Semi-mechanistic kidney model incorporating physiologically-relevant fluid reabsorption and transporter-mediated renal reabsorption: pharmacokinetics of γ-hydroxybutyric acid and l-lactate in rats

Journal of Pharmacokinetics and Pharmacodynamics

Volumn 42, Issue 5, 2015, Pages 497-513

  Dave, Rutwij A ^a   Morris, Marilyn E ^a  

^a UNIVERSITY AT BUFFALO   (United States)

Author keywords

l Lactate; Monocarboxylate transporters (MCTs); Physiologically relevant fluid reabsorption; Population pharmacokinetics; Semi mechanistic kidney model; Transporter mediated renal reabsorption; Hydroxybutyric acid (GHB)

Indexed keywords

4 HYDROXYBUTYRIC ACID; LACTIC ACID; MONOCARBOXYLATE TRANSPORTER; MONOCARBOXYLATE TRANSPORTER 1; SODIUM COUPLED MONOCARBOXYLATE TRANSPORTER 1; UNCLASSIFIED DRUG; 4-HYDROXYBUTYRIC ACID; CARRIER PROTEIN; HYDROXYBUTYRIC ACID;

ANIMAL EXPERIMENT; AREA UNDER THE CURVE; ARTICLE; BLOOD; DRUG METABOLISM; EXPERIMENTAL MODEL; HENLE LOOP; HUMAN; HUMAN CELL; KIDNEY; KIDNEY COLLECTING TUBULE; KIDNEY DISTAL TUBULE; KIDNEY PROXIMAL TUBULE; KIDNEY TUBULE ABSORPTION; LIVER; LIVER CELL; MALE; MATHEMATICAL ANALYSIS; NEPHRON; NONHUMAN; PRIORITY JOURNAL; RAT; RENAL CLEARANCE; SEMI MECHANISTIC KIDNEY MODEL; TRANSPORT KINETICS; VALIDITY; ANIMAL; BODY FLUID; DOSE RESPONSE; DRUG EFFECTS; INTRAVENOUS DRUG ADMINISTRATION; METABOLISM; PH; PROCEDURES; SPRAGUE DAWLEY RAT; TRANSPORT AT THE CELLULAR LEVEL;

ANIMALS; BIOLOGICAL TRANSPORT; BODY FLUIDS; DOSE-RESPONSE RELATIONSHIP, DRUG; HYDROGEN-ION CONCENTRATION; HYDROXYBUTYRATES; INJECTIONS, INTRAVENOUS; KIDNEY; LACTIC ACID; MALE; MEMBRANE TRANSPORT PROTEINS; RATS; RATS, SPRAGUE-DAWLEY; RENAL REABSORPTION;

EID: 84942503322     PISSN: 1567567X     EISSN: 15738744     Source Type: Journal    
DOI: 10.1007/s10928-015-9441-1     Document Type: Article

References (101)

