Oxygen gas-filled microparticles provide intravenous oxygen delivery.

We have developed an injectable foam suspension containing self-assembling, lipid-based microparticles encapsulating a core of pure oxygen gas for intravenous injection. Prototype suspensions were manufactured to contain between 50 and 90 ml of oxygen gas per deciliter of suspension. Particle size was polydisperse, with a mean particle diameter between 2 and 4 µm. When mixed with human blood ex vivo, oxygen transfer from 70 volume % microparticles was complete within 4 s. When the microparticles were infused by intravenous injection into hypoxemic rabbits, arterial saturations increased within seconds to near-normal levels; this was followed by a decrease in oxygen tensions after stopping the infusions. The particles were also infused into rabbits undergoing 15 min of complete tracheal occlusion. Oxygen microparticles significantly decreased the degree of hypoxemia in these rabbits, and the incidence of cardiac arrest and organ injury was reduced compared to controls. The ability to administer oxygen and other gases directly to the bloodstream may represent a technique for short-term rescue of profoundly hypoxemic patients, to selectively augment oxygen delivery to at-risk organs, or for novel diagnostic techniques. Furthermore, the ability to titrate gas infusions rapidly may minimize oxygen-related toxicity.

A nationwide survey of physician office visits found that inappropriate antibiotic prescriptions were issued for bacterial respiratory tract infections in ambulatory patients.

OBJECTIVE: Correlations between probabilities of resistance and the frequencies with which antibiotics were prescribed for treating bacterial respiratory infections were examined in a nationwide ambulatory population. STUDY DESIGN AND SETTING: The data of a nationwide probability sample survey of visits to physician offices in the United States in 1999 were used to conduct this study of drug use. A clinical pharmacologist identified antibiotics prescribed during those visits using a large online database. The participating physicians diagnosed the bacterial respiratory infections. An infectious disease expert determined the probabilities of bacterial resistance from a nationwide antibiotic surveillance database. RESULTS: Various bacterial respiratory infections were diagnosed during 6.5% of physician office visits in 1999. One or more antibiotics were prescribed during 51.0% of those visits. The probabilities of resistance to the most frequently prescribed antibiotics varied from 20% to 40% and showed a weak positive correlation with the frequencies of antibiotic prescriptions. CONCLUSION: A significant number of inappropriate antibiotic prescriptions were issued for infections with a high probability of bacterial resistance to the prescribed antibiotics.

The Influence of Dirithromycin on the Pharmacokinetics of Cyclosporine in Healthy Subjects and in Renal Transplant Patients.

The effect of a standard regimen of the investigational macrolide antibiotic, dirithromycin, on the single-dose kinetics of orally administered cyclosporine (CSA) was investigated in healthy young males and on the steady-state disposition kinetics of cyclosporine in a panel of renal transplant patients. Eight male volunteers participated after giving informed consent. CSA was administered in three single doses (15 mg kg(minus sign1) p.o. each) in each of three phases: (1) prior to a 14-day regimen of dirithromycin; (2) at the end of a 14-day regimen of dirithromycin (500 mg p.o. qAM); and (3) 2 weeks after the last dose of a 14-day regimen of dirithromycin. Pharmacokinetic parameters of CSA were estimated, and the differences among treatments were assessed by analysis of variation. No significant differences among treatment (phase) means were detected (p < 0.05). We conclude that a typical 14-day regimen of dirithromycin failed to alter the disposition kinetics of CSA when taken orally healthy young adult males. The effect of a standard regimen of dirithromycin on the steady-state disposition kinetics of orally administered CSA was investigated in a panel of 15 stable renal transplant patients. Pharmacokinetic parameters for CSA were evaluated prior to, during, and 2 weeks after discontinuing a 14-day (500 mg day(minus sign1)) oral regimen of dirithromycin. Dirithromycin elicited small but significant changes in the following parameters: C(av) was increased by 16% during dirithromycin treatment, and the changes in normalized C(av) were comparable. Likewise, C(SS,min) and normalized C(SS,min) were increased by 19% and 20%, respectively, during dirithromycin treatment. CSA oral clearance, CL/F(SS), decreased by 17% during dirithromycin treatment. C(SS,max) and normalized C(SS,max) were increased by 13% and 17%, respectively, during dirithromycin treatment but were not significantly different from those either before or after dirithromycin. The magnitude of the pharmacokinetic changes for CSA during dirithromycin treatment (<15% in normal subjects and 15--20% in renal transplant patients) when considered in the context of the therapeutic range of cyclosporine concentrations was relatively small, and not likely to warrant special attention to the dosing of CSA in such patients beyond routine whole-blood CSA and serum creatinine monitoring.

Bioavailability Study of Nizatidine When Administered in Food.

A single-center, open-label, four-way crossover study was performed in 22 healthy adult subjects to determine the relative effect and significance of certain foods on the bioavailability of nizatidine. Results indicate that administration of nizatidine mixed with apple sauce, cranberry juice, or vegetable juice reduces the bioavailability approximately 30--40% relative to administration of a nizatidine capsule with water. The reduction of bioavailability appears to be primarily due to reduced extent of absorption. The mechanism of this effect was not investigated.