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Screening of anti-infectives against Leishmania donovani

Advances in Microbiology 2016年第1期6卷 13-22页

作者： Henry Nettey Grace Lovia Allotey-Babington Benoit Banga Nguessan Barima Afrane Mustafa Tagoe Anokye Ababio Patience Botchway Yvonne Darko Clement Sasu Alexander Nyarko School of Pharmacy University of Ghana Legon Ghana School of Pharmacy Mercer University Atlanta GA USA

Aim: To evaluate in vitro the effectiveness of several anti-infective agents alone and in combination against Leishmania donovani. Method: A convenient stratified sampling method was used to obtain selected anti-infective agents. For individual drug samples, Half Maximal Inhibitory Concentrations (IC50) were obtained using the broth dilution method. The IC50’s of the drugs which were active against L. donovani were used as reference values to prepare drug combinations for the modified microdilution checkerboard method. Results: Five (5) out of the fifty-six (56) drugs used showed activity (inhibition of cell growth) against L. donovani cells. They include Quinine sulphate (IC50 = 0.089 μg/ml), gentamicin (IC50 = 8.1 μg/ml), amodiaquine (IC50 = 138 μg/ml) and the two standard drugs: Amphotericin B (IC50 = 6.3 μg/ml) and Pentamidine (IC50 = 25 μg/ml). The remaining fifty-one (51) drugs did not show any inhibition within the range of concentrations used (1.25 - 160 μg/ml). The drug combinations of Pentamidine/Amodiaquine, Pentamidine/ Quinine sulphate, Pentamidine/Gentamicin, Amphotericin B/Quinine Sulphate, Amphotericin B/ Gentamicin, Amodiaquine/Quinine sulphate and Amodiaquine/Gentamicin showed synergistic effects against L. donovani whereas the Amphotericin B/Amodiaquine combination was antagonistic. Notable in the results obtained was the high effectiveness of quinine sulphate in inhibiting the growth of L. donovani. Quinine sulphate, though not indicated for leishmania treatment, was more effective than the two standard drugs and has a potential of playing a significant role in the treatment of leishmaniasis. Conclusion: This study has revealed five (5) anti-infective agents that by themselves or in combinations show activity against L. donovani. Some of the drug combinations which showed synergism should further be investigated. These results have to be confirmed by in vivo studies to d

关键词： anti-infectives Half Maximal Inhibitory Concentration Leishmania donovani

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Recovery rates of combination antibiotic therapy using in vitro microdialysis simulating in vivo conditions

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Journal of Pharmaceutical Analysis 2018年第6期8卷 407-412页

作者： Jayesh A.Dhanani Suzanne L.Parker Jeffrey Lipman Steven C.Wallis Jeremy Cohen John Fraser Adrian Barnett Michelle Chew Jason A.Roberts Burns Trauma and Critical Care Research Centre The University of Queensland UQ Centre for Clinical Research Department of Intensive Care Medicine Royal Brisbane & Women's Hospital Faculty of Health Queensland University of Technology Critical Care Research Group The University of Queensland Institute of Health and Biomedical Innovation & School of Public Health and Social Work Queensland University of Technology Department of Anaesthesiology and Intensive Care and Department of Medical and Health Sciences Link?ping University School of Pharmacy The University of Queensland Department of Pharmacy Royal Brisbane & Women's Hospital

Microdialysis is a technique used to measure the unbound antibiotic concentration in the interstitial spaces, the target site of action. In vitro recovery studies are essential to calibrating the microdialysis system for in vivo studies. The effect of a combination of antibiotics on recovery into microdialysate requires investigation. In vitro microdialysis recovery studies were conducted on a combination of vancomycin and tobramycin, in a simulated in vivo model. Comparison was made between recoveries for three different concentrations and three different perfusate flow rates. The overall relative recovery for vancomycin was lower than that of tobramycin. For tobramycin, a concentration of 20μg/mL and flow rate of 1.0μL/min had the best recovery. A concentration of 5.0μg/mL and flow rate of 1.0μL/min yielded maximal recovery for vancomycin. Large molecular size and higher protein binding resulted in lower relative recoveries for vancomycin. Perfusate flow rates and drug concentrations affected the relative recovery when a combination of vancomycin and tobramycin was tested. Low perfusate flow rates were associated with higher recovery rates. For combination antibiotic measurement which includes agents that are highly protein bound, in vitro studies performed prior to in vivo studies may ensure the reliable measurement of unbound concentrations.

关键词： Microdialysis Combination antibiotic therapy Relative recovery rate Pharmacokinetics anti-infectives Protein binding

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