Changes in Rosuvastatin Pharmacokinetics During Postnatal Ontogenesis in Rats

• Published in: Journal of pharmacy & pharmaceutical sciences Vol. 25; pp. 1 - 8
• Main Authors: Roušarová, Jaroslava, Šíma, Martin, Kozlík, Petr, Křížek, Tomáš, Slanař, Ondřej
• Format: Journal Article
• Language: English
• Published: Canada Frontiers Media S.A 23.12.2021
• Subjects: Animals; Animals, Newborn; Area Under Curve; Dose-Response Relationship, Drug; Metabolic Clearance Rate; Rats; Rosuvastatin Calcium - pharmacokinetics; Sexual Maturation
• ISSN: 1482-1826; 1482-1826
• DOI: 10.18433/jpps32342

Statin therapy should be considered in children with familial hypercholesterolemia and sustained high LDL-C levels. There are no data on rosuvastatin exposure in patients <6 years and efficacy/safety can only be derived from case reports. Our aim was to examine developmental changes in pharmacokinetics of rosuvastatin in rats in vivo as a basis for clinical development of formulations for patients < 6 years. Rosuvastatin pharmacokinetics was examined in rats aged 1, 4, 7, 10, 14, 21, 28, 35 and 42 days (from birth to sexual maturity). After intraperitoneal dose of 5 mg/kg, blood samples to determine serum rosuvastatin levels were taken at 0.5, 3 and 5 hours. Pharmacokinetic parameters (Vd, CL, AUClast, AUC0-∞) were calculated using pharmacokinecic simulations. Both rosuvastatin CL and Vd started to increase systematically between 2 - 3 weeks of age, which was reflected by decreased total drug exposure. The AUC was up to 13 times higher in the age groups ≤14 days compared with the value at 42 days. Based on interspecies scaling, a dose reduction could be a feasible way, how to develop appropriate dosing schedule and formulations for children aged 2 - 6 years. However, confirmation in clinical development studies will be needed.