1. Khurana I (2014) Excretory system. In: Textbook of human physiology for dental students, 2nd edn. Elsevier Health Sciences APAC, pp 280–281
2. Lote CJ (2000) Summary of the principal reabsorptive and secretory processes. In: Principles of renal physiology, 4th edn. Kluwer Academic Publishers, pp 161–162
3. Lash LH (2007) Principles and methods of renal toxicology. In: Hayes AW (ed) Principles and methods of toxicology, 5th edn. Taylor & Francis, London, pp 1513–1514
4. Kusuhara H, Sekine T, Anzai N, Endou H (2014) Drug transport in the kidney. In: Morris ME, Wang B (eds) You G. Drug transporters, Molecular characterization and role in drug disposition. Wiley, pp 303–316
5. Morrissey KM, Stocker SL, Wittwer MB, Xu L, Giacomini KM (2013) Renal transporters in drug development. Annu Rev Pharmacol Toxicol 53:503–529. doi:10.1146/annurev-pharmtox-011112-140317
6. Launay-Vacher V, Izzedine H, Karie S, Hulot JS, Baumelou A, Deray G (2006) Renal tubular drug transporters. Nephron Physiol 103(3):p97–p106. doi:10.1159/000092212
7. Morris ME, Hu K, Wang Q (2005) Renal clearance of gamma-hydroxybutyric acid in rats: increasing renal elimination as a detoxification strategy. J Pharmacol Exp Ther 313(3):1194–1202. doi:10.1124/jpet.105.083253
8. Iwanaga T, Kobayashi D, Hirayama M, Maeda T, Tamai I (2005) Involvement of uric acid transporter in increased renal clearance of the xanthine oxidase inhibitor oxypurinol induced by a uricosuric agent, benzbromarone. Drug Metab Dispos 33(12):1791–1795. doi:10.1124/dmd.105.006056
9. Shen H, Ocheltree SM, Hu Y, Keep RF, Smith DE (2007) Impact of genetic knockout of pept2 on cefadroxil pharmacokinetics, renal tubular reabsorption, and brain penetration in mice. Drug Metab Dispos 35(7):1209–1216. doi:10.1124/dmd.107.015263
10. Andersen ME, Clewell HJ 3rd, Tan YM, Butenhoff JL, Olsen GW (2006) Pharmacokinetic modeling of saturable, renal resorption of perfluoroalkylacids in monkeys–probing the determinants of long plasma half-lives. Toxicology 227(1–2):156–164. doi:10.1016/j.tox.2006.08.004
11. Chang SC, Noker PE, Gorman GS, Gibson SJ, Hart JA, Ehresman DJ, Butenhoff JL (2012) Comparative pharmacokinetics of perfluorooctanesulfonate (pfos) in rats, mice, and monkeys. Reprod Toxicol 33(4):428–440. doi:10.1016/j.reprotox.2011.07.002
12. Hendel J, Nyfors A (1984) Nonlinear renal elimination kinetics of methotrexate due to saturation of renal tubular reabsorption. Eur J Clin Pharmacol 26(1):121–124
13. Arvidsson A, Borga O, Alvan G (1979) Renal excretion of cephapirin and cephaloridine: evidence for saturable tubular reabsorption. Clin Pharmacol Ther 25(6):870–876
14. Fujino H, Saito T, Ogawa S, Kojima J (2005) Transporter-mediated influx and efflux mechanisms of pitavastatin, a new inhibitor of hmg-coa reductase. J Pharm Pharmacol 57(10):1305–1311. doi:10.1211/jpp.57.10.0009
15. Ho RH, Tirona RG, Leake BF, Glaeser H, Lee W, Lemke CJ, Wang Y, Kim RB (2006) Drug and bile acid transporters in rosuvastatin hepatic uptake: function, expression, and pharmacogenetics. Gastroenterology 130(6):1793–1806. doi:10.1053/j.gastro.2006.02.034
16. Su Y, Zhang X, Sinko PJ (2004) Human organic anion-transporting polypeptide oatp-a (slc21a3) acts in concert with p-glycoprotein and multidrug resistance protein 2 in the vectorial transport of saquinavir in hep g2 cells. Mol Pharm 1(1):49–56
