Abstract
The present study was aimed to evaluate neurotoxic effects of oseltamivir phosphate in lactating pups of orally dosed mice mothers during lactation. Twelve recently parturited female albino mice were divided equally into three groups, one control and two treated groups, each group consists of 4 dosed dams and 8 chosen pups .The nursing dams of T1 and T2 dosed daily orally with 1mg/kg and 5mg/kg,oseltamivir phosphate respectively representing the therapeutic dose and 5 fold dose of drug while control group dosed with distilled water. Lactating mice pups of all groups examined for the following parameters: First parameter was body weight changes and gain: In which T1group showed significant increase in mice pups body weight gain after 14 day of treatment in comparison with control group and T2. Second parameter was clinical symptoms observation /daily, all treatment groups that showed neurotoxic symptoms appeared from 1st dose and extended along the next few days of treatment to be gradually disappeared and completely lost within the last days of treatment in dose dependent manner.These neurotoxic symptoms were weakness, convulsions ,lay on back or side, extended body, incoordination ,extended limbs and limbs stiffness. Third parameter was gross and histopathological studies which demonstrate that the brain was the most affected organ beside extensive lesions in liver, kidney, stomach and small intestine of treated groups in dose dependent manner.In conclusion of this study revealed that Oseltamivir phosphate produce neurotoxic effect in mice pups through indirect administration by nursing mothers dosing during lactation period and the level of toxicity was in dose dependent manner.
Highlights
Oseltamivir phosphate (OP) is an orally administered anti-influenza agent of the neuraminidase inhibitor class
In conclusion of this study revealed that Oseltamivir phosphate produce neurotoxic effect in mice pups through indirect administration by nursing mothers dosing during lactation period and the level of toxicity was in dose dependent manner
No causative association could be demonstrated, and similar events were reported in the absence of oseltamivir (6 and 7)
Summary
Oseltamivir phosphate (OP) is an orally administered anti-influenza agent of the neuraminidase inhibitor class. The ethyl ester prodrug oseltamivir is administrated orally as a phosphate salt and converted by hepatic esterases to the active metabolite oseltamivir carboxylate (OC) (1). OC binds and inhibits the influenza virus neuraminidase enzyme that is essential for viral replication (2). In this way, oseltamivir limits the spread of influenza virus subtypes A and B within the infected host. Oseltamivir reduces the severity and duration of symptoms (3), while prophylactic administration prevents their onset (4). Abnormal or delirious behaviors have been reported with a low incidence in young individuals with influenza who were receiving oseltamivir (5). No causative association could be demonstrated, and similar events were reported in the absence of oseltamivir (6 and 7)
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