Summary
Four subjects received 5 mg14C-glipizide orally and3 subjects1 mg intravenously. The average absorption of the oral dose was nearly 100% with peak plasma levels occurring between 90 and 360 min. The apparent half-life of plasma radioactivity was approximatively 3.7 h, the disappearance of radioactivity following complex kinetics due to metabolism of the drug. Extraction with CH2Cl2 and chromatography showed that in plasma 85% of the total radioactivity corresponded to unchanged glipizide, but in urine 98% to more polar and more readily excreted metabolites. The urinary excretion is 68% of the dose. The hypoglycaemic effect of glipizide is comparable to glibenclamide. The administration of14C-glipizide to two patients with renal insufficiency showed that the metabolism of the drug is independent of kidney function, that the rate of disappearance of the unchanged glipizide was approximately the same as in normals, but that the “halflife” of the metabolites was increased to 20 h and more.
Article PDF
Similar content being viewed by others
References
Ambrogi, V., Bloch, K., Daturi, S., Griggi, P., Logemann, W., Mandeli, V., Parenti, M.A., Babini, T., Usardi, M.M., Tommasini, R.: Pharmacological study on a new antidiabetic: N-{4-[β-(5-methyl-pyrazine-2-carboxamido)-ethyl]-benzene-sulfonyl}-N′-cyclohexyl urea or K 4024. Arzneimittel-Forsch.21, 208–215 (1971)
Pedrazzi, F., Pisani Ceretti, A., Losi, S., Bommartini, F., Artini, D., Emanueli, A.: Evaluation in hospitalized subjects of a new hypoglycemic sulfonylurea, glydiazinamide. Arzneimittel-Forsch.21, 220–225 (1971)
Ambrogi, V., Artini, D., Fucella, L.M., Goldaniga, G., Orsini, G., Ronchi, R., Tamassia, V., Valzelli, G., Angelucci, R.: Farmacocinetica e metabolismo in animali da esperimento e nell'uomo della N-{4-[β-(5-metilpirazina-2-eorbossiamido)-etil]-benzensulfonil}-N′ cicloesil-urea (K 4024). Boll. chim. farm.111, 251–264 (1972)
Stowers, J.M., Constable, L.W., Hunter, B.B.: A clinical and pharmacological comparison of chlorpropamide and other sulfonylureas. Ann. N. Y. Acad. Sci.74, 689–695 (1959)
Ueda, H., Sakurai, T., Ota, M., Nakajima, A., Kamii, K., Maezawa, H.: Disappearance rate of tolbutamide in normal subjects and in diabetes mellitus, liver cirrhosis and renal disease. Diabetes12, 414–419 (1963)
Cohen, B.D., Galloway, J.A., McMahon, R.E., Root, M.A., Henriques, K.J.: Carbohydrate metabolism in uremia: blood glucose response to sulfonylurea. Amer. J. med. Sci.254, 608–618 (1967)
Petitpierre, B., Fabre, J.: Effet de l'insuffisance rénale sur l'action hypoglycémiante des sulfonylurées. Schweiz. med. Wschr.102, 570–578 (1972)
Dubach, U.C., Bückert, A., Forgo, I., Rentsch, G.: Etude pharmaco-clinique du glibornuride. Symposium international sur les agents hypoglycémiants. Evian 1971
Zender, R.: Une microméthode automatique pour l'analyse quantitative des aldohexoses dans les liquides biologiques par l'o-toluidine. Clin. chim. Acta8, 351–358 (1963)
Hales, C.N., Randle, P.Y.: Immunoassay of insulin with insulin-antibody precipitate. Biochem. J.88, 137–146 (1963)
Catt, K., Tregear, G.W.: Solid-phase radioimmunoassay in antibody-coated tubes. Science158, 1570–1572, (1967)
Hodges, P.: Personal communication
Valzelli, G.: Personal communication
Bray, G.A.: A simple efficient liquid scintillaton for counting aqueous solutions in a liquid scintillation counter. Analyt. Biochem.1, 279–285 (1960)
Heptner, W., Kellner, H.-M., Christ, O., Weihracen, D.: Metabolismus von HB 419 am Tier. Arzneimiuel-Forsch.19, 1400–1404 (1969)
Zahnd, G., Balant, L., Fabre, J.: In preparation
Anderson, J., Stephenson, B.J., Tomlinson, R.W.S., Weinberg, A.L.: Studies with 14C-labelled glib nclamide. Postgrad. med. J. Dec. Suppl. 42–45 (190)
Gibaldi, M.: Pharmacokinetic aspects of drug metabolism. Ann. N.Y. Acad. Sci.179, 19–31 (1971)
Rupp, W., Christ, O., Heptner, W.: Resorption, Aus-Scheidung und Metabolismus nach intravenöser und oraler Gabe von HB 419 an Menschen. Arzneimitten-Forsch.19, 1428–1434 (1969)
Carlo Erba: Personal communication
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Balant, L., Zahnd, G., Gorgia, A. et al. Pharmacokinetics of glipizide in man: Influence of renal insufficiency. Diabetologia 9 (Suppl 1), 331–338 (1973). https://doi.org/10.1007/BF01218443
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01218443