17. Watanabe K, Jinriki T, Sato J (2004) Effects of progesterone and norethisterone on cephalexin uptake in the human intestinal cell line caco-2. Biol Pharm Bull 27(4):559–563
18. Li M, Anderson GD, Phillips BR, Kong W, Shen DD, Wang J (2006) Interactions of amoxicillin and cefaclor with human renal organic anion and peptide transporters. Drug Metab Dispos 34(4):547–555. doi:10.1124/dmd.105.006791
19. Wesson LG Jr (1954) A theoretical analysis of urea excretion by the mammalian kidney. Am J Physiol 179(2):364–371
20. Tucker GT (1981) Measurement of the renal clearance of drugs. Br J Clin Pharmacol 12(6):761–770
21. Hall S, Rowland M (1984) Relationship between renal clearance, protein binding and urine flow for digitoxin, a compound of low clearance in the isolated perfused rat kidney. J Pharmacol Exp Ther 228(1):174–179
22. Levy G (1980) Effect of plasma protein binding on renal clearance of drugs. J Pharm Sci 69(4):482–483
23. Sand TE, Jacobsen S (1981) Effect of urine ph and flow on renal clearance of methotrexate. Eur J Clin Pharmacol 19(6):453–456
24. Tang-Liu DD, Tozer TN, Riegelman S (1983) Dependence of renal clearance on urine flow: a mathematical model and its application. J Pharm Sci 72(2):154–158
25. Romano G, Favret G, Damato R, Bartoli E (1998) Proximal reabsorption with changing tubular fluid inflow in rat nephrons. Exp Physiol 83(1):35–48
26. Lang F (1987) Osmotic diuresis. Ren Physiol 10(3–4):160–173
27. Liu FY, Cogan MG (1984) Axial heterogeneity in the rat proximal convoluted tubule. I. Bicarbonate, chloride, and water transport. Am J Physiol 247(5 Pt 2):F816–F821
28. Liu FY, Cogan MG (1986) Axial heterogeneity of bicarbonate, chloride, and water transport in the rat proximal convoluted tubule. Effects of change in luminal flow rate and of alkalemia. J Clin Invest 78(6):1547–1557. doi:10.1172/JCI112747
29. Maddox DA, Gennari FJ (1987) The early proximal tubule: a high-capacity delivery-responsive reabsorptive site. Am J Physiol 252(4 Pt 2):F573–F584
30. Layton AT (2011) A mathematical model of the urine concentrating mechanism in the rat renal medulla. I. Formulation and base-case results. Am J Physiol Renal Physiol 300(2):F356–F371. doi:10.1152/ajprenal.00203.2010
31. Layton AT (2011) A mathematical model of the urine concentrating mechanism in the rat renal medulla. Ii. Functional implications of three-dimensional architecture. Am J Physiol Renal Physiol 300(2):F372–F384. doi:10.1152/ajprenal.00204.2010
32. Weinstein AM (2015) A mathematical model of the rat nephron: glucose transport. Am J Physiol Renal Physiol 308(10):F1098–F1118. doi:10.1152/ajprenal.00505.2014
33. Weinstein AM (2015) A mathematical model of rat proximal tubule and loop of henle. Am J Physiol Renal Physiol 308(10):F1076–F1097. doi:10.1152/ajprenal.00504.2014
34. Weinstein AM (2001) A mathematical model of rat cortical collecting duct: determinants of the transtubular potassium gradient. Am J Physiol Renal Physiol 280(6):F1072–F1092
35. Jusko WJ, Levy G (1970) Pharmacokinetic evidence for saturable renal tubular reabsorption of riboflavin. J Pharm Sci 59(6):765–772
36. Blanchard J, Tozer TN, Rowland M (1997) Pharmacokinetic perspectives on megadoses of ascorbic acid. Am J Clin Nutr 66(5):1165–1171
37. Yamaguchi K, Kato M, Suzuki M, Asanuma K, Aso Y, Ikeda S, Ishigai M (2011) Pharmacokinetic and pharmacodynamic modeling of the effect of an sodium-glucose cotransporter inhibitor, phlorizin, on renal glucose transport in rats. Drug Metab Dispos 39(10):1801–1807. doi:10.1124/dmd.111.040048
