Single-dose pharmacokinetics of a pleconaril (VP63843) oral solution in children and adolescents. Pediatric Pharmacology Research Unit Network.
Pleconaril is an orally active, broad-spectrum antipicornaviral agent which demonstrates excellent penetration into the central nervous system, liver, and nasal epithelium. In view of the potential pediatric use of pleconaril, we conducted a single-dose, open-label study to characterize the pharmacokinetics of this antiviral agent in pediatric patients. Following an 8- to 10-h period of fasting, 18 children ranging in age from 2 to 12 years (7.5 +/- 3.1 years) received a single 5-mg/kg of body weight oral dose of pleconaril solution administered with a breakfast of age-appropriate composition. Repeated blood samples (n = 10) were obtained over 24 h postdose, and pleconaril was quantified from plasma by gas chromatography. Plasma drug concentration-time data for each subject were fitted to the curve by using a nonlinear, weighted (weight = 1/Ycalc) least-squares algorithm, and model-dependent pharmacokinetic parameters were determined from the polyexponential parameter estimates. Pleconaril was well tolerated by all subjects. A one-compartment open-model with first-order absorption best described the plasma pleconaril concentration-time profile in 13 of the subjects over a 24-h postdose period. Pleconaril pharmacokinetic parameters (means +/- standard deviations) for these 13 patients were as follows. The maximum concentration of the drug in serum (Cmax) was 1,272.5 +/- 622.1 ng/ml. The time to Cmax was 4.1 +/- 1.5 h, and the lag time was 0.75 +/- 0.56 h. The apparent absorption rate constant was 0.75 +/- 0.48 1/h, and the elimination rate constant was 0.16 +/- 0.07 1/h. The area under the concentration-time curve from 0 to 24 h was 8,131.15 +/- 3,411.82 ng.h/ml. The apparent total plasma clearance was 0.81 +/- 0.86 liters/h/kg, and the apparent steady-state volume of distribution was 4.68 +/- 2.02 liters/kg. The mean elimination half-life of pleconaril was 5.7 h. The mean plasma pleconaril concentrations at both 12 h (250.4 +/- 148.2 ng/ml) and 24 h (137.9 +/- 92.2 ng/ml) after the single 5-mg/kg oral dose in children were higher than that from in vitro studies reported to inhibit > 90% of nonpolio enterovirus serotypes (i.e., 70 ng/ml). Thus, our data support the evaluation of a 5-mg/kg twice-daily oral dose of pleconaril for therapeutic trials in pediatric patients with enteroviral infections. (+info)
Hemolysis associated with 25% human albumin diluted with sterile water--United States, 1994-1998.
Since 1994, a shortage of 5% human albumin, a product used off-label during therapeutic plasma exchange (TPE), has existed in the United States. Because of this shortage, hospital pharmacists may prepare 5% solution of human albumin by diluting 25% human albumin with 0.9% NaCl or, when sodium load is a concern, 5% dextrose. However, if sterile water alone is used as the diluent, the osmolarity (tonicity) of the albumin solution is reduced and may cause hemolysis in recipients. This report describes two of 10 episodes of hemolysis (one fatal) among persons who received 25% human albumin diluted with sterile water and emphasizes that sterile water alone should not be used to dilute albumin. (+info)
Nanoelectrospray--more than just a minimized-flow electrospray ionization source.
