Intraocular penetration of penciclovir after oral administration of famciclovir: a population pharmacokinetic model

Schenkel, F.; Csajka, Chantal; Baglivo, Edoardo; Kondo-Oestreicher, M; Dayer, P.; Gex‐Fabry, Marianne; Daali, Youssef

doi:10.1093/jac/dkt064

Cited by 5 publications

(1 citation statement)

References 24 publications

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“…The bioavailability of orally administered acyclovir is 15–30% [ 10 ], whilst it is 70–80% for penciclovir [ 11 ]. Studies of the binding properties of ACV and PNV as well as other drugs with serum albumin can provide a clue towards pharmacological properties of those drugs.…”

Section: Introductionmentioning

confidence: 99%

Biophysical and In Silico Studies of the Interaction between the Anti-Viral Agents Acyclovir and Penciclovir, and Human Serum Albumin

et al. 2017

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Acyclovir (ACV) and penciclovir (PNV) have been commonly used during the last few decades as potent antiviral agents, especially for the treatment of herpes virus infections. In the present research their binding properties with human serum albumin (HSA) were studied using different advanced spectroscopic and in-silico methods. The interactions between ACV/PNV and HSA at the three investigated temperatures revealed a static type of binding. Extraction of the thermodynamic parameters of the ACV-HSA and PNV-HSA systems from the measured spectrofluorimetric data demonstrated spontaneous interactions with an enthalpy change (∆H0) of −1.79 ± 0.29 and −4.47 ± 0.51 kJ·mol−1 for ACV and PNV, respectively. The entropy change (∆S0) of 79.40 ± 0.95 and 69.95 ± 1.69 J·mol−1·K−1 for ACV and PNV, respectively, hence supported a potential contribution of electrostatic binding forces to the ACV-HSA and PNV-HSA systems. Putative binding of ACV/PNV to HSA, using previously reported site markers, showed that ACV/PNV were bound to HSA within subdomains IIA and IIIA (Sudlow sites I and II). Further confirmation was obtained through molecular docking studies of ACV-HSA and PNV-HSA binding, which confirmed the binding site of ACV/PNV with the most stable configurations of ACV/PNV within the HSA. These ACV/PNV conformers were shown to have free energies of −25.61 and −22.01 kJ·mol−1 for ACV within the HSA sites I and II and −22.97 and −26.53 kJ·mol−1 for PNV in HSA sites I and II, with hydrogen bonding and electrostatic forces being the main binding forces in such conformers.

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Section: Introductionmentioning

confidence: 99%