Vancomycin penetration into lung tissue was evaluated in thirty patients following the administration of 1 g of vancomycin as a 1 h i.v. infusion. Mean concentrations (range) of vancomycin in lung tissue were 9.6 (6.3-12.1) mg/kg at 1h, 5.7 (4.7-7.4) mg/kg at 2 h, 4.2 (0.8-6.5) mg/kg at 3-4 h, 2.4 (1.4-4.7) mg/kg at 6 h, and 2.8 (0.9-7.8) mg/kg at 12 h after the end of infusion. Ratios of lung tissue to serum concentration ranged 0.24 to 0.41 at 1 and 12 h, respectively. One of six patients observed at 6 h, and 3 of 7 patients at 12 h did not have detectable levels of vancomycin in lung tissue. A 1 h iv infusion of a 1 g dose of vancomycin does not achieve sustained lung concentrations above the MIC for susceptible staphylococci over a dosing interval of 12 h. Therefore, a more appropriate modality of administration, such as continuous infusion, should be considered.

Rufloxacin is a new long-acting, once-daily quinolone antibacterial agent. We evaluated inter-and intrasubject variations in pharmacokinetics of rufloxacin following oral administration of 400 mg (two capsules) under controlled conditions, at an interval of 2 weeks (periods I and II), to 12 healthy male subjects. Plasma and urine samples were collected up to 48 h after drug administration. Plasma drug levels determined by bioassay were higher than those measured by high-performance liquid chromatography, indicating that one or more active metabolites were formed. Individual high-performance liquid chromatography plasma rufloxacin concentrations were fitted with a one-compartment open model with first-order input. There were considerable variations in the plasma concentration-time profiles among subjects; for example, the elimination half-life in plasma varied from 14.6 to 95.5 h. However, pharmacokinetic parameters calculated for the two periods did not differ significantly. These results suggest that the intrasubject variation in the pharmacokinetics of rufloxacin is usually small in spite of the considerable intersubject variation.Rufloxacin (MF 934; Fig.

Some beta-aminoxypropionyl penicillins (3) and cephalosporins (4 and 5), planned on the basis of the hypothesis that the (methyleneaminoxy)methyl group (greater than C = NOCH2) could be a "bioisoster" of either aryls or other aromatic groups, were synthesized and assayed for their antimicrobial properties. Compounds 3-5, tested on Gram-positive and Gram-negative bacteria, both sensitive to enzyme inactivation and otherwise, exhibited an activity trend that was not substantially different from that of the corresponding phenylacetamido derivatives taken as terms of comparison.

The present study was designed to determine the effects of an antacid suspension containing magnesium hydroxide and aluminum hydroxide (30 ml of Maalox) on the oral bioavailability of rufloxacin (400 mg). Rufloxacin was administered oraly to 12 healthy volunteers according to a randomized, balanced, crossover design. Three treatments were administered to each subject, with a 10-day washout period between treatments; the treatments included rufloxacin alone, rufloxacin taken 5 min after antacid, and rufloxacin taken 4 h before antacid. Administration of antacid within 5 min before the administration of rufloxacin resulted in a substantial decrease in rufloxacin absorption, with a mean percent relative bioavailability compared with control values of 64% (range, 42 to 77%). Administration of antacid 4 h after the administration of rufloxacin slightly affected the absorption of the quinolone (mean relative bioavailablity, 87%; range, 51 to 110%Y). Antacids that contain magnesium and aluminum salts reduce the absorption of rufloxacin. The extent of this interaction depends on the time that elapses between administration of the two drugs.

Some (alpha-hydrazinobenzyl)cephalosporins, I (R = Me, CH2OAc, Cl) and II (R = Me, CH2OAc), structurally related (formula; see text) to cephalexin, cephaloglycin, and cefaclor have been prepared and evaluated in vitro for their antimicrobial activity. The synthesis involves the condensation of the chloride hydrochloride III (R = H or Me) with the 7-aminocephem derivatives IV. The hydrazino compound I (R = Cl), an analogue of cefaclor, resulted in being the most active compound of the series.