Placental and breastmilk transfer of voriconazole to offspring from pregnant and lactating bottlenose dolphins (Tursiops truncatus)

Abstract

AbstractFungal pneumonia is a common disease in bottlenose dolphins (Tursiops truncatus), including pregnant and lactating ones. Voriconazole (VRCZ) is commonly used to treat respiratory fungal infections in this species; however, it is unknown whether VRCZ is transferred via the placenta and breastmilk and whether its usage is safe in pregnant and lactating dolphins. We measured VRCZ concentrations in breastmilk and dams’, umbilical cord, and calves’ plasma samples from four dam-calf dolphin pairs in the Port of Nagoya Public Aquarium, Japan, treated with or without VRCZ. Three pregnant and/or lactating dams were administered VRCZ (loading dose 1.5–2.3 mg/kg, for 3 days; maintenance dose 1.5–3.1 mg/kg, every 5–18 days), twice daily, orally, without side effects in dams or calves. VRCZ was detected in two dams’ umbilical cord plasma (0.14 and 2.35 μg/ml) and in one calf's plasma (0.18 μg/ml), collected immediately after birth. Further, VRCZ was detected in breastmilk samples (maximum 13.45 μg/ml) from three VRCZ-administered dams and in plasma from three calves (maximum 7.54 μg/ml) given or nursed from VRCZ-administered dams’ breastmilk. The calves’ plasma VRCZ concentrations varied, depending on the amount of breastmilk and food consumed. VRCZ concentrations were higher in breastmilk samples than in dams’ plasma. To our knowledge, this is the first report on placental and breastmilk VRCZ transfer to offspring in bottlenose dolphins. During VRCZ medication in pregnant and lactating bottlenose dolphins, it is crucial to monitor plasma VRCZ concentrations and any side effects in dams as well as in their calves.