Le tadalafil possède une affinité marquée pour la PDE5, mais épargne en grande partie les isoformes PDE1, PDE2 et PDE11, réduisant ainsi le risque d’effets extra-caverneux. L’action se traduit par une augmentation contrôlée de la circulation sanguine locale, indépendante des variations alimentaires. Sa pharmacocinétique repose sur une absorption digestive rapide, un métabolisme hépatique par CYP3A4 et une distribution tissulaire large. La biodisponibilité reste stable, et l’équilibre plasmatique est atteint en quelques jours lors d’administrations répétées. Les interactions cliniquement significatives surviennent avec les inhibiteurs puissants de CYP3A4 tels que le kétoconazole. Dans la littérature pharmacologique, acheter cialis 20 mg est souvent associé à des schémas d’utilisation basés sur la durée prolongée de son action.

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J. Physiol. Biochem., 57 (4), 343-344, 2001
Verapamil sensitisation to alkaloids on colchicine-selected
human colon adenocarcinoma cells
exposed to different drug doses for 1 hour (MDR), the main cause of failure in cancer until colony formation. The effect of ver- extrusion of the antineoplastic drugs from apamil as a drug sensitiser was performed by the exposure of colon cells to different that acts as an extracting pump (2). There- multidrug resistance associated with P-gly used to assess the normal distribution of the data. Additional statistical analyses caused by this protein. Verapamil reverses were made with the student’s t-test. A sig- drug resistance by competitively inhibit- ing the binding of P-gly and the cytotoxic drugs, allowing for the drug to accumulate on the sensitisation of the selected cell The aim of this study is to investigate if loids. In all cases, the surviving fraction a multidrug resistant colon carcinoma cell line that has been selected with colchicine added together with the drug. The highest for verapamil increased sensitivity to 0.5 selection. Verapamil increased sensitivity 2/1cch), selected from the parental line (6) drugs. The present results are similar to findings (3) reporting that verapamil (1-5 6RADR cell lines. While other authors (4) 10 µg/ml of verapamil in KB-C1 cells.
PIRKER et al. (7) have demonstrated that 5 antineoplastic drug activity and verapamil µg/ml verapamil is sufficient to complete- ly reverse the resistance to CCH in these exponentially growing culture in drug free cells. Therefore, it appears that a vera- cient to produce a significant sensitising M.J. RUIZ GÓMEZ, A. SOUVIRON, L. GIL AND M. MARTÍNEZ MORILLO Table I. Different sensitisation levels by verapamil on human colon adenocarcinoma cells (HCA-2/1cch) Data represent mean surviving fraction ± SD of three independent experiments in triplicate. *p<0.05;**p<0.01; ***p<0.005; ****p<0.001; (Student’s t-test).
effect for the majority of cell lines (11), 4. Goodman, G. E., Yen, Y. P., Cox, T. C., et al. (1987): Cancer Res., 47, 2295-2304.
with our findings reported that verapamil 5. Macfarlane, D. E. and Manzel, L. (1998): J.
Immunol., 160, 1122-1131.
(10 µg/ml) did not sensitise the multidrug 6. Morales, J. A., Ruiz-Gómez, M. J., Gil-Car- mona, L., et al. (1995): Rev. esp. Fisiol., 51, 43-
7. Pirker, R., Keilhauer, G., Raschack, M., et al.
(1990): Int. J. Cancer, 45, 916-919.
8. Ruiz Gómez, M. J., Gil, L., Souviron, A. et al. (2000): J. Physiol. Biochem., 56, 33-38.
9. Ruiz Gómez, M. J., Pastor Vega, J. M., de la Peña, L., et al. (1999): J. Physiol. Biochem., 55,
79-84.
10. Twentyman, P. R., Reeve, J. G., Koch, G., et al. (1990): Br. J. Cancer, 62, 89-95.
11. Woodcock, B. G., Abdel-Rahman, M. S., References
Wosch, F., et al. (1993): Eur. J. Cancer, 29, 559-
561.
1. Bowles, A. P., Pantazis, C. G. and Wansley, W.
(1990): J. Neurosurg., 73, 248-253.
Key words: Alkaloid, Colon carcinoma, Multidrug
2. Brian, L. J., Dalton, W., Fisher, G. A., et al. resistance (MDR), P-glycoprotein, Sensitisation, (1993): Cancer, 72, 3484-3488.
3. Cano-Gauci, D. F. and Riordan, J. R. (1987): Biochem. Pharmacol., 36, 2115-2123.
M. J. Ruiz Gómez, A. Souviron, L. Gil and
M. Martínez Morillo
Correspondence to M. Martínez Morillo (Tel.: +34 Departamento de Radiología y Medicina Física, 952 131 631; Fax: +34 952 131630; e-mail: mmorillo@ Facultad de Medicina, Universidad de Málaga, J. Physiol. Biochem., 57 (4), 2001

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