The combinational use of acyclovir (ACV) phosphonate esters and alpha(2)-interferon was shown to produce a synergistic effect on inhibition of HSV-1 replication in Vero cell cultures. Unlike other acyclovir phosphonate derivatives studied earlier, ACV H-phosphonate is not an ACV prodrug. On penetrating into the cells, it may be directly converted into ACV monophosphate escaping dephosphonylation-phosphorylation steps.
The kinetics of the content of His-Phe-Arg-Trp-Pro-Gly-Pro (ACTH (6-9)PGP) and its hydrolysis products in the blood and brain of rats in the case of intranasal administration and intravenous injection of tritiated ACTH(6-9)PGP was studied. The parameters of bioavailability of ACTH(6-9)PGP administered intranasally were higher, indicating certain prospects in the intranasal application in clinical practice. We also found that the factor that determines ACTH(6-9)PGP proteolysis in experiments both in vivo and in vitro is aminopeptidases. The main products of ACTH(6-9)PGP during its metabolism in rats are short peptides and amino acids.
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