Intraocular penetration of rifampin in humans.

The penetration of rifampin into human aqueous humor was determined in 15 patients undergoing elective cataract surgery. Between 0.9 and 5.5 h after administration of a single 600-mg oral dose, concentrations ranged from 6.0 to 21.5 mg/liter in serum and from less than 0.2 to 1.3 mg/liter in aqueous humor.

Chemical and visual stability of amphotericin B in 5% dextrose injection stored at 4 degrees C for 35 days.

The chemical and visual stability of amphotericin B in 5% dextrose injection under refrigeration was assessed. Three admixtures of amphotericin B 0.1 mg/mL in 5% dextrose injection and three admixtures of amphotericin B 0.25 mg/mL in 5% dextrose injection were aseptically prepared in polyvinyl chloride (PVC) bags. Immediately after preparation (at time zero), six 5-mL samples were aseptically transferred from each admixture to sterile collection tubes. Three of the samples from each admixture were quick-frozen for later assay by stability-indicating high-performance liquid chromatography (HPLC), and the other three were immediately assessed for pH. Each of the six admixtures was also assessed visually under fluorescent light and 2x magnification for color change, turbidity, gas evolution, and precipitation. The admixtures were stored in PVC bags at 4 degrees C and protected from light. Six 5-mL samples were withdrawn from each admixture at 10, 21, and 35 days. Three of the samples from each admixture were assessed for pH, and three were quick-frozen for subsequent HPLC assay. There was no substantial loss or deterioration of amphotericin B during the 35-day study. At no time was the mean concentration of amphotericin B in the samples less than 96.4% of the concentrations at time zero for the 0.1-mg/mL samples or less than 96.6% of the time zero concentrations for the 0.25-mg/mL samples. There were no appreciable changes in pH, and there was no visual evidence of instability in any of the samples.(ABSTRACT TRUNCATED AT 250 WORDS)

Teicoplanin pharmacokinetics in healthy volunteers after administration of intravenous loading and maintenance doses.

Teicoplanin is an investigational glycopeptide antibiotic that is structurally and microbiologically similar to vancomycin. Since teicoplanin possesses a very long elimination half-life, the manufacturer suggests that the drug be administered every 12 h for the first day of therapy and once daily thereafter. We studied the multiple-dose (6 mg/kg per dose) pharmacokinetics of teicoplanin in volunteers following intravenous administration every 12 h for 5 days and then every 24 h for 9 days in an attempt to identify the optimal duration of the every-12-h loading-dose regimen. Multiple serum samples were obtained throughout the study, including intensive sampling after the first and last doses; urine was collected during the entire study. A three-exponential equation was fitted to the serum concentration data. The mean terminal-phase half-life was 157 +/- 93 h. Concentrations of teicoplanin in serum similar to those observed after the administration of the last dose (day 14) were observed following the fourth or fifth dose given every 12 h. Therefore, it is suggested that for clinical dosing regimens for teicoplanin, dosing every 12 h for approximately 48 h should be used, followed by once-daily dosing thereafter.

Metabolism and the fluoroquinolones.

Quinolones differ considerably with respect to the relative importance of nonrenal drug elimination mechanisms. The extent to which the fluoroquinolones undergo biotransformation in the liver ranges from approximately 50 percent for pefloxacin to about 6 percent for ofloxacin. Although glucuronide conjugates have been identified as minor metabolites for some agents, most metabolic reactions involving quinolones occur through microsomal oxidative mechanisms at the cytochrome P-450 site. These metabolic alterations involve the piperazinyl moiety and usually result in compounds with significantly less microbiologic activity than the parent drugs. Of particular importance is the varying extent of formation of the oxoquinolone metabolite with all fluoroquinolones except ofloxacin. Available evidence suggests that the inhibition of metabolism of drugs such as theophylline and caffeine by quinolones is related to the production of the oxoquinolone metabolite. With all antibiotics, differences in microbiologic activity and pharmacokinetics influence the choice of one agent over another for individual patient selection or consideration for hospital formulary inclusion. For the quinolones the degree and type of metabolism may be a strong factor in this selection process.

Comparative pharmacokinetics of cefotetan and cefoxitin in patients undergoing hysterectomies and colorectal operations.

Forty patients undergoing hysterectomy and 16 patients undergoing colorectal surgery were given intravenous 2 g doses of cefotetan (20 in the hysterectomy group and 8 in the colorectal group) or cefoxitin (20 in the hysterectomy and 8 in the colorectal group) before surgery. Serum samples were obtained simultaneously with tissue samples. Concentrations of each drug in serum and tissue were measured by high-pressure liquid chromatography. In both experiments, the composite drug concentration profile as a function of time in serum was consistent with that observed in nonsurgical patients; that is, a half-life of approximately 3.5 hours and 0.8 hours for cefotetan and cefoxitin, respectively. This also was true of tissue kinetics, in that tissue profiles appeared parallel to, but somewhat lower than, serum. At 20 minutes after administration, the peak myometrium concentration was 158 micrograms/g for cefotetan, and the corresponding serum concentration was 298 micrograms/ml. For cefoxitin, the corresponding values were 66 micrograms/g and 101 micrograms/ml. At 47 minutes, the cefotetan tissue and serum concentrations were 29 micrograms/g and 235 micrograms/ml respectively, and the corresponding values for cefoxitin were 15 micrograms/g and 43 micrograms/ml. Similar relationships were observed with these drugs in colorectal tissue. Although both antibiotics provide good concentrations during the early phase of surgery, cefotetan's concentrations persisted longer, which may be relevant in the prevention of infection in prolonged surgical procedures.

Patient-controlled analgesia using butorphanol for postoperative pain relief: an open-label study.

Patient-controlled analgesia (PCA) has been studied extensively for the treatment of postoperative pain using narcotic analgesics. Butorphanol, a nonnarcotic injectable analgesic, has not previously been investigated using this drug delivery mechanism. Twenty-five patients undergoing general abdominal surgery and general anesthesia used a PCA device with butorphanol as the analgesic agent. Most patients (84%) were able to obtain excellent postoperative pain relief. The role of butorphanol in the management of postoperative pain should be expanded to include patient-controlled drug delivery.