The comparison between electrospray ionization (ESI) mass spectra from NaCl solutions with and without analyte obtained under ionspray and nanospray conditions reveals different mass spectral behavior of the two ESI techniques. This can be attributed to the different initial droplet sizes which are in the microns range for ionspray, while in nanospray they are believed to be about one order of magnitude smaller. In the context of the widely accepted uneven-fission model, nanospray would then enter one fission generation later; in addition, a higher initial droplet surface charge density in nanospray results in early fissions without extensive evaporation and thus increase in sample and salt concentration. This rationalizes that ionspray spectra closely resemble nanospray spectra from solutions with about one order of magnitude higher salt concentrations, showing a higher tolerance of nanospray towards salt contamination. When the analyte is a peptide (in a solution containing a high molar surplus of salt), molecule ion formation effectively competes with salt cluster ion formation; when the analyte is a sugar, it is detectable beside a high salt concentration only with nanospray, indicating the supporting effect of surface activity on ion release in the case of peptides. A model is presented which explains the different mass spectral behaviour of ionspray and nanospray by suggesting different "predominant fission pathways" depending on the size of the initial droplets. (+info)
The relationship between pH and concentrations of antioxidants and vasoconstrictors in local anesthetic solutions.
pH affects the efficacy of local anesthetics by determining the percentage of the lipid-soluble base form of the anesthetic available for diffusion and penetration of the nerve sheath. The purpose of this study was to determine the relationship between pH and the concentrations of antioxidant and vasoconstrictor in dental local anesthetic solutions over real-time and after accelerated aging. Several batches of lidocaine and mepivacaine with vasoconstrictors were tested. Results showed that, immediately upon receipt from the manufacturers, three batches were below the USP pH limit (pH 3.3), and two batches contained less than the minimum limit of vasoconstrictors (90%). Real-time tests on batches that were within normal limits revealed that solutions were stable past 4 yr. Accelerated aging tests revealed a strong correlation between a decrease in pH and loss of antioxidants and vasoconstrictors. In conclusion, a quality batch of local anesthetic should remain efficacious long past the manufacturer's stated shelf life; a batch that is less than optimal, or one that is exposed to environmental stresses, will degrade rapidly, and efficacy may be affected by decreases in pH and loss of vasoconstrictor. pH may be an inexpensive, readily available screening test for efficacy of local anesthetics. (+info)
Epinephrine, magnesium, and dental local anesthetic solutions.
Plasma levels of magnesium were unaffected by the inclusion of epinephrine in lidocaine dental local anesthetic solutions in patients having third molar surgery under general anesthesia. (+info)
Stability-indicating high-performance liquid chromatographic assay of buspirone HCl.
The United States Pharmacopoeia high-performance liquid chromatographic (HPLC) assay method of buspirone is not able to discriminate buspirone from its degradation products. The purpose of this work is to develop a sensitive, selective, and validated stability-indicating HPLC assay for the analysis of a buspirone hydrochloride in a bulk drug. Buspirone HCI and its potential impurities and degradation products are analyzed on an Ultrasphere C18 column heated to 40 degrees C using a gradient program that contains monobasic potassium phosphate buffer solution (pH 6.9) and acetonitrile-methanol mixture (13:17) of 35% for 5 minutes, then increased to 54% in 5.5 minutes. The samples are monitored using a photo-diode array detector and integrated at 244 and 210 nm. The stress testing of buspirone HCI shows that buspirone acid hydrochloride is the major degradation product. The developed method shows a separation of buspirone degradation product and its potential impurities in one run. The stability of buspirone HCI is studied under accelerated conditions in order to provide a rapid indication of differences that might result from a change in the manufacturing process or source of the sample. The forced degradation conditions include the effect of heat, moisture, light, acid-base hydrolysis, sonication, and oxidation. The compatibility of buspirone HCI with some pharmaceutical excipients is studied under stress conditions. The linear range of buspirone HCI is between 5 and 200 ng/microL with a limit of quantitation of 2.5 ng/microL. The intraassay percentage deviation is not more than 0.38%, and the day-to-day variation was not more than 0.80%. The selectivity, repeatability, linearity, range, accuracy, sample solution stability, ruggedness, and robustness show acceptable values. (+info)
Investigation of effective anesthesia induction doses using a wide range of infusion rates with undiluted and diluted propofol.
