A novel buprenorphine (BUP) extended-release formulation (BUP-XR) produced as a lipid-encapsulated, low viscosity BUP suspension for SC injection to control pain was evaluated for pharmacokinetics and safety in Sprague–Dawley rats given either 0.65 mg/kg (low dose) or 1.30 mg/kg (high dose). The 2 dosage groups each contained 6 male and 6 female rats to determine whether BUP-XR behaved differently in male or female animals. Blood samples were obtained from each animal before BUP-XR administration and at 6, 24, 48, 72, 96, and 168 h after administration. For necropsy and injection-sitehistopathology evaluation, 3 animals of each sex from each test group were euthanized on day 8, with the remaining animals euthanized on day 15. Mean plasma BUP concentration peaked from 6 to 24 h in all test groups, then declined in a linear fashion. Quantifiable plasma BUP was measured in all male rats at all time points except for one low dose group sample taken at 168 h. Female rats had quantifiable plasma BUP at all time points except for 1 low dose group sample at 72 and 96 h, and 2 low dose group samples at 168 h. The low dose groups, whether male or female, had lower mean plasma BUP levels at all time points as compared with their high dose counterparts, and female rats had lower mean plasma BUP levels than male rats at all time points. Results indicate that a single BUP-XR dose at either dose concentration can reliably provide plasma levels of BUP reported in the literature to be therapeutically relevant for up to 72 h, although lower plasma BUP levels can be anticipated in female rats compared with male counterparts. Mild to moderate injection-site granulomatous inflammation was observed in 6 of 12 rats in the low dose group and 7 of 12 in the high dose group. This reaction is characteristic of lipid material designed to persist in situ.

Abdominal tissue, serum, and bile samples were obtained from 37 patients given a single, 2-g intravenous infusion of aztreonam immediately prior to an elective abdominal operation. Samples were obtained at 0 to 6 h after dosing. Mean concentrations in tissues and fluids and specimen/serum ratios are reported. Levels in tissue and bile exceeded the reported MICs for 90% of most members of the family Enterobacteriaceae for up to 6 h.Aztreonam is a new synthetic, monocyclic beta-lactam antibiotic which has exhibited excellent activity against aerobic and facultative gram-negative microorganisms. MICs of <1.0 ,ug/ml have been reported for many members of the family Enterobacteriaceae (14,15). The compound has demonstrated effective bactericidal activity against clinical isolates of Pseudomonas aeruginosa and appears resistant to many of the plasma-mediated beta-lactamases (9). Aztreonam has also exhibited interesting synergistic properties when combined with aminoglycosides against multiplyresistant gram-negative bacteria (1, 2). The present study was undertaken to determine the concentrations of aztreonam in various abdominal tissues and fluids obtained from patients during elective operative procedures.A total of 37 patients (20 males and 17 females), ranging in age from 14 to 82 years (mean, 51 years), in weight from 43.9 to 104.5 kg (mean, 69.5 kg), and in height from 139 to 182 cm (mean, 166 cm) participated in the study. Prior to patient screening, we received approval to carry out the study from both the Milwaukee County Medical Complex and the Medical College of Wisconsin human subject review committees. Written informed consent was obtained from the patients or appropriate relatives. The elective operations were performed for a variety of indications; the most common operations were resection of a neoplasm, hernia repair, fundoplication for reflux esophagitis, cholecystectomy, and colostomy removal or closure.A total of 22 patients received concomitant antibiotics, 19 for prophylaxis and 3 for preexisting infections. The antibiotics were given intravenously for surgical prophylaxis (cefazolin, cefoxitin, gentamicin, tobramycin, clindamycin, and penicillin G potassium), orally for gut sterilization (erythromycin and neomycin), and topically for irrigation of tissues (kanamycin and bacitracin). The systemic antibiotics had been previously shown to be inactive in the aztreonam assay. Two patients received trimethoprim-sulfamethoxazole postoperatively for urinary tract infections. Specimens from these patients were not included in the study because of potential interference with the aztreonam assay.Aztreonam (sterile powder; arginine blend; 2,000 mg) was reconstituted, diluted with 5% glucose in water to a final volume of 50 ml, and infused intravenously over a period of 5 min following the induction of anesthesia. A heparinized * Corresponding author. venous blood sample was obtained preoperatively for the determination of hemoglobin. During surgery, 1 to 2 g of normal (i.e., not infected or malignant) specime...

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When experimental drugs are used in the newborn, drug safety is of paramount importance. Unfortunately, there are often relatively large gaps between data collection and the time data are monitored and analyzed. In order to speed up the process of data retrieval and evaluation, an Internet‐based electronic data capture module was developed for pharmacokinetic and pharmacodynamic studies, allowing for rapid data entry, viewing and monitoring. The current study is a dose‐escalation clinical trial of stannsoporfin for the treatment of neonates, with hyperbilirubinemia, who are undergoing phototherapy. The goal of the study is to evaluate the ability of stannsoporfin to eliminate/reduce, the need for exchange transfusion. As part of an agreement with the FDA, the sponsor could not escalate to the next dose without a safety review by the sponsor and the FDA. An Internet‐based data entry application, with full edit checks and a query communication system, was designed so that safety data could be viewed anytime by the Medical Monitor, Data Safety Monitoring Board (DSMB) and the FDA. The presentation will illustrate the system's key features leading to the maximization of the quality and timeliness of data retrieval and analysis. Study implementation was characterized by the following: (1) transformation from paper was seamless; (2) no software installation was required; (3) the hospitals' computer systems were used; (4) study start‐up was not delayed; (5) quality was improved; and (6) overall costs were reduced. Clinical Pharmacology & Therapeutics (2005) 77, P70–P70; doi:

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