Penetration of loracarbef into the maxillary sinus: a pharmacokinetic assessment.

Loracarbef, a beta-lactam antibiotic of the carbacephem class, is active in vitro against pathogens associated with acute maxillary sinusitis. To study the extent and duration of maxillary sinus fluid penetration after administration of loracarbef, 20 patients (10 men, 10 women; average age, 41 +/- 13 years) with acute sinusitis were treated with loracarbef 400 mg every 12 hours for 10 days. A lavage catheter was inserted into the maxillary sinus, and 150-microL sinus fluid samples were obtained at 0 (baseline), 0.5, 1, 1.5, 2, and 2.5 hours after the first dose and at 24 and 48 hours (12 hours after the second and fourth doses, respectively). Venous blood samples were obtained at the same times. Maxillary fluid and serum samples were frozen immediately at -20 degrees C to -70 degrees C until later bioassay using a direct agar diffusion method. Excluding missing data or inappropriately timed samples, the mean (+/- SD) sinus fluid concentrations were 0.16 +/- 0.12 microgram/mL at baseline, 0.23 +/- 0.17 microgram/mL at 0.5 hour, 1.11 +/- 1.44 micrograms/mL at 1 hour, 1.63 +/- 2.07 micrograms/mL at 1.5 hours, 1.75 +/- 2.01 micrograms/mL at 2 hours, and 1.60 +/- 1.96 micrograms/mL at 2.5 hours after dose. The mean sinus fluid concentration before the third dose (approximately 12 hours after the second dose) was 1.01 +/- 0.89 microgram/mL and before the fifth dose (approximately 12 hours after the fourth dose) was 0.88 +/- 0.90 microgram/mL. Taking the highest sinus fluid concentration measured in each patient, the mean peak sinus fluid concentration was 2.12 +/- 1.98 micrograms/mL (range, 0 to 6.7 micrograms/mL). The pretherapy peripheral leukocyte count appeared to have a statistically significant association (P < 0.01) with loracarbef sinus fluid penetration as estimated by the sinus fluid area under the concentration-time curve at 0 to 2.5 hours. Loracarbef 400 mg twice daily achieved sinus fluid concentrations that appeared to exceed the minimum concentration required to inhibit 90% of relevant acute sinusitis pathogens throughout the 12-hour interdose interval in most patients with acute maxillary sinusitis.

The comparative efficacy and safety of clarithromycin and amoxycillin in the treatment of outpatients with acute maxillary sinusitis.

The efficacy and safety of clarithromycin and amoxycillin in the treatment of acute maxillary sinusitis were compared in a single-blind, multicentre outpatient study. Fifty patients were randomly assigned to receive either clarithromycin 500 mg 12-hourly or amoxycillin 500 mg 8-hourly orally. Clinical signs and symptoms, sinus culture and blood and urine laboratory profiles were assessed prior to treatment, at four to six days during treatment, and within 48 h of the end of therapy (usually 9-11 days). Patients from whom beta-lactamase producing strains were isolated were excluded from the study. Both antibiotics achieved a clinical success rate of 91% within 48 h post-treatment; radiological resolution or improvement was observed in 91% of patients treated with clarithromycin and 89% of patients who received amoxycillin. Bacteriological cure was achieved in 88% and 91% of evaluable patients for clarithromycin and amoxycillin, respectively. Adverse events were reported for 16% of patients in the clarithromycin group compared to 26% in the amoxycillin group. Gastrointestinal disturbance was the most commonly occurring adverse event in both groups. The results of this study suggest that clarithromycin is as effective and well tolerated as amoxycillin in the treatment of acute maxillary sinusitis.

Nasal decongestant effect of oxymetazoline in the common cold: an objective dose-response study in 106 patients.

Oxymetazoline has been used as decongesting nosedrops for more than 25 years but so far no objective dose-response study of the drug has been published. In this double-blind clinical trial the decongestant effect on the nasal mucosa by the doses and concentrations traditionally used of oxymetazoline were studied. In 106 men with acute infectious rhinitis, a significant dose-response relationship was found when the decongestant effect was measured objectively by anterior rhinomanometry and subjectively by symptom scores. The concentration and volumes of the drug recommended from clinical experience seem to be adequate.

Isomeric phenylthioimidazo[1,2-alpha]pyridines as anthelmintics.

A series of isomeric imidazo[1,2-alpha]pyridine-2-carbamates was prepared for testing as anthelmintics. The analogues were synthesized by reacting the appropriate 2-aminopyridine and methyl chloroacetylcarbamate. Steric hindrance in the 2,6-disubstituted derivative resulted in the formation of the isomeric 3-substituted analogue as the major product. Carbon-13 NMR proved useful in the structural assignments in this series. None of the analogues exhibited the potency of methyl 6-(phenylsulfinyl)imidazo[1,2-alpha]pyridine-2-carbamate when tested against Nematospiroides dubius in mice.

Substituted imidazo[2,3-alpha]pyridine-2-carbamate anthelmintics.

Anthelmintic efficacies of a series of 6-substituted methyl imidazo[1,2-alpha]pyridine-2-carbamates were compared to similarly substituted benzimidazole-2-carbamates. With only one exception, methyl 6-benzoylimidazo[1,2-alpha]pyridine-2-carbamate, both classes of compounds exhibited similar activity vs. Nematospiroides dubius in mice. Preliminary screening indicated methyl 6-(1,2,2-trichloroethenyl)imidazo[1,2-alpha]pyridine-2-carbamate to be the most potent derivative in the series. However, evaluation in sheep indicated that its anthelmintic spectrum was inferior to methyl 6-(phenylsulfinyl)imidazo[1,2-alpha]pyridine-2-carbamate.

Measurement of eustachian tube function using sonotubometry.

Sound transport through the Eustachian tube in normal ears has been recorded using sonotubometry (Virtanen, 1978). It was found that only 66% of the ears had sound transport through the tube when swallowing. Despite the fact that all ears had adequate aeration of the middle ear at the time of testing, 34% of the ears had no sound passage when swallowing. The explanation for this phenomenon is discussed. Also, it is concluded that this test may reflect Eustachian tube patency during swallowing--and not tubal function.

Methyl 6-(phenylsulfinyl)imidazo[1,2-a]pyridine-2-carbamate, a potent, new anthelmintic.

A series of methyl imidazo-[11,2-a]pyridine-2-carbamates was synthesized for anthelmintic testing. The preparation of this class of compounds was simplified by utilization of a novel one-step condensation of the appropriately substituted 2-aminopyridine and methyl chloroacetylcarbamate. The most potent compound, methyl 6-(phenylsulfinyl)-imidazo[1,2-a]pyridine-2-carbamate, was orally effective against a broad range of helminths in sheep and cattle, at a dosage of 2.5 mg/kg. Limited trials in swine and dogs demonstrated anthelmintic activity at higher dosages. Limited observations in sheep and cattle indicated that, in both species, a single oral dose of 200 mg/kg was well tolerated.

4-amino-6-(trichloroethenyl)-1,3-benzenedisulfonamide, a new, potent fasciolicide.

The synthesis and fasciolicidal activity of 4-amino-6-(trichloroethenyl)-1,3-benzenedisulfonamide are reported. A single dose of 15 mg/kg was effective in removing over 90% of immature Fasciola hepatica from sheep (6 weeks after infection) and calves (8 weeks after infection). A 2.5 mg/kg dose removed over 90% of mature (16 weeks old) liver fluke from sheep. Single oral doses up to 400 mg/kg were tolerated by sheep without gross toxic symptoms.