Human gastrointestinal absorption of acyclovir from tablet duodenal infusion and sipped solution.

Abstract

On two occasions at least 1 week apart, nine healthy male volunteers were administered in random order either 2 x 200 mg (1.8 mmol) acyclovir tablets or 400 mg of acyclovir in 500 ml of 5% dextrose solution which was infused at constant rate into the duodenum over 4 h. Six of the subjects subsequently sipped the same solution at the rate of 10.4 ml in each 5 min period for 4 h. Blood and urine were sampled over 24 h for each mode of administration. Acyclovir was assayed by radioimmunoassay. Mean areas under the plasma concentrationtime curves (AUCs) + s.d. for tablet (T), intraduodenal infusion (I) and sipping (S) were, respectively: T = 14.7 + 5.1; I = 24.6 + 5.1; S = 28.4 + 9.5 (n = 6) ,umol 1-1 h. AUCs for I and S were significantly greater than that for T (2P < 0.05). Mean apparent maximum plasma concentrations (Cmax) + s.d. were T = 3.8 + 1.5; I = 4.8 + 0.9; S = 5.1 + 1.5 ,umol 1-1. This trend to higher values for I and S was not significant. Mean apparent plasma disappearance half-lives (ttl2) + s.d. were respectively T = 2.3 + 0.4; I = 2.7 + 0.5; S = 3.0 ± 0.2 h, I being significantly greater than T (2P < 0.05), as was S greater than T (2P < 0.01). The mean 24 h urinary recovery + s.d. of acyclovir (n = 8) was T = 309 + 119 ,umol (17% of dose); I = 471 + 83 ,imol (26% of dose); S = 507 ± 180 ,umol (28% of dose). I > T (P < 0.01), S > T (P < 0.05). Acyclovir absorption is increased when contact time of a solution with the absorptive area of the human gut is increased as compared with absorption available from the tablet. This suggests capacity limited absorption.

Novel approaches on prodrug based drug design

“…Acyclovir was the first antiviral agent that possessed potent and selective viral inhibition [22]. Nevertheless, the aefficacy of cyclovir was limited due to poor oral bioavailability [23]. In patients, the approximate bioavailability was 20 to 25% after oral administration.…”

Species Differences in the Metabolism and Disposition of Antiviral Nucleoside Analogues: 1. Acyclovir

“…In addition, six of the subjects subsequently sipped the same solution over a period of 4 h. The mean AUC for intraduodenal infusion (109.2h J.Lg rnr') and sipping (126.1 h J.Lg mr") were significantly greater than after tablet administration (65.3h J.Lg rnl"), indicating higher absorption when contact time of solution with absorptive area of the intestine was increased (Lewis et et., 1986). In another pilot study the mean AUC after administration of 600 mg of ACV, given orally in divided doses at 4-h intervals to six volunteers, was nearly three-fold higher than after a single 600-mg dose (Brigden et aI., 1980).…”

A Selective Search for Biologically Active Bipartate Nucleoside Prodrugs I : Bi̇yoloji̇k Akti̇vi̇tesi̇ Olan İki̇ Kisimli Nükleosi̇t Prodrug'lari İçi̇n Seçi̇ci̇ Bi̇r Tarama I

“…Acyclovir was the first antiviral agent that possessed potent and selective viral inhibition (43). Nevertheless, acyclovir efficacy was limited due to poor oral bioavailability (44). In-patient, the approximate bioavailability was 20 to 25% after oral administration.…”