladder tissue, plasma, peritoneal fluid, and bile fluid samples were obtained at approximately the same time. Thirty-three patients had data acceptable for analysis. Values are given as mean +/- standard deviation. The mean delta time (defined as the time between the administration of cefepime and the time the samples were obtained) was 8.58 +/- 3.53 h. The values for plasma, peritoneal fluid, bile fluid, and gall bladder tissue concentrations were 7.63 +/- 14.17 micrograms/ml, 5.66 +/- 6.80 micrograms/ml, 15.51 +/- 16.94 micrograms/ml, and 5.36 +/- 6.57 micrograms/gm, respectively. The peritoneal fluid/plasma ratio was 2.10 +/- 2.33, the bile fluid/plasma ratio was 14.44 +/- 31.99, and the gall bladder tissue/plasma ratio was 1.44 +/- 1.82. There was a significant correlation between peritoneal fluid and plasma concentration (r = 0.91, p less than 0.0005), and gall bladder tissue and plasma concentration (r = 0.90, p less than 0.0005). There was no correlation between bile fluid and plasma cefepime concentrations. The minimum inhibitory concentration (MIC) data from previous in vitro studies indicate that cefepime concentrations achieved in this patient population would be adequate against typical biliary tract pathogens.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