38. Lu Y, Griffen SC, Boulton DW, Leil TA (2014) Use of systems pharmacology modeling to elucidate the operating characteristics of sglt1 and sglt2 in renal glucose reabsorption in humans. Front Pharmacol 5:274. doi:10.3389/fphar.2014.00274
39. Demin O Jr, Yakovleva T, Kolobkov D, Demin O (2014) Analysis of the efficacy of sglt2 inhibitors using semi-mechanistic model. Front Pharmacol 5:218. doi:10.3389/fphar.2014.00218
40. Felmlee MA, Dave RA, Morris ME (2013) Mechanistic models describing active renal reabsorption and secretion: a simulation-based study. AAPS J 15(1):278–287. doi:10.1208/s12248-012-9437-3
41. Levy G (1965) Salicylurate formation demonstration of Michaelis-Menten kinetics in man. J Pharm Sci 54:496
42. Nelson E, Hanano M, Levy G (1966) Comparative pharmacokinetics of salicylate elimination in man and rats. J Pharmacol Exp Ther 153(1):159–166
43. Levy G, Weintraub L, Matsuzawa T, Oles SR (1966) Absorption, metabolism and excretion of salicylic phenolic glucuronide in rats. J Pharm Sci 55(11):1319–1320
44. Levy G, Tsuchiya T (1972) Salicylate accumulation kinetics in man. N Engl J Med 287(9):430–432. doi:10.1056/NEJM197208312870903
45. Levy G (1965) Effect of probenecid on blood levels and urinary recovery of ampicillin. Am J Med Sci 250:174–176
46. Levy G, Jusko WJ (1966) Apparent renal tubular secretion of riboflavin in man. J Pharm Sci 55(11):1322
47. Jusko WJ, Levy G (1967) Effect of probenecid on riboflavin absorption and excretion in man. J Pharm Sci 56(9):1145–1149
48. Jusko WJ, Levy G, Yaffe SJ, Gorodischer R (1970) Effect of probenecid on renal clearance of riboflavin in man. J Pharm Sci 59(4):473–477
49. Levy G, Koysooko R (1976) Renal clearance of theophylline in man. J Clin Pharmacol 16(7):329–332
50. Lowenthal DT, Oie S, Van Stone JC, Briggs WA, Levy G (1976) Pharmacokinetics of acetaminophen elimination by anephric patients. J Pharmacol Exp Ther 196(3):570–578
51. Lin JH, Levy G (1983) Renal clearance of inorganic sulfate in rats: effect of acetaminophen-induced depletion of endogenous sulfate. J Pharm Sci 72(3):213–217
52. Morris ME, Levy G (1984) Renal clearance and serum protein binding of acetaminophen and its major conjugates in humans. J Pharm Sci 73(8):1038–1041
53. Oie S, Levy G (1975) Relationship between renal function and elimination kinetics of pindolol in man. Eur J Clin Pharmacol 9(2–3):115–116
54. Morris ME, Levy G (1983) Serum concentration and renal excretion by normal adults of inorganic sulfate after acetaminophen, ascorbic acid, or sodium sulfate. Clin Pharmacol Ther 33(4):529–536
55. Galinsky RE, Slattery JT, Levy G (1979) Effect of sodium sulfate on acetaminophen elimination by rats. J Pharm Sci 68(6):803–805
56. Levy G, Calesnick B, Wase A (1964) Relationship between hg-203 excretion rate and diuretic response following hg-203 mercaptomerin sodium administration. J Nucl Med 5:302–303
57. Cummings AJ, Martin BK, Renton R (1966) The elimination of salicylic acid in man: serum concentrations and urinary excretion rates. Br J Pharmacol Chemother 26(2):461–467
58. Levy G (1980) Clinical pharmacokinetics of salicylates: a re-assessment. Br J Clin Pharmacol 10(Suppl 2):285S–290S
