ABSTRACT

Background: Sodium stibogluconate, sold under the brand name Pentostam® among others, is a medication used to treat Cutaneous leishmaniasis (CL).It is applied by intralesional (I.L.), intravenous (I.V.), or intramuscular (I.M.) injection. This practice causes great pain and systemic side effects and results in very low patients compliance. Objective: To develop and evaluate various Pentostam® topical formulations. To assess the pharmacokinetic properties (ADME) of Pentostam® and to evaluate the application of the formulations as an alternative therapy to the systemic use, to avoid the disadvantages of the latter. Methods: Different formulations of Pentostam® in hydrous wool fat (HWF) ointment, polyethylene glycol (PEG), aqueous cream (AC), and gel were prepared and tested clinically against CL. The formulations were compared with other conventional medications tried by clinicians in epidemic situations. Also, SwissADME web server were utilized to evaluate the pharmacokinetic properties of the formulated preparation. Results: The four preparations (dimethyl sulfoxide enhancing incorporated with the previous mentioned bases and Pentostam® ) showed the following cure rates at the sixth week: Hydrous wool fat ointment (42.5%), Polyethylene glycol ointment (63.6%), aqueous cream (79.6%) and gel (81.6%). compliance rates percentages were (60%), (80%, 78%),(94%), (92%) respectively. Form the ADME analysis it is demonstrated that Pentostam® is a highly hydrophilic compound with -5.3 LogP value, and having a high water solubility with -0.5 LogS value. This results confirmed the drawn conclusion that the aqueous cream and the hydrogel formulations shows the best cure rate with 72% and 75% respectively. From the Log Kp (skin permeation) value was found to be -13.72 cm/s which means that this drug has high skin permeation ability, that’s why when we add it to highly lipophilic bases, the drug was not able to permeate to the skin, which is clearly demonstrated with low cure rate with Hydrous wool fat ointment and Polyethylene glycol ointment Conclusions: The 2% Pentostam® and 0.5% DMSO in aqueous cream and gel bases were found to be the most efficacious clinically in comparison to the other bases and the conventional and non-conventional regimens currently were used during the epidemic outbreak of the disease. The efficacy was assessed by the detection of the absence of L.D bodies from the lesions. The comparative studies showed that Pentostam® topical formulations were only second in efficacy to systemic Pentostam® with the obvious advantages of overcoming the drawbacks of the latter. Keywords: Pharmacokinetic ADME, Pentostam® topical application, Pentostam® systemic application Dimethylsulfoxide
Publication date: 01/02/2022

https://ijbpas.com/pdf/2022/February/MS_IJBPAS_2022_5885.pdf

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https://doi.org/10.31032/IJBPAS/2022/11.2.5885