Extended stability of iobenguane under simulated clinical conditions.

PURPOSE: The stability of iobenguane sulfate stored at 4-7 degrees C over 91 days was studied. METHODS: An iobenguane sulfate solution at a concentration of 2.2 mg/mL was prepared in a top-fill i.v. bag using 143 mg of iobenguane sulfate and 65 mL of Sterile Water for Injection, USP. The solution was poured through a 0.22- microm filter assembly for sterilization into 60 1-mL polycarbonate plastic syringes. Each syringe was filled with 0.9 mL of the iobenguane sulfate solution and stored in amber plastic bags at 4-7 degrees C. The stability of iobenguane sulfate was analyzed using high-performance liquid chromatography immediately after solution preparation and on days 7, 14, 28, 42, 56, 70, and 91. Samples were inspected for chemical purity by observing for particulate formation and color change. RESULTS: The mean concentration of ioben-guane exceeded 93% of the initial concentration in all samples throughout the 91-day study period. No changes in color or turbidity were observed. CONCLUSION: Iobenguane sulfate 2.2 mg/mL was stable for 91 days when stored in polycarbonate syringes at 4-7 degrees C.     

Safety of intravenous bolus administration of gentamicin in pediatric patients.

OBJECTIVE: To determine the safety of gentamicin administered intravenously as a bolus. METHODS: All patients (n = 123, ages: up to 18y, 121; 21y, 1; 31y, 1) who received gentamicin intravenously as a bolus over a four-month period were studied retrospectively. Patient demographics, type of infection, dosing regimen, length of therapy, peak and trough serum concentrations, blood urea nitrogen, serum creatinine, and urine output were reviewed. Patients were stratified into four groups and data analyzed statistically. RESULTS: Mean initial dose (5.32 +/- 2.38 mg/kg/d) was consistent with established guidelines for age and kidney development, with subsequent adjustments based on serum concentrations. Susceptible organisms were eradicated with a mean length of therapy of 6.9 +/- 6.9 days (range 1-35). Patients received a median of nine doses: 42% received doses every eight hours and 33% received doses every 24 hours. No relationship between dosing and abnormal serum creatinine were found (p = 0.69). The estimated cost savings mainly from less nursing time and lower equipment and supply use were $50/patient with bolus administration of gentamicin. CONCLUSIONS: Intravenous bolus administration was safe in pediatric patients and was associated with lower costs.     

Accuracy of delivery of cefazolin, chloramphenicol, and vancomycin by a controlled-release membrane infusion device

The effects of flow rate and drug concentration on the accuracy of in vitro delivery of cefazolin, chloramphenicol, and vancomycin by a new controlled-release membrane infusion device, MICROS, were studied. Cefazolin, chloramphenicol, and vancomycin 1 g in sterile water for injection 10 mL were injected into the drug chamber of the device and delivered through an administration set with 0.9% sodium chloride injection from a primary line. Drug delivery was studied at four flow rates (0.5, 1.0, 1.5, and 2.0 mL/min). In addition, three concentrations of each drug (25, 50, and 100 mg/mL for cefazolin and vancomycin, and 50, 100, and 200 mg/mL for chloramphenicol) were studied at a fixed flow rate of 1 mL/min. Samples were collected in triplicate every 2.5-5.0 minutes using a fraction collector over a 90-minute period for cefazolin and a 120-minute period for chloramphenicol and vancomycin. The concentration of each drug was measured by high-performance liquid chromatography. At various flow rates, the time for delivery of greater than or equal to 95% of each dose ranged from 30 to 55 minutes for cefazolin, 45 to 70 minutes for chloramphenicol, and 50 to 65 minutes for vancomycin. At various concentrations, greater than or equal to 95% of each dose was delivered in 40 to 55 minutes for cefazolin, 40 to 70 minutes for chloramphenicol, and 50 to 60 minutes for vancomycin. The desired delivery times were 30-60 minutes for cefazolin and chloramphenicol and 50-70 minutes for vancomycin. Delivery of cefazolin and vancomycin by the MICROS membrane infusion system was accurate. Some delay was encountered in the delivery of chloramphenicol.(ABSTRACT TRUNCATED AT 250 WORDS)     