59. Oie S, Lowenthal DT, Briggs WA, Levy G (1975) Effect of hemodialysis on kinetics of acetaminophen elimination by anephric patients. Clin Pharmacol Ther 18(06):680–686
60. Levy G, Procknal J (1976) Letter: determination of salicylate and its metabolites in urine. Clin Chem 22(3):395
61. Levy G, Leonards JR (1971) Urine pH and salicylate therapy. JAMA 217(1):81
62. Levy G (1977) Pharmacokinetics in renal disease. Am J Med 62(4):461–465
63. Yacobi A, Levy G (1977) Intraindividual relationships between serum protein binding of drugs in normal human subjects, patients with impaired renal function, and rats. J Pharm Sci 66(9):1285–1288
64. Jusko WJ, Levy G (1967) Absorption, metabolism, and excretion of riboflavin-5’-phosphate in man. J Pharm Sci 56(1):58–62
65. Jusko WJ, Levy G (1969) Plasma protein binding of riboflavin and riboflavin-5’-phosphate in man. J Pharm Sci 58(1):58–62
66. Jusko WJ, Rennick BR, Levy G (1970) Renal exretion of riboflavin in the dog. Am J Physiol 218(4):1046–1053
67. Jusko WJ, Khanna N, Levy G, Stern L, Yaffe SJ (1970) Riboflavin absorption and excretion in the neonate. Pediatrics 45(6):945–949
68. Maitre M (1997) The gamma-hydroxybutyrate signalling system in brain: organization and functional implications. Prog Neurobiol 51(3):337–361
69. Mamelak M, Scharf MB, Woods M (1986) Treatment of narcolepsy with gamma-hydroxybutyrate. A review of clinical and sleep laboratory findings. Sleep 9(1 Pt 2):285–289
70. Gallimberti L, Spella MR, Soncini CA, Gessa GL (2000) Gamma-hydroxybutyric acid in the treatment of alcohol and heroin dependence. Alcohol 20(3):257–262
71. Wong CG, Gibson KM, Snead OC 3rd (2004) From the street to the brain: neurobiology of the recreational drug gamma-hydroxybutyric acid. Trends Pharmacol Sci 25(1):29–34
72. Schwartz RH, Milteer R, LeBeau MA (2000) Drug-facilitated sexual assault (‘date rape’). South Med J 93(6):558–561
73. Lettieri JT, Fung HL (1979) Dose-dependent pharmacokinetics and hypnotic effects of sodium gamma-hydroxybutyrate in the rat. J Pharmacol Exp Ther 208(1):7–11
74. Palatini P, Tedeschi L, Frison G, Padrini R, Zordan R, Orlando R, Gallimberti L, Gessa GL, Ferrara SD (1993) Dose-dependent absorption and elimination of gamma-hydroxybutyric acid in healthy volunteers. Eur J Clin Pharmacol 45(4):353–356
75. Scharf MB, Lai AA, Branigan B, Stover R, Berkowitz DB (1998) Pharmacokinetics of gammahydroxybutyrate (ghb) in narcoleptic patients. Sleep 21(5):507–514
76. Arena C, Fung HL (1980) Absorption of sodium gamma-hydroxybutyrate and its prodrug gamma-butyrolactone: relationship between in vitro transport and in vivo absorption. J Pharm Sci 69(3):356–358
77. Sporer KA, Chin RL, Dyer JE, Lamb R (2003) Gamma-hydroxybutyrate serum levels and clinical syndrome after severe overdose. Ann Emerg Med 42(1):3–8. doi:10.1067/mem.2003.253
78. Cui D, Morris ME (2009) The drug of abuse gamma-hydroxybutyrate is a substrate for sodium-coupled monocarboxylate transporter (smct) 1 (slc5a8): characterization of smct-mediated uptake and inhibition. Drug Metab Dispos 37(7):1404–1410. doi:10.1124/dmd.109.027169
79. Wang Q, Lu Y, Morris ME (2007) Monocarboxylate transporter (mct) mediates the transport of gamma-hydroxybutyrate in human kidney hk-2 cells. Pharm Res 24(6):1067–1078. doi:10.1007/s11095-006-9228-6
80. Wang Q, Wang X, Morris ME (2008) Effects of l-lactate and d-mannitol on gamma-hydroxybutyrate toxicokinetics and toxicodynamics in rats. Drug Metab Dispos 36(11):2244–2251. doi:10.1124/dmd.108.022996
