Zidovudine pharmacokinetics was determined in three human immunodeficiency virus type 1-seropositive women receiving zidovudine (200 mg orally every 4 h) from 19 to 39 weeks of pregnancy and postpartum. Zidovudine concentrations were measured using high-pressure liquid chromatography, and pharmacokinetic analyses were done using model-independent methods. For the pregnant versus postpartum periods, peak zidovudine levels (mean +/- 1 SD) were 3.9 +/- 1.7 mumol/l versus 4.3 +/- 0.04 mumol/l (P = .56); elimination half-lives were 1.3 +/- 0.6 versus 1.0 +/- 0.3 h (P = .41); areas under the concentration curve were 4.5 +/- 1.0 mumol/l x h and 6.8 +/- 0.5 mumol/l x h (P = .02); apparent total body clearances were 2.5 +/- 0.6 l/h/kg and 1.7 +/- 0.4 l/h/kg (P = .05); and apparent steady state volumes of distribution were 3.9 +/- 1.0 l/kg and 2.6 +/- 0.8 l/kg (P = .07), respectively. Umbilical cord serum levels ranged from 113%-127% of maternal levels. No persistent adverse effects of zidovudine therapy were seen in the three women or their babies.

The pharmacokinetics and safety of orally administered ciprofloxacin (Bay o 9867) were examined in 12 healthy male volunteers who received sequential doses of 250, 500, 750, and 1,000 mg. The individual and mean data were best described by biexponential disposition and elimination, assuming an apparent zero-order rate of absorption. The peak serum concentrations deterrmined from the individual data occurred at approximately 1.5 h after each dose and ranged from 0.42 to 4.2 ,ug/ml; the mean peak concentrations increased in proportion to the dose. The areas under the curve determined from the mean data were also proportional with respect to dose. The mean elimination half-lives calculated from pooled data were 4.1, 4.1, 6.9, and 6.3 h for doses of 250, 500, 750, and 1,000 mg, respectively. Longer half-lives but proportional area-under-the-curve values after the 750-and 1,000-mg doses implied that smaller fractions of ciprofloxacin were absorbed after these doses, although nonlinear kinetics could not be ruled out. The mean serum concentrations 12 and 24 h following each dose were -0.08 and 0.01 ,ug/ml, respectively. The urinary concentrations ranged from 30 to 500 ,ug/ml for at least 12 h after administration and were -9 ,ug/ml at 24 h following each dose. The urinary recovery level of unchanged ciprofloxacin over a 24-h period ranged from 28 to 44%. The mean renal clearances for each dose ranged from 300 to 500 ml/min. Ciprofloxacin was well tolerated, and no significant clinical or laboratory abnormalities were observed.Ciprofloxacin (Bay o 9867), a new quinolone derivative that is chemically related to nalidixic acid and norfloxacin, is currently undergoing microbiologic, pharmacokinetic, and clinical evaluation. The MICs of ciprofloxacin for 90% of the Enterobacteriaceae, Pseuidomnonas aeruiiginiosa, Hatemophiluis influenzae, Staphylococcus aureiis (including methicillin-resistant S. aiureuts), streptococcal, and Btacteroidesfragilis strains which have been tested including strains resistant to gentamicin and many third gei eration cephalosporins, range from 0.008 to 2.0 jig/ml (3,6,13).Ciprofloxacin was originally developed as an oral agent similar to nalidixic acid for the treatment of urinary tract infections. However, due to its excellent activity against gram-negative bacteria, development of a parenteral product is currently underway for use in the treatment of systemic bacterial infections. The purpose of this study was to determine the pharmacokinetic disposition and tolerance of orally administered ciprofloxacin in healthy volunteers after sequential increasing doses. MATERIALS AND METHODSSixteen healthy males (ages 22 to 26 years) were randomly selected to receive either ciprofloxacin (12 subjects) or a placebo (4 subjects). Before the study and before each of the four weekly doses, all of the subjects underwent physical examinations, including electrocardiograms, complete blood counts, platelet counts, a panel of 20 serum chemistry tests, urinalysis, and a stool test for occult blood. Another examin...

No abstract

The new second-generation cephalosporins, cefonicid, ceforanide, and cefuroxime, have recently become available. These agents are generally less active against gram-positive cocci than first-generation cephalosporins and, at best, equal to cefoxitin and cefamandole against many gram-negative bacteria. Cefuroxime, however, is the most active cephalosporin for β-lactamase-producing Haemophilus influenzae. These newer agents have superior pharmacokinetic characteristics over cefoxitin and cefamandole. Smaller doses, longer dosing intervals and, potentially, a reduction in total drug cost may be the real advantage of these agents. Open trials and a limited number of comparative studies have documented the effectiveness of cefonicid, ceforanide, and cefuroxime in the treatment of most mild-to-serious infectious diseases, although failures with cefonicid in the treatment of staphylococcal infections have been reported. Notably, cefuroxime has received approval for the treatment of common pediatric bacterial meningitis infections. Replacement of cefamandole or cefoxitin with one of these “longer-acting” agents may be cost-beneficial; however, clinicians must be on alert for the development of bacterial resistance or decreased efficacy.

Peritonitis has proven to be the major deterrent to the further growth of continuous ambulatory peritoneal dialysis (CAPD) as a treatment strategy for end-stage renal disease. The correct treatment of peritonitis remains unsettled as evidenced by the presence of advocates for oral, intravenous or intraperitoneal antibiotic administration. This study examines the pharmacokinetic parameters of intravenous vancomycin when employed in the therapy of peritonitis. One gram of intravenous vancomycin was administered during 7 episodes of peritonitis in 5 patients. Plasma and end-of-dwell dialysate levels were maintained above the minimum inhibitory concentration for Staphylococcus aureus and S. epidermidis for 7 days following this single dose of vancomycin. These data establish the existence of sustained intraperitoneal entry of intravenous vancomycin during peritonitis and raise for speculation its use as the sole therapy in most episodes of gram-positive peritonitis.