The cytotoxicity profile of various chemical entities was evaluated using two in vitro hepatocyte models. Liverbeads is a cryopreserved model consisting of primary hepatocytes entrapped in alginate beads. WIF-B9 is a hybrid cell line obtained by fusion of rat hepatoma (Fao) and human fibroblasts (WI38). Various reference hepatotoxicants were tested and ranked according to their equivalent concentration 50 (EC50) for various biochemical endpoints (lactate dehydrogenase (LDH) release, 3-(4,5 dimethylthiazol 2yl)-2,5-diphenyl-2H tetrazolium bromure (MTT) activity, adenosine triphosphate (ATP) and glutathione (GSH) levels). The ranking obtained was comparable in both models and consistent with previously published results on hepatocyte monolayers. Ketoconazole, erythromycin estolate, retinoic acid, telithromycin and alpha-naphthyl-isothiocyanate were among the most toxic chemicals in both models, with an EC50 < 200 microM. Troleandomycin, spiramycin, erythromycin, diclofenac, taurodeoxycholate, warfarin, galactosamine, valproic acid and isoniazid were found to be less toxic. Few marked differences, potentially linked to metabolism pathways, were observed between EC50s in the two models for compounds such as cyclosporine A (10 and > 831 microM) and warfarin (5904 and 1489 microM) in WIF-B9 and Liverbeads, respectively. The results obtained indicate that Liverbeads and WIF-B9 cells are reliable in vitro models to evaluate the hepatotoxic potential of a wide range of chemicals, irrespective of structure and pharmaceutical class.
Inhibition of canalicular bile acid efflux by medications is associated with clinical liver toxicity, sometimes in the absence of major liver effects in experimental species. To predict the hepatotoxic potential of compounds in vitro and in vivo, we investigated the effect of clinical cholestatic agents on [3H]taurocholic acid transport in regular and collagen-sandwich cultured human hepatocytes. Hepatocytes established a well-developed canalicular network with bile acid accumulating in the canalicular lumen within 15 min of addition to cells. Removing Ca2+ and Mg2+ from the incubation buffer destroyed canalicular junctions, resulting in bile acid efflux into the incubation buffer. Canalicular transport was calculated based on the difference between the amount of bile acid effluxed into the Ca/Mg2+-free and regular buffers with linear efflux up to 10 min. Hepatocytes cultured in the nonsandwich configuration also transported taurocholic acid, but at 50% the rate in sandwiched cultures. Cyclosporin A, bosentan, CI-1034, glyburide, erythromycin estolate, and troleandomycin inhibited efflux in a concentration-dependent manner. In contrast, new generation macrolide antibiotics with lower incidence of clinical hepatotoxicity were much less potent inhibitors of efflux. An in vivo study was conducted whereby glyburide or CI-1034, administered iv to male rats, produced a 2.4-fold increase in rat total serum bile acids. A synergistic 6.8-fold increase in serum total bile acids was found when both drugs were delivered together. These results provide methods to evaluate inhibitory effects of potentially cholestatic compounds on bile-acid transport, and to rank compounds according to their hepatotoxic potential.
Only penicillin has been adequately studied in treating syphilis during pregnancy. It is safe for the fetus and highly effective in doses currently recommended by the USPHS. Since these schedules appear to represent a minimal effective dose, smaller amounts should never be used. Whether higher doses would produce higher cure rates is not known. Penicillin is the drug of choice and the standard against which all others must be measured. Tetracyclines in any dose or form should not be used because of toxicity to both mother and child. Erythromycin (except the estolate) and cephalosporins are promising because of low toxicity, but their efficacy has not been established.
tablet eltocin ds
To investigate the mechanisms of erythromycin cholestasis, the effects of erythromycin estolate (EE) on the excretory function of the isolated perfused rat liver and on liver plasma membrane (LM) preparations were studied and compared to those of erythromycin base (EB) and lauryl sulfate (LS), added alone or in combination. EE (at 125 to 200 microM) caused dose-dependent reductions of bile and perfusate flows, bile acid (BA) excretion, and biliary BA concentration. The alterations of the excretory function were only in part due to the decreased perfusate flow. In contrast, both 200 and 300 microM concentrations of EB elicited similar choleretic responses, which were presumably related to the osmotic activity of the drug excreted in the bile. LS did not affect hepatic excretory functions. However, the simultaneous addition of EB and LS resulted in a rate of bile flow lower than that observed with EB alone. EE, but not EB, increased canalicular permeability to [14C]sucrose as measured by bile to plasma (B:P) ratio. Neither drugs altered [14C]erythritol B:P ratio. In LM preparations both Na+,K+- and Mg2+-ATPase activities were inhibited in a dose-dependent manner by EE, but not by EB. The data suggest that EE could affect bile flow by inhibiting cotransport of Na+ and BA and by altering LM permeability and support the view that the effect of erythromycins on the liver may be related to their surface activity.
