title: Bioanalytical method development, pharmacokinetics, and toxicity studies of paromomycin and paromomycin loaded in albumin microspheres.
abstract: 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(max) 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.
authors.affiliation: Department of Pharmaceutics, National Institute of Pharmaceutical Education & Research (NIPER), S.A.S., Nagar, India.
authors.forename: Wahid
authors.initials: W
authors.lastname: Khan
authors.forename: Shyam S
authors.initials: SS
authors.lastname: Sharma
authors.forename: Neeraj
authors.initials: N
authors.lastname: Kumar
mesh_terms: D000418:Albumins / Q000737:chemistry; D000563:Amebicides / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics* / Q000633:toxicity*; D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004337:Drug Carriers / Q000737:chemistry; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D007668:Kidney / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D057230:Limit of Detection; D008297:Male; D010303:Paromomycin / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics* / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000418:Albumins; D000563:Amebicides; D004337:Drug Carriers; D010303:Paromomycin