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

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Serval ID
serval:BIB_6F38035F9E09
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Intraocular penetration of penciclovir after oral administration of famciclovir: a population pharmacokinetic model.
Journal
Journal of Antimicrobial Chemotherapy
Author(s)
Schenkel F., Csajka C., Baglivo E., Kondo-Oestreicher M., Dayer P., Gex-Fabry M., Daali Y.
ISSN
1460-2091 (Electronic)
ISSN-L
0305-7453
Publication state
Published
Issued date
2013
Peer-reviewed
Oui
Volume
68
Number
7
Pages
1635-1641
Language
english
Notes
Publication types: Journal Article Publication Status: ppublish
Abstract
OBJECTIVES: We developed a population model that describes the ocular penetration and pharmacokinetics of penciclovir in human aqueous humour and plasma after oral administration of famciclovir.
METHODS: Fifty-three patients undergoing cataract surgery received a single oral dose of 500 mg of famciclovir prior to surgery. Concentrations of penciclovir in both plasma and aqueous humour were measured by HPLC with fluorescence detection. Concentrations in plasma and aqueous humour were fitted using a two-compartment model (NONMEM software). Inter-individual and intra-individual variabilities were quantified and the influence of demographics and physiopathological and environmental variables on penciclovir pharmacokinetics was explored.
RESULTS: Drug concentrations were fitted using a two-compartment, open model with first-order transfer rates between plasma and aqueous humour compartments. Among tested covariates, creatinine clearance, co-intake of angiotensin-converting enzyme inhibitors and body weight significantly influenced penciclovir pharmacokinetics. Plasma clearance was 22.8 ± 9.1 L/h and clearance from the aqueous humour was 8.2 × 10(-5) L/h. AUCs were 25.4 ± 10.2 and 6.6 ± 1.8 μg · h/mL in plasma and aqueous humour, respectively, yielding a penetration ratio of 0.28 ± 0.06. Simulated concentrations in the aqueous humour after administration of 500 mg of famciclovir three times daily were in the range of values required for 50% growth inhibition of non-resistant strains of the herpes zoster virus family.
CONCLUSIONS: Plasma and aqueous penciclovir concentrations showed significant variability that could only be partially explained by renal function, body weight and comedication. Concentrations in the aqueous humour were much lower than in plasma, suggesting that factors in the blood-aqueous humour barrier might prevent its ocular penetration or that redistribution occurs in other ocular compartments.
Pubmed
Web of science
Open Access
Yes
Create date
18/07/2013 18:41
Last modification date
25/09/2019 7:09
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