Creatinine kinetics in the rabbit

Journal of Pharmacokinetics and Biopharmaceutics - Tập 7 - Trang 291-301 - 2015
Mehdi Boroujerdi1, Albert M. Mattocks1
1School of Pharmacy, University of North Carolina, Chapel Hill

Tóm tắt

To evaluate the kinetics of creatinine in the rabbit, two radiotagged creatinine forms were used, with14C in the amidino group or with it in the carboxyl group. Five animals were injected intravenously with tracer amounts, and plasma samples were taken for 250–300 min; urine and feces samples were taken over longer periods. A chromatographic method was used to separate unchanged creatinine from other components of the samples prior to measurement for chemical and radioactivity content. Equations for the proposed flow model were derived and fitted to specific activity data, and values for transfer constants, production rates, and pool sizes were calculated. Evidence supported the concept that a two-compartment model is required and that production occurs in the peripheral compartment. Evidence also indicated that muscle represents a major part of the peripheral compartment. Small amounts of metabolites, chiefly guanido compounds, were detected when amidino-labeled creatinine was used. Also, small amounts of unchanged creatinine and metabolites were found in the feces.

Tài liệu tham khảo

R. Dominguez, H. Goldblatt, and E. Pomerene. Kinetics of the elimination of substances injected intravenously (experiments with creatinine).Am. J. Physiol. 114:240–254 (1935–1936). L. A. Sapirstein, D. G. Vidt, M. J. Mandel, and G. Hanusek. Volume of distribution and clearances of intravenously injected creatinine in the dog.Am. J. Physiol. 181:330–336 (1955). J. Greenberg, I. L. Schwartz, M. Spinner, L. Silver, and N. Starr. Apparent volumes of distribution ofp-aminohippurate and creatinine in the dog.Am. J. Physiol. 168:86–92 (1952). H. Favre and R. Beauwens. L'analyse compartimentale du metabolisme de la créatinine.Schweiz. Med. Wsch. 104:1182–1187 (1974). W. L. Chiou and H. H. Fung. Pharmacokinetics of creatinine in man and its implication in the monitoring of renal function and in dosage regimen modifications in patients with renal insufficiency.J. Clin. Pharmacol. 15:427–434 (1975). K. Bloch and R. Schoenheimer. Studies in protein metabolism. XI. The metabolic relation of creatine and creatinine studied with isotopic nitrogen.J. Biol. Chem. 131:111–119 (1939). G. Perez, A. Rey, M. Micklus, and I. Stein. Cation-exchange chromatography of guanidine derivatives in plasma of patients with chronic renal failure.Clin. Chem. 22:240–242 (1976). J. D. Jones and P. C. Burnett. Creatinine metabolism in humans with decreased renal function: Creatinine deficit.Clin. Chem. 20:1204–1212 (1974). R. Shainkin, Y. Fiatt, and G. M. Berlyne. The presence and toxicity of guanidinopropionic acid in uremia.Kidney Int. 7:S-302–S-305 (1975). M. J. Micklus and I. M. Stein. The colorimetric determination of mono and disubstituted guanidines.Anal. Biochem. 54:545–553 (1973). M. Boroujerdi. Kinetics and metabolism of creatinine. Ph.D. dissertation. University of North Carolina, Chapel Hill, N.C., 1978, pp. 123–139. A. J. Sedman and J. G. Wagner.Manual for AUTOAN (a decision-making pharmacokinetic computer program), Upjohn Center for Clinical Pharmacology, Ann Arbor, Mich., 1974. A. Rescigno and G. Segre.Drug and Tracer Kinetics, Blaisdell, Waltham, Mass., 1966, pp. 45–53. C. M. Metzler.A User's Manual for NONLIN and Associated Programs, Upjohn Co., Kalamazoo, Mich., 1976. D. Perrier and M. Gibaldi. Estimation of drug elimination in renal failure.J. Clin. Pharmacol. 13:458–462 (1973). A. White, P. Handler, and E. L. Smith.Principles of Biochemistry, McGraw-Hill, New York, 1964, 739. R. W. Lippman. Endogenous and exogenous creatinine clearance in the rat.Am. J. Physiol. 12:211–214 (1947). J. Kampmann, K. Siersback-Nielsen, M. Kristensen, and J. M. Hansen. Rapid evaluation of creatinine clearance.Acta Med. Scand. 196:517–520 (1974). B. I. Kaplan and H. W. Smith. Excretion of inulin, creatinine, xylose and urea in the normal rabbit.Am. J. Physiol. 113:354–360 (1935). P. D. Doolan, E. L. Alpen, and G. B. Theil. A clinical appraisal of the plasma concentration and endogenous clearance of creatinine.Am. J. Med. 32:65–79 (1962). A. Hunter.Creatine and Creatinine, Longmans Green, New York, 1928, pp. 78–79.