Abstract
Background: Oseltamivir is an antiviral drug widely used for the treatment and prevention of influenza A and B infections. Following oral administration, oseltamivir phosphate is converted to its active metabolite, oseltamivir carboxylate. Both oseltamivir and its active metabolite can cross the placenta, highlighting the importance of evaluating their potential effects during pregnancy and on developing offspring.
Objective: This study aimed to evaluate the developmental, reproductive, and cytogenetic effects of oseltamivir in pregnant mice, their fetuses, and pups following exposure to therapeutic and ten-fold doses during different stages of pregnancy.
Methods: Seventy pregnant mice were equally divided into control and three treatment groups corresponding to the three stages of pregnancy. Each treatment group was further divided into therapeutic-dose and overdose groups. Oseltamivir phosphate was administered orally at 2 mg/kg body weight (therapeutic dose) and 20 mg/kg body weight (ten-fold dose) daily during the corresponding stage of pregnancy. Prenatal, postnatal, reproductive, and cytogenetic parameters were subsequently evaluated.
Results: Oseltamivir exposure resulted in a significant increase in dead and resorbed fetuses, accompanied by significant decreases in gestation period, gestation index, and fertility index. Postnatal assessment demonstrated significant decreases in viability index, lactating index, and weight gain of suckling pups. Cytogenetic assessment showed a significant increase in mitotic index in male and female mice treated during the first stage of pregnancy at both doses. In pups, the mitotic index significantly increased following the overdose and decreased following the therapeutic dose.
Conclusion: Both therapeutic and ten-fold doses of oseltamivir produced significant prenatal and postnatal effects, with effects varying according to dose and stage of pregnancy. Prenatal effects were more prominent during the first and second stages, whereas postnatal effects were mainly observed following exposure during the second and third stages. Cytogenetic alterations were also observed, particularly among pups exposed to the ten-fold dose.
| Has the manuscript been published | published |
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| Intend to be published in the IJPS ? | NO |
