Differences in extent of amoxicillin absorption from various regions of the gastrointestinal tract were determined and compared with the same dose administered orally. Nine healthy men were intubated at a proximal (duodenum or jejunum) or distal (ileum or colon) site with use of a 15-foot double lumen nasointestinal tube. Amoxicillin solutions (375 mg in 120 ml water) were delivered on 2 successive days as a bolus or a 4-hour infusion. Subjects were reintubated at another site and amoxicillin administration was repeated. Subjects with colonic intubation received only infusions. Finally, all subjects received an oral dose of amoxicillin solution. Plasma samples were obtained at 16 time points over a 10-hour period and assayed for amoxicillin by use of an HPLC method. Area under the concentration-time curve and the maximum plasma concentration were computed to evaluate amoxicillin absorption. Amoxicillin absorption was rate and site dependent in the gastrointestinal tract. The drug was well absorbed in the duodenum and jejunum, with no significant differences in absorption when administered as a bolus or 4-hour infusion, but absorption was decreased and rate dependent in the ileum, where more drug was absorbed as an infusion compared with a bolus. Amoxicillin was unabsorbed when infused in all colonic regions.
Pentazocine, butorphanol, nalbuph ine, and buprenorphine are mixed agon ist-antagonist opio ids that are effective analgesics, with less abuse potent ial than the agonists morphine, propox yphene , and codeine. The dual properties of the agonist-antagonists are largely explained by their varying actions at the postulated three types ()t, x , and u) of opioid receptors. The agonist-antagonists are classified as either morphine-like or nalorphine-like, based on their acute effects and withdrawal symptoms after chronic dosing. Buprenorphine is morphine-like, while the other drugs are nalorphine-like. These agents vary in the duration of analgesia, with pentazocine having a mean action of three hours and buprenorphine greater than six hou rs. The hemodynami c effects of nalbuph ine and buprenorphine generally resemble those of morphine, while pentazocine and butorphanol increase cardiac workload , blood pressure, and pulmonary arter y pressure. The agonist-antagonists have ceilings for respiratory depression, whereas the agonists produce dose-dependent depression . Agonist-antagonists generally produce less increase in biliary ductal pressure than does morphine. The major clinical limitations are that agonistdependent patients may experience unpleasant subjective effects, when treated with the agonist-antagonists, and the nalorphine-like agents can produce psychotomimetic effects . More clinical experience is needed to rank the abuse potential within this group of opioids. The newer agents are being studied for oral use in acute and chronic pain .
Administration of silver nitrate 1070 solut ion into the eyes of the newborn has pro ven effective in the prophylaxis of gonococcal neonatal conjunctivitis. Silver nitrate, however, is not acti ve against Chlamydia trachomatis , the most common cause of neonatal con junctivitis. Also , silver nitrate commonly is associated with substantial chemical irritation. For these reasons, alternative agents are receiving increasing attention. Recently , erythromycin 0.5070 and tetracycline 1070 ophthalmic ointments were recommended by the Centers for Disease Control Venereal Disease Control Division for prophylaxis of neonatal conjunctivitis. Erythromycin has pro ven at least as effect ive as silver nitrate for gonococcal prophylaxis, can prevent chlamydial conjunctivitis in infants born to Chlamydia-positive mothers, and is associated with minimal complications . Clinical studies, however, demonstrating significant differences between erythromycin and tetracycline ophthalmic ointments are lacking. Well-controlled clinical studies comparing silver nitrate, erythromycin, and tetracycline prophylaxis are needed to determine the relative effectiveness of these agents.
In a double-blind study, a timed-release tablet containing carbinoxamine maleate 8 mg and pseudoephedrine hydrochloride 120 mg was compared with placebo for the treatment of signs and symptoms of nasal allergy. Ninety-four adults with rhinitis caused by grass or ragweed allergy were paired according to severity of symptoms and nasal congestion, then assigned randomly to drug or placebo. After baseline measurements were taken, three doses of drug or placebo were given at 12-hour intervals. The active drug was significantly better than placebo in relieving the following symptoms: nasal congestion, nose blowing, sneezing, nasal pruritus, rhinorrhea, ophthalmic pruritus, and sniffles. Improvement over baseline in mean total nasal air flow also was greater in subjects given active drug. The incidence of nonspecific symptoms, including possible drug side effects, was similar between groups. We conclude that the timed-release tablet is safe and effective therapy for the treatment of signs and symptoms of nasal allergy.
From September 1989 through July 1991, before commercial availability, Survanta (beractant intratracheal suspension), a modified bovine-derived surfactant used for prevention and treatment of neonatal respiratory distress syndrome, was made available to 231 neonatal intensive care units in the United States and Canada under a Treatment Investigational New Drug protocol. Results of this open clinical experience are reported. Investigators could give one dose of Survanta soon after birth to neonates weighing 600 to 1250 g (prevention strategy). Neonates weighing 600 to 1750 g who were not treated at birth could begin Survanta therapy if respiratory distress syndrome developed within 8 hours of birth (rescue strategy). All neonates could receive up to three more doses over the first 48 hours of life at minimum intervals of 6 hours if they met retreatment criteria. Qualifications for enrollment closely matched those used in previous randomized controlled clinical trials. This report includes results from 8168 neonates who completed the study. Treatment Investigational New Drug rates for intracranial hemorrhage, patent ductus arteriosus, pulmonary hemorrhage, pulmonary air leaks, bronchopulmonary dysplasia, death or bronchopulmonary dysplasla, pulmonary interstitial emphysema, pretreatment sepsis, and posttreatment sepsis were less than for treated neonates in the controlled trials and survival was equivalent across studies. Problems with treatment administration were reported with 30.4% of doses, while adverse events were reported in 0.5% of neonates. The results of the Treatment Investigational New Drug protocol revealed no new safety concerns associated with the widespread use of Survanta and confirmed the safety profile established in earlier controlled trials.
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