Bioanalytical method development, pharmacokinetics, and toxicity studies of paromomycin and paromomycin loaded in albumin microspheres. Issue 6 (22nd March 2012)

• Record Type: Journal Article
• Authors: Khan, Wahid; Sharma, Shyam S.; Kumar, Neeraj
• Is Part Of: Drug testing and analysis. Volume 5:Issue 6(2013:Jun.)
• Page Start: 453
• Page End: 460
• Publication Date: 2012-03-22
• Subjects: Drugs -- Analysis -- Periodicals; Drug testing -- Periodicals; Chemistry, Forensic -- Periodicals; 615.1901
• DOI: 10.1002/dta.339
• Languages: English
• ISSNs: 1942-7603

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>Intracellular location of leishmania parasite in macrophages protects them from both hosts defence system as well as from antibiotics like paromomycin (PM) acting against them, thus there is a need of a formulation targeting intracellular parasites. Considering this, PM‐loaded albumin microspheres (PM‐MS) were prepared to target PM to macrophages where leishmania parasites resides and evaluated for their safety profile. A new bioanalytical method for quantitative determination of PM in rat plasma was developed by pre‐column derivatization with 9‐fluorenylmethyl chloroformate. The developed bioanalytical method was validated and applied for pharmacokinetic studies of PM administered by intramuscular and intravenous routes as well as for developed PM‐MS which were administered by intravenous route. Comparative acute and subacute toxicity studies were also carried out for these formulations. The developed method was found to be very sensitive with a quantification limit of 40 ng/ml. Pharmacokinetic studies demonstrated nearly 80% reduction in C<sub>max</sub> of PM when administered as PM‐MS, compared to other formulations at equivalent dose. Toxicity studies indicated increased level of blood urea and blood urea nitrogen in PM intramuscular injection at 90 mg/kg dose, whereas at the same dose level PM‐MS showed no symptoms of toxicity. Results obtained suggest that developed PM‐MS formulation is a promising alternative to the presently marketed PM intramuscular injection for the treatment of visceral leishmaniasis. Copyright © 2012 John Wiley & Sons, Ltd.</p> </abstract>