Effect of Age on the Gastrointestinal Absorption of Acyclovir in Rats

Abstract

Drug elimination from the body after intravenous administration of acyclovir (20 mg kg-1) was delayed in 1-week-old rats but the pharmacokinetic data for 2.5-week-old rats were the same as those for 8-week-old rats. The areas under the plasma concentration-time curves at 0-infinity h (AUC) after oral administration of acyclovir (20 mg kg-1) decreased with increasing age. The absolute bioavailabilities for 1-, 2.5-, 3- and 8-week-old rats were 77.59, 51.52, 14.61 and 7.30%, respectively. The gastrointestinal absorption of poorly absorbed acyclovir was good for rats younger than 2.5 weeks but dropped abruptly between 2.5 and 3 weeks of age. The intestinal membrane permeability of acyclovir was studied using the everted sac method. The rate of transfer of an initial concentration of 10 microM acyclovir from the mucosal to the serosal side was constant until 60 min in rats of different ages while the rate in 2.5-week-old rats was significantly greater than that in 3-, 4- and 8-week-old rats. Abrupt in-vivo and in-vitro changes were observed in the experimental results between 2.5- and 3-week-old rats; this period coincided with the weaning period of the rat. The membrane transport mechanism of acyclovir in 2.5- and 8-week-old rats was also studied. Cumulative transferred amounts of acyclovir were linear (r = 0.99) over the range 5 microM-1 mM and dose-independent. The influence of metabolic inhibitors (sodium azide, 2,4-dinitrophenol, ouabain), purine and pyrimidine analogues (2-deoxyguanosine, guanine, adenine, uridine) and temperature on the permeation of acyclovir was studied. The permeation of acyclovir was inhibited only by 2-deoxyguanosine and guanine in 2.5-week-old rats. These results suggest that throughout the maturation period, the gastrointestinal absorption mechanism of acyclovir is predominantly via passive diffusion with little or no active or facilitated transport.(ABSTRACT TRUNCATED AT 250 WORDS)

Hydrophilic interaction liquid chromatography/electrospray mass spectrometry determination of acyclovir in pregnant rat plasma and tissues

“…This model is consistent with reported literature models for ACV kinetics in the rat 31. The volume of distribution at steady‐state was calculated to be 1.75 L/kg, also consistent with reported literature values 32. As expected, the curves for maternal plasma and placenta mirror each other due to the ‘blood‐rich’ nature of this tissue.…”

Effect of Cyclosporine A on the Gastrointestinal Absorption of Acyclovir in Neonatal and Adult Rats

“…There was a significant difference in the absorption by control and CyA-treated neonatal rats, but not for adult rats. One earlier report states that the bioavailability for 2.5-week-old rats was 3.5 times that for 3-weekold normal rats after administration of acyclovir [15]. Therefore, the difference of bioavailability between neonatal control and CyAtreated rats was attributable to the difference in gastrointestinal absorption based on the immaturity of intestinal development of CyAtreated rats and the difference in the elimination rate.…”

Lack of Effect of Aciclovir on Metabolism of Theophylline and Expression of Hepatic Cytochrome P450 1A2 in Rats

“…19,44) Fujioka et al 45) reported that the absolute bioavailability of aciclovir after oral administration of 20 mg/kg in Wistar rats was 7.3%. However, a study on the pharmacokinetics of aciclovir in subjects with end-stage renal disease showed that the bioavailability of aciclovir after intraperitoneal administration in patients receiving continuous ambulatory peritoneal dialysis was approximately 60%, suggesting that the peritoneal cavity is an alternative route for aciclovir administration in patients with poor vascular access.…”