Stability of lorazepam diluted in bacteriostatic water for injection at two temperatures

Lorazepam is commonly used to produce sedation in infants. As errors may occur with the measurement of small volumes of concentrated drugs, we studied the stability of lorazepam diluted from 4 mg/ml to 1 mg/ml in bacteriostatic water for injection at two temperatures. The diluted lorazepam was stored in 10 glass vials (five at 22°C and five at 4°C). Samples were collected at 0, 7, 14, 28, 42, 56, 70 and 91 days after storage at each temperature. Lorazepam was measured in duplicate from each of five vials (n = 10) at each temperature by a specific and stability–indicating high–performance liquid chromatographic (HPLC) method. After 7 days' storage, the mean lorazepam concentration was 88% of the original concentration at 22°C, and 90% of the original concentration at 4°C. After 2 weeks of storage, the mean lorazepam concentration was 42% of the original concentration at 22°C, and 15% of the original concentration at 4°C. Crystals appeared after 4 weeks of storage at 22°C and after 2 weeks of storage at 4°C. At 3 months the mean lorazepam concentration was 6–1% and 7–5% of the original concentration at 22°C and 4°C, respectively. Thus, lorazepam diluted in bacteriostatic water for injection and stored in glass vials is stable for less than 7 days at 22°C and for 7 days at 4°C.     

Pharmacokinetics of loracarbef in pediatric patients.

Loracarbef is an investigational oral antibiotic but its pharmacokinetics have not been studied after multiple oral doses in pediatric patients. The pharmacokinetics of loracarbef were determined in 18 pediatric patients after multiple oral doses. 8 patients with streptococcal pharyngitis received 7.5 mg/kg every 12 h, and 10 patients with otitis media were given 15 mg per kg every 12h. Multiple blood and urine samples were collected to measure loracarbef concentrations. In patients with streptococcal pharyngitis, the mean maximum serum concentration (Cmax), the time to achieve maximum concentration (Tmax), area under the serum concentration-time curve (AUC) and elimination half-life (t1/2) were 10.6 +/- 3.6 mcg/ml, 0.78 +/- 0.21 h, 21.4 +/- 7.2 mcg.h/ml, and 1.2 + 0.4 h, respectively. The mean Cmax, Tmax, AUC and t1/2 were 18.0 +/- 5.4 mcg/ml, 0.83 +/- 0.44 h, 35.6 +/- 9.4 mcg.h/ml, and 1.1 +/- 0.5 h, respectively, in patients with otitis media. The Cmax exceeded the minimum inhibitory concentration of common susceptible pathogens causing pharyngitis and otitis media by severalfold. Nearly 60% of the dose was excreted unchanged in the urine during the dosage interval. The pharmacokinetics were independent of dose. Loracarbef was well tolerated in all patients. These data suggest that loracarbef may be used safely at doses of 7.5 mg/kg every 12 h in pediatric patients with streptococcal pharyngitis and 15 mg/kg every 12 h in those with otitis media.     

Sulbactam/ampicillin, a new beta-lactamase inhibitor/beta-lactam antibiotic combination

