English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

The limited oral absorption in rodents of the antiherpesvirus agent 9-(4-hydroxy-3-hydroxymethylbut-l-yl)guanine (BRL 39123 [penciclovir; British approved name]) prompted a search for oral prodrugs. The 6-deoxy derivative of penciclovir (BRL 42359) and the corresponding diacetyl and dipropionyl 6-deoxy derivatives (BRL 42810 [famciclovir; British approved name] and BRL 43599) were tested as oral prodrugs. The in vivo absorption (dose, 0.2 mmol/kg) and the conversion to the active compound, penciclovir, were determined in rats. Compared with the sodium salt of penciclovir given intravenously, the bioavailabilities of penciclovir from orally administered penciclovir, BRL 42359, famciclovir, and BRL 43599 were 1.5, 9, 41, and 27%, respectively. These prodrugs and 6-deoxyacyclovir were tested for stability in rat duodenal contents and for metabolism in rat intestinal wall homogenate, liver homogenate, and blood and in the corresponding human fluids and tissues. Famciclovir was much more stable than BRL 43599 in human duodenal contents (half-lives, greater than 2 h and 7 min, respectively) yet was efficiently converted to penciclovir by the tissue homogenates. The major metabolic pathway was by deacetylation followed by oxidation at the 6 position. The rate of oxidation was comparable to that of 6-deoxyacyclovir, which is known to be converted efficiently to acyclovir in humans. Famciclovir was selected for further evaluation and progression to studies in humans. These subsequent studies confirmed that, after oral dosing with famciclovir, more than half the dose was absorbed and rapidly converted to penciclovir.

antimicrobial agents and chemotherapy

Selection of an oral prodrug (BRL 42810; famciclovir) for the antiherpesvirus agent BRL 39123 [9-(4-hydroxy-3-hydroxymethylbut-l-yl)guanine; penciclovir]