eltocin medicine use
All splenectomized individuals are at risk of developing pneumococcal sepsis, but most reports fail to mention how many patients are given prophylactic penicillin therapy. Fourteen reported cases of postsplenectomy bacterial sepsis in patients receiving prophylactic penicillin therapy are reviewed. In only five cases, the patients had penicillin-sensitive pneumococcal infection. Hence, the exact frequency of the failure of penicillin prophylaxis cannot be calculated, but it appears to be very rare. Continuous antibiotic prophylaxis used indefinitely and pneumococcal vaccine are both strongly recommended for all children and adults undergoing splenectomy.
The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 1, 2004); MEDLINE (January 1966 to February 2004); EMBASE (January 1974 to August 2003); conference abstracts and reference lists of articles were searched. Study investigators and pharmaceutical companies were approached for additional information (published or unpublished studies). There were no constraints based on language or publication status.
Using prescription-event monitoring to determine whether erythromycin estolate was a more frequent cause of jaundice than erythromycin stearate or tetracycline 12 208 patients, for whom 5343 doctors had prescribed one of the three drugs, were identified by the Prescription Pricing Authority. Of the questionnaires sent to general practitioners about the possible occurrence of jaundice, 76% were returned. There were 16 reports of jaundice, of which four were attributable to gall stones, three to cancer, six to viral hepatitis, and only three were possibly related to an antibiotic. All three patients, in whom the antibiotic was a possible cause, had been treated with erythromycin stearate. No case was attributable to the estolate which had previously been suspected of being a more frequent cause of jaundice. Although the incidence is unknown, it is very unlikely to be more than one in 100.
eltocin tablet uses
The records of 124 children who were given the diagnosis of PL at our institution between 1993 and 2003 were retrospectively reviewed.
Thirty-one strains of Mycoplasma pneumoniae were tested for drug sensitivity to both josamycin (JM) and erythromycin (EM), to evaluate the efficacy of JM for mycoplasmal pneumonia in children. In addition to the sensitivity tests of 31 M. pneumoniae strains against JM and EM, 50 patients, between the ages of 3 years 1 month and 13 years 3 months, suspected of suffering from mycoplasmal pneumonia were treated with 50 or 200 mg JM tablets at an average daily dose of 43.1 mg/kg t.i.d. or b.i.d. for an average period of 14 days; an additional 31 patients between the ages of 2 years 9 months and 11 years, suspected of suffering from this disease were treated with tablet or dry syrup of EM, with the exception of EM estolate, t.i.d. or b.i.d. at an average daily dose of 72.5 mg/kg for an average period of 15 days. Patients were selected in 37 and 22 mycoplasmal pneumonic patients respectively for JM and EM. Clinical and bacteriological effects, efficacy and side effects of the drugs on this disease were studied and the following results were obtained. Drug sensitivity test Of all 31 strains tested for JM sensitivity the populations which exhibited 0.125 mcg/ml were most abundant (18/31, 58.1%) and MIC pattern of all strains were distributed from 0.0313 to 0.125 mcg/ml. In the EM group, 61.3% (19/31) of the populations were sensitive at 0.015 mcg/ml, exhibiting the dominant distribution pattern and MIC range of all organism varied from 0.0078 to 0.0313 mcg/ml. Resistant strains were found to neither JM nor EM. EM was approximately 2 to 10 times more active than JM in MIC evaluation. Clinical effects of JM by daily doses Clinical effects relative to the daily dose were evaluated in 3, 7, 10 days after administration of drugs. The response was favorable, according to assessments of the attending doctors, in 96.7, 100% and 95.8% of the patient group given JM in a daily dose of 40-49 mg/kg, the group to which the largest number of patients belonged. Similar favorable results were obtained by the assessments of Evaluation Committee, showing 86.7, 96.7% and 100% of favorable response. Upon comparison, in the same interval, of these results with those of the groups given EM in a daily dose of 50 mg/kg, the group in which the largest number of patients were seen, there was no significant difference in the assessments either of the attending doctors or of the Evaluation Committee.(ABSTRACT TRUNCATED AT 400 WORDS)