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  • Title: Effect of cyclosporine A on the gastrointestinal absorption of acyclovir in neonatal and adult rats.
    Author: Mizuno N, Takagi C, Yamamoto N, Takahashi K.
    Journal: Biol Neonate; 1998; 74(3):243-52. PubMed ID: 9691165.
    Abstract:
    The effect of cyclosporine A (CyA) on the pharmacokinetics of acyclovir in neonatal and adult rats was studied. CyA at 25 and 50 mg/kg for 2-week-old and adult rats, respectively, given as a subcutaneous injection, reduced growth of the 2-week-old rats and inhibited growth of adult rats. The plasma concentration of acyclovir after intravenous administration (20 mg/kg) to neonatal CyA-treated rats increased and the total body clearance decreased compared with the neonatal controls. The bioavailabilities of acyclovir for neonatal control and CyA-treated rats after oral administration were significantly different at 15.6 and 22.0%, respectively, but those for the adult control and CyA-treated rats were the same at 15.6 and 14.0%, respectively. Experiments using the everted sac method showed that the amount of acyclovir transferred was higher in neonatal CyA-treated rats than the controls, but there was no difference in adult rats. A good relationship was observed between the bioavailabilities (in vivo) and cumulative transferred amounts (in vitro) in CyA-treated and control rats. Lactase activity in the brush border membrane of the intestine in the neonatal CyA-treated rats was significantly higher than in the controls. These results suggest that the gastrointestinal maturation of CyA-treated neonates is suppressed, resulting in increased bioavailability of acyclovir, while the gastrointestinal absorption of acyclovir does not differ between adult CyA-treated and control rats.
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