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A noncompliance rate of >30% is unsatisfactory. Whereas some variables significantly associated with compliance cannot be influenced (patient age; place of residence in town or city), others are amenable to modifications. These include the physician-patient interaction and the choice of antibiotic. Agents should be preferred that are well-accepted by patients, that enable short-term therapy with few daily doses and with a package that contains a dose-taking reminder.
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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.
Sectrophotometric analysis was used to determine the dissolution percentage of the tablets in vitro. High performance liquid chromatography and IBM/XT microcomputer was used to determine the bioavailability and pharmacokinetic parameters in vivo.
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The pathways of testosterone oxidation catalyzed by purified and membrane-bound forms of rat liver microsomal cytochrome P-450 were examined with an HPLC system capable of resolving 14 potential hydroxylated metabolites of testosterone and androstenedione. Seven pathways of testosterone oxidation, namely the 2 alpha-, 2 beta-, 6 beta-, 15 beta-, 16 alpha-, and 18-hydroxylation of testosterone and 17-oxidation to androstenedione, were sexually differentiated in mature rats (male/female = 7-200 fold) but not in immature rats. Developmental changes in two cytochrome P-450 isozymes largely accounted for this sexual differentiation. The selective expression of cytochrome P-450h in mature male rats largely accounted for the male-specific, postpubertal increase in the rate of testosterone 2 alpha-, 16 alpha, and 17-oxidation, whereas the selective repression of cytochrome P-450p in female rats accounted for the female-specific, postpubertal decline in testosterone 2 beta-, 6 beta-, 15 beta-, and 18-hydroxylase activity. A variety of cytochrome P-450p inducers, when administered to mature female rats, markedly increased (up to 130-fold) the rate of testosterone 2 beta-, 6 beta-, 15 beta-, and 18-hydroxylation. These four pathways of testosterone hydroxylation were catalyzed by partially purified cytochrome P-450p, and were selectively stimulated when liver microsomes from troleandomycin- or erythromycin estolate-induced rats were treated with potassium ferricyanide, which dissociates the complex between cytochrome P-450p and these macrolide antibiotics. Just as the testosterone 2 beta-, 6 beta-, 15 beta-, and 18-hydroxylase activity reflected the levels of cytochrome P-450p in rat liver microsomes, so testosterone 7 alpha-hydroxylase activity reflected the levels of cytochrome P-450a; 16 beta-hydroxylase activity the levels of cytochrome P-450b; and 2 alpha-hydroxylase activity the levels of cytochrome P-450h. It is concluded that the regio- and stereoselective hydroxylation of testosterone provides a functional basis to study simultaneously the regulation of several distinct isozymes of rat liver microsomal cytochrome P-450.
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We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 May 2011).
Food was withheld from foals overnight before intragastric administration of erythromycin estolate (25 mg/kg of body weight; n = 8) and erythromycin phosphate (25 mg/kg; 7). Four foals received both drugs with 2 weeks between treatments. Plasma erythromycin concentrations were determined at various times after drug administration by use of high-performance liquid chromatography. Maximum plasma peak concentrations, time to maximum concentrations, area under plasma concentration versus time curves, half-life of elimination, and mean residence times were determined from concentration versus time curves.
The MIC and MPC were determined for 191 penicillin/macrolide-susceptible clinical isolates of S. pneumoniae with azithromycin, clarithromycin and erythromycin using agar plate assays.
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The pharmacokinetics of erythromycin estolate (500 mg) and erythromycin ethylsuccinate (600 mg) were compared in 12 healthy volunteers after single doses and after repeated oral doses (every 8 h). High-pressure liquid chromatography with electrochemical detection was used to determine concentrations in plasma and urine of estolate, ethylsuccinate, and erythromycin base. The maximum concentration of drug in the serum, the half-life, and the area under the curve for erythromycin estolate were significantly greater than those of erythromycin ethylsuccinate after both regimens. After single and multiple doses, the respective areas under the curve of erythromycin base generated by estolate formulation were 3 and 1.6 times greater (P less than 0.05) than those of ethylsuccinate. The lower percentage of hydrolysis of erythromycin estolate (41 versus 69%) combined with its longer half-life (5.47 versus 2.72 h) and its larger area under the curve (30.61 versus 4.68 micrograms/h/ml, after multiple doses) could explain these differences. This study underscores the need for a specific high-pressure liquid chromatography assay and the importance of wide variability, rate-limited processes, changes with multiple doses, and the appearance of a second peak when one studies the pharmacokinetics of erythromycin esters. The pharmacokinetic data presented in this study reinforce the clinical advantages of erythromycin estolate over erythromycin ethylsuccinate.
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Three to four review authors independently extracted data and assessed the quality of each trial.