Orally administered cefpodoxime proxetil for treatment of uncomplicated gonococcal urethritis in males: a dose-response study.

An open-label, dose-response study of cefpodoxime proxetil (CPD), an expanded-spectrum cephalosporin, was conducted with 58 males with uncomplicated Neisseria gonorrhoeae infections with single doses of 600, 400, 200, 100, or 50 mg of CPD administered orally by tablet. CPD eradicated N. gonorrhoeae in all 50 evaluable patients (10 per group) at all doses studied. Eight of the isolates eradicated were beta-lactamase-producing organisms. Two patients reported three side effects, nausea, vomiting, and diarrhea, which were mild and resolved without intervention or sequelae. There were no clinically remarkable drug-related changes in vital signs or clinical laboratory assays. Results show that single oral doses of CPD are an effective and well-tolerated treatment for uncomplicated N. gonorrhoeae infection in males at doses as low as 50 mg.

Human safety and pharmacokinetics of a single intramuscular dose of a novel spectinomycin analog, trospectomycin (U-63,366F).

In this study, local and systemic tolerance and pharmacokinetics of trospectomycin sulfate in human beings were evaluated for the first time. Trospectomycin sulfate (U-63,366F; trospectomycin) or sterile saline was administered to 96 healthy male volunteers in doses ranging from 0.25 ml (75 mg) to 3.3 ml (1,000 mg) in a single intramuscular injection in a double-blind, randomized design. Volunteers were screened to establish baseline vital signs and laboratory test values. Pain and tenderness at the injection site, which occurred at doses of 450 mg and above, were the most common side effects; they were mild in severity and transient. Adverse drug experiences reported by subjects included nausea, dizziness, light-headedness, diaphoresis, costal pain, and perioral numbness. The perioral numbness (paresthesia) experienced at doses of 750, 900, and 1,000 mg was probably drug related. No Clostridium difficile toxin was detected in fecal samples. Pharmacokinetic calculations based on data obtained by high-performance liquid chromatography showed that after a 1,000-mg intramuscular dose of trospectomycin (3.3 ml), the serum mean half-life was 1.85 h (1.70 to 2.02 h), mean area under the serum concentration-time curve was 140.2 micrograms.h/ml and was linear with dose, mean peak concentration was 28.3 micrograms/ml (20.4 to 34.7 micrograms/ml), mean time to maximum concentration was 71 min (30 to 120 min), and the elimination rate constant was 0.307 h-1. The elimination rate constant and half-life did not vary with dose. Little trospectomycin was detected in 2-day fecal collections. A few randomly occurring abnormal clinical laboratory test values and vital signs were observed. For the trospectomycin-treated group, creatinine phosphokinase increased substantially for 24 h after injection and then decrease through day 5, while serum glutamic oxalacetic transaminase and lactate dehydrogenase increased slightly.

Safety and pharmacokinetics of intravenously administered trospectomycin sulfate.

Local and systemic tolerance and drug pharmacokinetics were evaluated after a single intravenous infusion of 75 to 1,000 mg of trospectomycin or placebo in 96 healthy volunteers. No clinically significant changes, trends, or abnormalities were observed in the vital signs, electrocardiograms, or laboratory test results; however, there were some statistically significant dose effects or dose-by-time interactions on some of the measures. Mild, transient, local reactions at the infusion site were reported by 20% of the trospectomycin-treated and 22% of the placebo-treated subjects. No irritation of the surrounding tissue was noted when extravasation occurred. Mild, transient, perioral-facial numbness, which was probably drug-related, was the most commonly reported systemic adverse drug experience, occurring in 17 of 64 trospectomycin-treated subjects, but only at doses of 600 mg and above. Pharmacokinetic analyses showed that after a 1,000-mg intravenous dose of trospectomycin, the mean serum half-life was 2.18 hr, the mean area under the curve (AUC) was 157.0 hr x micrograms/ml, the mean maximum concentration (Cmax) was 82.4 micrograms/ml, the mean time to maximum concentration was 25.0 min, and the elimination rate (Ke) was 0.33 hr-1. The Ke and half-life did not vary with dose, and both Cmax and AUC showed a strong linear trend. From 48% to 62% of the dose was excreted in the urine during the first 48 hours after infusion. Under the conditions of this study, intravenous trospectomycin was well tolerated by human subjects at single doses up to and including 1,000 mg.

Clinical experience with cefmetazole sodium in the United States: an overview.

The clinical development programme for cefmetazole sodium included over 4000 patients treated by 78 investigators. Cefmetazole therapy was compared with that of cefoxitin sodium (cefoxitin) for the treatment of urinary tract, skin and soft tissue, lower respiratory, abdominal, and gynaecological infections (with cefoxitin-sensitive pathogens) and for the prevention of postoperative wound infection in patients undergoing surgical procedures. Both cefmetazole and cefoxitin were administered intravenously in all studies. Cefmetazole was as effective as cefoxitin in the treatment of the infections studied. In the surgical wound infection prophylaxis studies, multiple-dose cefmetazole therapy was more effective than multiple-dose cefoxitin therapy in patients undergoing lower gastrointestinal surgery; this difference approached statistical significance. Both multiple-dose and single-dose cefmetazole therapy were as effective as multiple-dose cefoxitin treatment in the other types of surgery studied. Clinical laboratory findings and adverse medical events reported among cefmetazole patients were similar to those observed in patients treated with cefoxitin.

Tolerance and disposition of cefpimizole in normal human volunteers after intramuscular administration.

