ArticlePharmaceutical research2003
Cell handling, membrane-binding properties, and membrane-penetration modeling approaches of pivampicillin and phthalimidomethylampicillin, two basic esters of ampicillin, in comparison with chloroquine and azithromycin.
Article in Pharmaceutical research, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 16 citations in OpenAlex.
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- Synergy of Tumor Microenvironment Remodeling and Autophagy Inhibition to Sensitize Radiation for Bladder Cancer Treatment.Theranostics · 2020Article
- Quantification of the anti-influenza drug zanamivir in plasma using high-throughput HILIC-MS/MS.Bioanalysis · 2011Article
- Cells on pores: a simulation-driven analysis of transcellular small molecule transport.Molecular pharmaceutics · 2010Article
- Influence of efflux transporters on the accumulation and efflux of four quinolones (ciprofloxacin, levofloxacin, garenoxacin, and moxifloxacin) in J774 macrophages.Antimicrobial agents and chemotherapy · 2005Article
- Accumulation and oriented transport of ampicillin in Caco-2 cells from its pivaloyloxymethylester prodrug, pivampicillin.Antimicrobial agents and chemotherapy · 2005Article
- Cellular pharmacokinetics and pharmacodynamics of the glycopeptide antibiotic oritavancin (LY333328) in a model of J774 mouse macrophages.Antimicrobial agents and chemotherapy · 2004Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeThe purpose of this work was to examine and understand the cellular pharmacokinetics of two basic esters of ampicillin, pivaloyloxymethyl (PIVA) and phthalimidomethyl (PIMA), in comparison with lysosomotropic drugs (chloroquine, azithromycin).
methodsCell culture studies (J774 macrophages) were undertaken to study uptake and release kinetics and to assess the influence of concentration, pH, proton ionophore (monensin), and MRP and P-gp inhibitors (probenecid, gemfibrozil, cyclosporin A, GF 120918). Equilibrium dialysis with liposomes were performed to directly asses the extent of drug binding to bilayers. Conformational analysis modeling of the drug penetration in bilayers was conducted to rationalize the experimental observations.
resultsPIVA and PIMA showed properties in almost complete contrast with those of chloroquine and azithromycin, i.e., fast apparent accumulation and fast release at 4 degrees C as well as at 37 degrees C, saturation of uptake (apparent Kd 40 microM), no influence of monensin, MRP, or P-gp inhibitors; tight binding to liposomes (Kd approx. 40 microM); and sharp increase in calculated free energy when forced in the hydrophobic domain.
conclusionsAlthough they are weak organic bases, PIVA and PIMA show none of the properties of lysosomotropic agents. We hypothesize that they remain locked onto the pericellular membrane and may never penetrate cells as such in significant amounts.
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