OPEN-ACCESS PEER-REVIEWED
1Nilesh Mahajan, 2Suchitra Mishra, 3Amol Warokar, 4Sachin More, 5Anil Pethe
1Dadasaheb Balpande College of Pharmacy, Besa, Nagpur, Maharashtra, India.
2Dadasaheb Balpande College of Pharmacy, Besa, Nagpur, Maharashtra, India.
3Dadasaheb Balpande College of Pharmacy, Besa, Nagpur, Maharashtra, India.
4Dadasaheb Balpande College of Pharmacy, Besa, Nagpur, Maharashtra, India.
5Datta Meghe College of Pharmacy, Wardha, Maharashtra, India.
Abstract
Background: Niclosamide (NIC) has been proposed as an interesting molecule for repurposing for antiviral activity. This study examined the comparative pharmacokinetic study of niclosamide by intranasal and intraperitoneal route in male Sprague-Dawley rats.
Material & Methods: The bioanalytical method was developed on Reverse Phase High Performance Liquid Chromatography (RP-HPLC) for estimation of niclosamide in the presence of ibuprofen as an internal standard. An isocratic elution of mobile phase of 20 mM phosphate buffer; pH 4.5: methanol (15: 85 % v/v) was maintained at flow rate of 1.1 mL/min and effluent was monitored by Photo Diode Array (PDA) detector at 254 nm.
Results: After a single 20 mg/kg intraperitoneal dose, the maximum concentration (Cmax) of niclosamide was found to be 9031±0.003 ng /ml, maximum time to reach peack concentration (tmax) was 2 hr and half-life (t1/2) of was found to be 0.55845±0.001 hours, whereas after intranasal administration the Cmax of niclosamide was found to be 6109±0.0026 ng /ml, t max was 5 hr and half-life (t1/2) was found to be 1.617186±0.0017 hr. The plasma peak concentration of niclosamide after two hours was 6.8 μg after 2 hr of intranasal administration and gradually decrease with time, whereas there were no significant concentration of NIC detected in lungs by intraperitoneal administration. Two-fold increase in area under curve (AUCO-t) and Mean residence time (MRT) with diminished clearance after administration of niclosamide via intranasal route in lungs.
Conclusion: Relatively higher concentration of niclosamide was estimated in lungs via intranasal while in plasma via intraperitoneal route of administration in rats. It is imperative to elucidate the pharmacokinetic characteristics of niclosamide in human subjects prior to its prospective application in individuals afflicted with SARS-CoV.
Keywords: Pharmacokinetics, Drug repurposing, Niclosamide, RP-HPLC, Intranasal Route of Administration, Mean residence time
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