Effect of cyclosporine A on the gastrointestinal absorption of acyclovir in neonatal and adult rats.
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.
Mizuno
N
N
School of Pharmaceutical Sciences, Mukogawa Women's University, Nishinomiya, Hyogo, Japan. nmizuno@mwu.mukogawa-u.ac.jp
Takagi
C
C
Yamamoto
N
N
Takahashi
K
K
D000212:Acyclovir / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000375:Aging; D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development / Q000502:physiology*; D000998:Antiviral Agents / Q000493:pharmacokinetics; D001682:Biological Availability; D016572:Cyclosporine / Q000009:adverse effects / Q000494:pharmacology*; D004064:Digestive System / Q000254:growth & development*; D004347:Drug Interactions; D005260:Female; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000494:pharmacology*; D066298:In Vitro Techniques; D007408:Intestinal Absorption / Q000187:drug effects*; D007421:Intestine, Small / Q000187:drug effects / Q000254:growth & development; D007668:Kidney / Q000187:drug effects / Q000254:growth & development; D007700:Kinetics; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D015430:Weight Gain
D000998:Antiviral Agents; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D000212:Acyclovir