Developmental toxicology studies of vancomycin hydrochloride administered intravenously to rats and rabbits.

Pregnant CD rats were given vancomycin intravenously in doses of 0, 40, 120, or 200 mg/kg on Gestation Days (GD) 6-15; pregnant New Zealand white rabbits were given 0, 40, 80, or 120 mg/kg intravenously on GD 6-18. Cesarean sections were performed on rats and rabbits on GD 20 and 28, respectively. In rats, maternal toxicity was indicated in the 120- and 200-mg/kg treatment groups by cortical tubular nephrosis.

General pharmacology of loracarbef in animals.

Loracarbef ((6R, 7S)-7-[(R)-2-amino-2-phenyl-acetamido]-3-chloro-8-oxo-1- azabicyclo [4.2.0]oct-2-ene-2-carboxylic acid, monohydrate, LY 163892, CAS 121961-22-6) is a carbacephem antibiotic targeted for use in the treatment of infectious disease.

Cardiovascular and autonomic pharmacology of the macrolide antibiotic LY281389 in anesthetized beagles and in isolated smooth and cardiac muscles.

As part of the preclinical safety evaluation process, an investigational macrolide antibiotic, LY281389, was examined for autonomic activity in isolated smooth and cardiac muscle preparations and for cardiovascular effects by intravenous infusion in anesthetized beagles. Concentration-dependent antagonism of acetylcholine and angiotensin I (guinea pig ileum), norepinephrine (rat vas deferens), and isoproterenol (guinea pig atria) was observed at LY281389 concentrations of greater than or equal to 10(-5) M. At LY281389 concentrations of greater than or equal to 10(-4) M, the response of the guinea pig ileum to electrical stimulation was also inhibited approximately 65 to 100%, indicative of potential anticholinergic or alpha-adrenergic activity.

Comparative effects of disulfiram and N-methyltetrazolethiol on spermatogenic development in young CD rats.

N-Methyltetrazolethiol (NMTT) and NMTT-containing cephalosporin antibiotics cause characteristic testicular lesions in young but not adult rats. In addition, NMTT-containing cephalosporins inhibit aldehyde dehydrogenase and have been associated with a disulfiram-like reaction in humans and animals. Therefore, the potential testicular toxicity of disulfiram (10, 30, or 100 mg/kg) was evaluated in 37-day-old rats given oral doses on Postpartum Days 6 through 36, and was compared to the toxicity induced by NMTT (100 mg/kg).

Comparison of in vitro and in vivo models to assess venous irritation of parenteral antibiotics.

The venous irritation potential of four parenteral antibiotics, tetracycline hydrochloride (TET), erythromycin lactobionate (ERY), amphotericin B (AMP), and cephaloridine (CEP), was evaluated in an in vivo model using the rabbit ear vein. Lateral ear veins of New Zealand White rabbits were infused for 1 hr with test solutions containing TET (0.25,2.