BACKGROUND: The influence of infusion rate on the induction dose-response relation has not been investigated over a wide range of infusion rates. In this study, the authors defined the effect of different propofol infusion rates on the times and doses necessary to reach clinical induction of anesthesia. METHODS: The subjects of the study were 250 patients classified as American Society of Anesthesiologists physical status I or II aged 25-55 yr. For induction with undiluted propofol, 180 patients were allocated randomly to one of two groups of 90 patients each (A and B). Each group was further divided into nine subgroups (10 patients each) that were administered propofol infusion at rates of 10, 15, 20, 30, 40, 60, 100, 200, and 300 mg/kg-1/h-1. The remaining 70 patients (group C) were allocated randomly into seven subgroups (10 patients each), and these groups were induced with diluted propofol (0.5 mg/ ml) at the rates of 10, 15, 30, 60, 100, 200, and 300 mg/kg-1/ h-1. Group B was given crystalloid at the same infusion rates as group C via a catheter in the opposite arm. Induction time, induction dose, plasma arterial propofol concentration at loss of consciousness, and percentage decrease of systolic blood pressure were measured. A previously reported three-compartment model with an effect-site rate constant for propofol of 0.456/min was used to predict the induction time and dose at each infusion rate. RESULTS: The differences between predicted induction time and dose and the observed time and dose could be explained by factoring in the lag time from infusion site to central compartment (lag time circulation) and the amount of propofol in transit during this time (residual dose circulation). Residual dose circulation and lag time circulation correlated with infusion time from 20 to 60 s for undiluted and from 0 to 40 s for diluted propofol. At the infusion rates greater than 80 mg/kg-1/h-1, rapid circulation because of incomplete mixing in the central compartment decreased the excess induction time and dose. The use of diluted propofol significantly attenuated the decrease in systolic blood pressure provoked by the residual dose circulation. CONCLUSIONS: Induction dose and time are dependent on infusion rate in a complex manner, and residual dose circulation was a factor in overdose and hemodynamic depression. Hypotension during induction was attenuated by diluted propofol. (+info)
Exit-site care with ciprofloxacin otologic solution prevents polyurethane catheter infection in peritoneal dialysis patients.
OBJECTIVE: Mupirocin ointment and antiseptics are standard cleansing agents in routine exit-site care of peritoneal dialysis (PD) catheters, but these agents have a deleterious effect on polyurethane devices. We assessed the effectiveness of topical use of ciprofloxacin otologic solution for preventing exit-site infection (ESI) in PD patients with polyurethane catheters. DESIGN: Prospective study. SETTING: Service of Nephrology of an acute-care teaching hospital in Galdacano, Bizkaia, Spain. PATIENTS: A total of 164 patients with polyurethane catheters inserted was studied from start of continuous ambulatory PD to the end of a 24-month period. Patients were divided into two groups according to exit-site treatment protocols. INTERVENTION: Patients in group 1 (n = 86) were instructed on daily exit-site care with soap and water only; whereas patients in group 2 (n = 78) cleansed with soap and water, followed by application of a single-dose vial of 0.5 mL ciprofloxacin (1 mg) for application around the insertion site. MAIN OUTCOME MEASURES: Episodes of ESI and peritonitis. RESULTS: There were 67 episodes of ESI among patients in group 1 versus 9 episodes among patients in group 2 (p < 0.05), resulting in a rate of 0.41 and 0.06 episodes per patient-year of exposure, respectively (p < 0.001). Staphylococcus aureus ESI rate was 0.34 in group 1 versus 0.06 in group 2 (p = 0.001). Infections caused by Pseudomonas aeruginosa and other pathogens occurred in 11 patients in group 1 and in no patients in group 2 (p = 0.05). Peritonitis due to S. aureus ESI was significantly less frequent among patients treated with ciprofloxacin (1 vs 9 cases, p = 0.001). Removal of the catheter was necessary in 5 patients in group 1 and in no patients in group 2 (p < 0.05). CONCLUSION: Daily application of ciprofloxacin otologic solution at the exit site of PD patients with polyurethane catheters inserted significantly reduces the rate of ESI caused by S. aureus and other organisms, particularly P. aeruginosa. (+info)