Cefpimizole sodium (AC-1370, U-63196E) was administered intramuscularly in doses from 100 mg (0.5 ml) to 2,000 mg (two 3.5-ml doses) to healthy human volunteers in three double-blind placebo and positive-controlled (cefotaxime, cephalothin) single-dose studies and in two multiple-dose studies. Mild transient pain was observed at the injection site, but no erythema, petechia, necrosis, or atrophy was noted. Creatinine phosphokinase values were increased during the study in the cefpimizole- and placebo-treated groups but began to return to normal toward the end of the study period (day 5). They were not paralleled by a similar magnitude of elevation in serum glutamic oxalacetic transaminase and lactate dehydrogenase or by pain and tenderness. There were no clinically meaningful or statistically significant changes (P greater than 0.5) or trends in vital signs and no other patterns of drug-related clinical abnormalities noted in any of the laboratory measurements evaluated (hematology, chemistry, urinalysis). No serious side effects occurred during or after the study. Cefpimizole was well tolerated locally and systemically by all the subjects at all administered dosage levels. Cefpimizole concentrations in serum (microbiological assay) remained above 1 microgram/ml at 12 h after drug administration for all dose levels. The median peak concentrations in plasma for the 500- and 1,000-mg twice-daily dosages of cefpimizole were, respectively, 21.6 and 45.5 micrograms/ml on day 1, 16.2 and 43.7 micrograms/ml on day 3, and 20.1 and 41.4 micrograms/ml on day 6 of the study. The apparent terminal disposition half-life throughout the study was about 2.0 h. The median amounts of cefpimizole excreted in the urine for the first 12 h of each day evaluated were 370 and 1,071 mg on day 1, 416 and 972 mg on day 3, and 370 and 975 mg on day 6 for the 500- and 1,000-mg twice-daily dosages, respectively. Dose proportionally of cefpimizole was obtained for the 500- and 1,000-mg and the 2,000-mg groups. The absorption, distribution, and elimination of cefpimizole after multiple-dose intramuscular administration were uniform, were linear in relation to dose, and did not result in drug accumulation.

Pharmacokinetics and dose proportionality of cefpimizole in normal humans after intramuscular administration.

The pharmacokinetics of cefpimizole (free acid equivalents of cefpimizole sodium), a broad-spectrum cephalosporin antibiotic, were evaluated after intramuscular administration of single doses (dose range, 100 to 1,000 mg) and multiple doses (dose range, 500 to 2,000 mg) given b.i.d. for 6 or 11 days. The kinetics after intramuscular administration correspond to a one-compartment model with first-order input. The apparent volume of distribution of the absorbed dose averaged 18.6 +/- 3.4 (standard deviation) liters for 58 individuals; the absorption-phase and elimination-phase rate constants averaged 2.53 +/- 1.16 h-1 (half-life, 0.27 h) and 0.338 +/- 0.041 h-1 (half-life, 2.05 h), respectively; and the mean residence time was 3.43 +/- 0.43 h. The total body clearance of the absorbed dose after single-dose intramuscular administration was 102 +/- 13 ml/min. The primary route of elimination was renal with 73 to 83% of the administered dose excreted in the urine as unchanged drug. Renal clearance averaged 81 +/- 13 ml/min. Dose proportionality was obtained from area under the plasma curve, concentration maximum in plasma, and cumulative urinary excretion levels. Multiple-dose evaluation of intramuscular administration of cefpimizole indicated no apparent change in the absorption or elimination phases after b.i.d. dosing for 6 or 11 days. The kinetic parameters determined from multiple-dose plasma and urine levels were in close agreement with the same parameters calculated from single-dose results. No apparent accumulation of cefpimizole occurred, and nondetectable levels of drug were observed in the 24-h plasma and 24- to 48-h urine specimen after administration of the last dose. The kinetics of cefpimizole after intramuscular administration were similar to the kinetics obtained after intravenous infusion.

Smoking abstinence and small cell lung cancer survival. An association.

The prognostic implications of cigarette smoking were investigated in 112 patients with small cell lung cancer. Twenty had stopped smoking permanently before diagnosis (NS-Prior), 35 had stopped at diagnosis (NS-Dx), and 57 patients continued smoking (S). Therapies included chemotherapy alone or with radiation therapy, with or without thymosin fraction V. The survival difference among the three groups was statistically significant. The NS-Prior patients had the best survival, followed by NS-Dx patients and finally S patients. No S patient has survived, disease free, more than 96 weeks, while three NS-Prior and three NS-Dx patients are disease free 103 to 220 weeks after start of treatment. Thymosin, 60 mg/sq m, yielded survival benefits for the S group only. Continuation of smoking during the treatment of small cell lung cancer was associated with a poor prognosis, while discontinuation of smoking, even at diagnosis, may have beneficial effects on survival.

Effect of a single injection of lincomycin, spectinomycin, and linco-spectin on early chick mortality caused by Escherichia coli and Staphylococcus aureus.

The efficacies of lincomycin (L) and spectinomycin (S), alone and in various combinations (L/S), were determined against Escherichia coli (EC) and Staphylococcus aureus (SA) of avian origin, both in vitro and in vivo. L contributed significantly to L/S activity against SA, while S contributed significantly to L/S activity against EC, and L/S (2.5 mg L + 5.0 mg S) was more effective than either L or S against SA and EC. The suggested optimum dose for controlling early chick mortality caused by SA and EC is 2.5/5.0 mg of L/S per chick.