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A stereospecific high-performance liquid chromatographic assay was developed for the quantitation of ketoconazole enantiomers (KTZ) in rat plasma. After protein precipitation of 100 microL plasma using acetonitrile, a wash step was performed using hexane. The supernatant was removed and KTZ enantiomers and amiodarone, the internal standard, were extracted using liquid-liquid extraction with tert-butyl methyl ether. After transfer and evaporation of the organic layer, the residue was reconstituted in mobile phase and injected into the HPLC through a chiral column. The mobile phase consisted of hexane:ethanol:2-propanol with diethyl amine, pumped at 1.5 mL/min. All components eluted within 18 min. KTZ enantiomers were baseline resolved and peaks were symmetrical in appearance with no interferences. Calibration curves were linear over the range 62.5-5000 ng/mL of enantiomer. The intraday and interday CV% assessments were

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AimTo assess knowledge, attitude and practice (KAP) of antimicrobial self-medication among a convenience sample of population in Alexandria, Egypt.MethodologyA descriptive cross-sectional study using a self-administrated semi-constructed questionnaire. A convenience sample of 359 participants was studied using appropriate consent. The questionnaire had four sections: demographics, KAP, professional medical knowledge and attitude of children caregivers toward antimicrobial self-medication. The questionnaire was initially constructed in English and then translated into its final Arabic version. The Arabic version was pilot-tested and face-validated. Descriptive and quantitative analysis were performed using SPSS (V.20.0).ResultsApproximately 64% (231) of the studied population used antibiotics without prescription in the past 12 months. This was significantly correlated with female gender and lack of knowledge. The main reason for self-medication was due to saving time and effort (109, 47%) followed by not preferring doctor visits (89, 39%). More than 60% of cases used amoxicillin-clavulanic acid. The main sources of antibiotics were leftovers from previously prescribed pharmaceuticals and those purchased from community pharmacies. 85 participants were young children caregivers of which 18 (21%) reported administering antibiotics to their children without consulting a physician. Out of 115 who claimed attaining medical background, only 30 (26%) managed to answer section 3 correctly with 23 of them reporting antibiotic self-medication.ConclusionThis study showed an increased tendency towards antibiotic self-medication among Alexandrian adults and children that was not significantly decreased in population with medical background. The reasons discussed within the study should be further addressed to decrease such practice.

The pharmacokinetics of desethylamiodarone (DEA), the active metabolite of amiodarone (AM), were studied in the rat after administration of AM or preformed metabolite. Rats received 10 mg/kg of either intravenous or oral AM HCl or DEA base. Blood samples were obtained via a surgically implanted jugular vein cannula. Plasma concentrations were measured by a validated LC/MS method. In all AM treated rats, AM plasma concentrations greatly exceeded those of the formed DEA. The fraction of AM converted to DEA after i.v. administration was 14%. Amiodarone had a significantly lower (approximately 50%) clearance than DEA, although the volume of distribution and terminal phase half-life did not differ significantly. The hepatic extraction ratio of DEA was 0.48, similar to that of AM (0.51). Oral AM demonstrated higher plasma AUC (5.6 fold) and higher C(max) (6.1 fold) than oral DEA and oral bioavailability of AM (46%) was greater than DEA (17%). The estimated fraction of the oral dose of AM converted to DEA was 4.5 fold higher than after i.v. administration, suggesting first-pass formation of DEA from AM. Amiodarone and DEA differed in their pharmacokinetic characteristics mostly due to a higher CL of DEA. With oral dosing, AM appeared to undergo significant presystemic first-pass metabolism within the intestinal tract.