Interaction of alkyl/aryl-phosphonocarboylates and diphosphonates with different transport systems in the proximal renal tubule1-a
| Ki | ||||
|---|---|---|---|---|
| cl,PAH | cl,SO4−− | cl,succinate | l,Pi | |
| Alkyl/aryl-phosphonates | ||||
| Chlorofluoromethylphosphonate (shibe) | NS > 10 | 5.6 ± 4.1 | 9.7 ± 4.5 | |
| Ethylphosphonate (hoe) | NS > 10 | NS > 10 | NS > 20 | NS > 30 |
| Phenylphosphonate (ald) | 5.4 ± 2.8 | NS > 10 | NS > 20 | 29.3 ± 3.6 |
| 2-Hydroxy-5-nitrobenzylphosphonate (bu) | 0.9 ± 0.2 | 2.9 ± 1.6 | 14.4 ± 3.6 | |
| 2-Naphthylmethylphosphonate (bu) | 0.8 ± 0.2 | 0.5 ± 0.4 | 19.1 ± 9.8 | |
| 2-Naphthylhydroxymethylphosphonate (bu) | 1.3 ± 0.5 | 3.2 ± 1.8 | 4.7 ± 1.3 | |
| 2-Naphthyldifluoromethylphosphonate (bu) | 4.4 ± 2.6 | 0.35 ± 0.2 | 5.1 ± 1.8 | |
| Phosphonocarboxylates | ||||
| Phosphonoformate (foscarnet) (sig) | NS > 10 | NS > 10 | NS > 20 | 0.42 ± 0.17 |
| Phosphonoacetate (sig) | NS > 10 | 3.7 ± 2.0 | NS > 20 | 3.5 ± 1.6 |
| 2-Phosphonobutyrate (lan) | NS > 10 | NS > 10 | NS > 20 | 9.4 ± 4.5 |
| 3-Phosphonopropionate (shibe) | NS > 10 | NS > 10 | 4.2 ± 5.2 | NS > 30 |
| 4-Phosphonobutyrate (lan) | 0.9 ± 0.3 | NS > 10 | 7.0 ± 9.1 | NS > 30 |
| 4-Phosphono-2-hydroxybutyrate (shibe) | NS > 10 | NS > 20 | 28.4 ± 14.8 | |
| Diphosphonates | ||||
| Methanediphosphonate (hoe) | NS > 10 | NS > 10 | NS > 20 | 7.3 ± 3.5 |
| Etidronate (proga) | NS > 10 | 3.1 ± 1.9 | NS > 20 | 0.66 ± 0.37 |
| Clodronate (boe) | NS > 10 | 1.5 ± 0.6 | NS > 20 | 0.71 ± 0.48 |
| Pamidronate (ci) | NS > 10 | 7.2 ± 3.8 | NS > 20 | 2.2 ± 0.83 |
| Alendronate (msd) | NS > 10 | 9.9 ± 8.5 | NS > 20 | 1.6 ± 0.43 |
| Aminomethanediphosphonate (hoe) | NS > 10 | NS > 10 | NS > 20 | 5.8 ± 4.2 |
| N-Cyclohexylaminomethanediphosphonate (hoe) | NS > 10 | NS > 10 | NS > 20 | 5.3 ± 3.8 |
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↵1-a Values of app.Ki,cl,PAH, app.Ki,cl,SO4−−, app.Ki,cl,succinate, and app.Ki,l,Pi are presented in millimoles per liter.
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Each app.Ki value is calculated from at least seven test and seven alternatingly taken control micropuncture samples of three rats. Sources of the tested compounds are: ald, Sigma-Aldrich, Deisenhofen, Germany, boe, Boehringer, Mannheim, Germany; bu, Dr. T. R. Burke, Laboratory of Medicinal Chemistry, National Institutes of Health, Bethesda, MD; ci, Ciba-Geigy, Basel; hoe, Dr. H.-J. Lang, Hoechst AG, Frankfurt; Ian Lancaster Mühlheim/Main; msd, MSD Sharp Dohme, Haar, Germany; proga, Procter & Gamble Pharmac. Cincinnati, OH; shibe, Dr. S. Shirazi-Beechy, University of Wales, Aberystwyth, Dyfed, UK; sig, Sigma-Adrich, Deisenhofen, Germany.