Sulbactam/ampicillin is a combination of a beta-lactamase inhibitor with minimal intrinsic antibacterial activity (sulbactam sodium), and an aminopenicillin (ampicillin sodium). The addition of sulbactam to ampicillin has no effect on the chemical stability of ampicillin in aqueous solution, and the administration guidelines of the combination are the same as for ampicillin alone. Sulbactam acts primarily by irreversible inactivation of beta-lactamases from most beta-lactamase-producing organisms. The pharmacokinetics of sulbactam are similar to those of ampicillin with an elimination half-life of about one hour in most patients. One difference is that serum and tissue concentrations of sulbactam are usually twice those of ampicillin, at equivalent doses. The sulbactam/ampicillin combination has been approved for the treatment of adults with intraabdominal, skin and skin structure, and gynecological infections due to beta-lactamase-producing bacteria such as Staphylococcus aureus, Escherichia coli, and species of Klebsiella and Bacteroides. Clinical studies to date have also shown the combination to be effective for the treatment of meningitis, pneumonia, gonorrhea, epiglottis, urinary tract infections, cervical adenitis, and as prophylaxis for abdominal and gynecological surgeries. Many of these studies, however, have included small numbers of patients and/or had design flaws. Adverse effects have been minor with most being attributed to the ampicillin component. Sulbactam/ampicillin compares favorably with other antibiotic regimens in terms of acquisition costs and ease of administration.     

Effect of primary fluids and dilutional volumes on the delivery of cefazolin sodium by a membrane infusion device

The influence of primary fluids and dilutional volumes on the accuracy of in vitro delivery of cefazolin sodium by gravity flow through a new controlled-release membrane infusion device was studied. For primary fluid studies, cefazolin 1 g (as the sodium salt) in 10 mL of sterile water for injection was injected into the drug chamber, which is separated by a membrane from the fluid chamber; the entire dose passes into the fluid chamber over a set time. The inlet port of the fluid chamber was connected to the 1-L primary fluid bag, and the outlet port was connected to an administration set. The primary fluids included 0.9% sodium chloride injection; 5% dextrose injection; 10% dextrose injection; 5% dextrose and 0.45% sodium chloride injection; 5% dextrose, 0.45% sodium chloride, and potassium chloride 20 meq/L injection; and 2.2% amino acids with electrolytes in 25% dextrose injection. For dilutional volume studies, cefazolin sodium 1 g diluted in 5, 10, and 15 mL of sterile water for injection was infused with 0.9% sodium chloride injection. The flow rate was set at 1 mL/min. Serial samples were collected in triplicate every five minutes over a 90-minute period and analyzed by high-performance liquid chromatography. The time needed to deliver more than 95% of the cefazolin doses ranged from 35 to 50 minutes using various primary fluids and from 35 to 55 minutes using various dilutional volumes. The manufacturer recommends that a cefazolin dose be delivered completely within 30-60 minutes. The solutes in the primary fluids and the volume injected did not appear to affect the delivery of cefazolin by a controlled-release membrane device.     

Dopamine and dobutamine in pediatric therapy

Dopamine hydrochloride is widely used to increase blood pressure, cardiac output, urine output, and peripheral perfusion in neonates, infants, and older children with shock and cardiac failure. Its pharmacologic effects are dose dependent, and at low, intermediate, and high dosages include dilation of renal, mesenteric, and cerebral vasculature; inotropic response in the myocardium; and increases in peripheral and renal vascular resistance, respectively. The inotropic response is diminished in neonates compared with older children and adults due to maturational differences in norepinephrine stores. The clearance of dopamine varies widely in the pediatric population, depending on age. Its elimination half-life is approximately 2 minutes in full-term neonates and older children, and may be as long as 4-5 minutes in preterm infants. Due to immaturity of the autonomic nervous system, the drug may produce some adverse respiratory responses at high dose in neonates, the most common being tachycardia and cardiac arrhythmias. Dobutamine resembles dopamine chemically and is an analog of isoproterenol. It is relatively cardioselective at dosages used in clinical practice, with its main action being on beta 1-adrenergic receptors. Unlike dopamine, it does not have any effect on specific dopaminergic receptors. Dobutamine is used to increase cardiac output in infants and children with circulatory failure. Its elimination half-life is about 2 minutes in adults and older children. No information is available about its pharmacokinetics in neonates and infants. Adverse effects such as an increase in heart rate usually occur at high dosages.