Therapeutic drug monitoring of total and free mycophenolic acid (MPA) and limited sampling strategy for determination of MPA-AUC in paediatric renal transplant recipients
Nephrology, Dialysis and Transplantation
Drug excretion is a concerted action of kidney, liver and intestine dispose of such agents differently and intestines [1,2]. One ultimate goal of the study of depending on their relative lipophilicity. The agents membrane transport of drugs is to answer the question: with relatively low molecular weight and lipophilicity which factors determine the relative contribution of are predominantly excreted by the kidneys. With excretory organs to the total body clearance of various increasing
... weight of the agents, the small classes of drugs? intestine and, in particular, the liver, play a more Earlier studies on the excretory profiles of cationic dominant role in their overall excretion . Drug drugs, using 14 organic cations with increasing molecuinteractions on the biliary excretion of cationic lar weight and lipophilicity, revealed that liver, kidney P-glycoprotein (P-gp) substrates and other cationic drugs can be predicted on the basis of their relative lipophilicity . Abstracts 2 References 20. Ernest S, Bello-Reus E. P-glycoprotein functions and substrates: possible role of MDR 1 gene in the kidney. Kidney Int 1998; 1. Meijer DKF, Smit JW, Mü ller M. Hepatobiliary elimination of 53: 511-517 cationic drugs: the role of P-glycoproteins and other ATP-21. Lauterbach F. Intestinal permeation of organic bases and quadependent transporters. Adv Drug Deliv Rev 1997; 25: 159-200 ternary ammonium compounds. In: Csazky TZ, ed. Handbook 2. Oude Elferink RPJ, Meijer DKF, Kuipers F, Jansen PLM, of Experimental Pharmacology, Vol. 70/II. Pharmacology of Groen AK, Groothuis GMM. Hepatobiliary secretion of organic Intestinal Permeation. Springer Verlag, Berlin: 1984; 271-284 compounds; molecular mechanisms of membrane transport. 22. Mayer U, Wagenaar E, Beijnen JH, Smit JW, Meijer DKF, Van Biochim Biophys Acta 1995; 1241: 215-268 Asperen J, Borst P, Schinkel AH. Substantial excretion of 3. Neef C, Meijer DKF. Structure-pharmacokinetics relationship digoxin via the intestinal mucosa and prevention of long-term of quaternary ammonium compounds. Correlation of physicodigoxin accumulation in the brain by the mdr 1a P-glycoprotein. chemical and pharmacokinetic parameters. Nooijen WJ, Beijnen JH, Van DKF. Interactions between P-glycoprotein substrates and other Tellingen O. Limited oral bio-availability and active epithelial cationic drugs at the hepatic excretory level. Br J Pharmacol excretion of paclitaxel ( Taxol ) caused by P-glycoprotein in the 1998; 123: 361-370 intestine. Proc Natl Acad Sci USA 1996; 94: 2031-2035 5. Koepsell H. Organic cation transporters in intestine, kidney, 24. Meijer DKF, Jansen PLM, Groothuis GMM. Hepatobiliary liver and brain. Annu Rev Physiol 1998; 60: 243-266 disposition and targeting of drugs and genes. In: Bicher J, 6. Bossuyt X, Mü ller M, Hagenbuch B, Meier PJ. Polyspecific Benhamou J-P, McIntyre N, Rizzetto M, Rodes J, eds. Oxford drug and steroid clearance by an organic anion transporter of AUETC sst is the AUETC of one dosage interval t lycoside therapy: importance of the ratio of peak concentration to minimal inhibitory concentration. J Infect Dis 1987; 155: 93-99 4. Prins JM, Bü ller HR, Kuijper EJ, Tange RA, Speelman P. Once Correspondence and offprint requests to: Dr David Czock, Medizinische Universitätsklinik, Sektion Nephrologie, Robert-Koch-versus thrice-daily gentamicin in patients with serious infections.