81. Morse BL, Vijay N, Morris ME (2014) Mechanistic modeling of monocarboxylate transporter-mediated toxicokinetic/toxicodynamic interactions between gamma-hydroxybutyrate and l-lactate. AAPS J 16(4):756–770. doi:10.1208/s12248-014-9593-8
82. Vijay N, Morse BL, Morris ME (2015) A novel monocarboxylate transporter inhibitor as a potential treatment strategy for gamma-hydroxybutyric acid overdose. Pharm Res 32(6):1894–1906. doi:10.1007/s11095-014-1583-0
83. Morse BL, Morris ME (2013) Effects of monocarboxylate transporter inhibition on the oral toxicokinetics/toxicodynamics of gamma-hydroxybutyrate and gamma-butyrolactone. J Pharmacol Exp Ther 345(1):102–110. doi:10.1124/jpet.112.202796
84. Morris ME, Morse BL, Baciewicz GJ, Tessena MM, Acquisto NM, Hutchinson DJ, Dicenzo R (2011) Monocarboxylate transporter inhibition with osmotic diuresis increases gamma-hydroxybutyrate renal elimination in humans: a proof-of-concept study. J Clin Toxicol 1(2):1000105. doi:10.4172/2161-0495.1000105
85. Felmlee MA, Wang Q, Cui D, Roiko SA, Morris ME (2010) Mechanistic toxicokinetic model for gamma-hydroxybutyric acid: inhibition of active renal reabsorption as a potential therapeutic strategy. AAPS J 12(3):407–416. doi:10.1208/s12248-010-9197-x
86. Wang Q, Darling IM, Morris ME (2006) Transport of gamma-hydroxybutyrate in rat kidney membrane vesicles: role of monocarboxylate transporters. J Pharmacol Exp Ther 318(2):751–761. doi:10.1124/jpet.106.105965
87. Yanase H, Takebe K, Nio-Kobayashi J, Takahashi-Iwanaga H, Iwanaga T (2008) Cellular expression of a sodium-dependent monocarboxylate transporter (slc5a8) and the mct family in the mouse kidney. Histochem Cell Biol 130(5):957–966. doi:10.1007/s00418-008-0490-z
88. Woodhall PB, Tisher CC (1973) Response of the distal tubule and cortical collecting duct to vasopressin in the rat. J Clin Invest 52(12):3095–3108. doi:10.1172/JCI107509
89. Morse BL, Felmlee MA, Morris ME (2012) Gamma-hydroxybutyrate blood/plasma partitioning: effect of physiologic ph on transport by monocarboxylate transporters. Drug Metab Dispos 40(1):64–69. doi:10.1124/dmd.111.041285
90. D’Argenio DZ, Schumitzky A, Wang X (2009) Adapt 5 user’s guide: pharmacokinetic/pharmacodynamic systems analysis software, 4th edn. Biomedical Simulations Resource, Los Angeles, CA
91. Lyon RC, Johnston SM, Panopoulos A, Alzeer S, McGarvie G, Ellis EM (2009) Enzymes involved in the metabolism of gamma-hydroxybutyrate in sh-sy5y cells: identification of an iron-dependent alcohol dehydrogenase adhfe1. Chem Biol Interact 178(1–3):283–287. doi:10.1016/j.cbi.2008.10.025
92. Edlund GL, Halestrap AP (1988) The kinetics of transport of lactate and pyruvate into rat hepatocytes. Evidence for the presence of a specific carrier similar to that in erythrocytes. Biochem J 249(1):117–126
93. Ganapathy V, Thangaraju M, Gopal E, Martin PM, Itagaki S, Miyauchi S, Prasad PD (2008) Sodium-coupled monocarboxylate transporters in normal tissues and in cancer. AAPS J 10(1):193–199. doi:10.1208/s12248-008-9022-y
94. Wang Q, Morris ME (2007) The role of monocarboxylate transporter 2 and 4 in the transport of gamma-hydroxybutyric acid in mammalian cells. Drug Metab Dispos 35(8):1393–1399. doi:10.1124/dmd.107.014852
95. Felmlee MA, Krzyzanski W, Morse BL, Morris ME (2011) Use of a local sensitivity analysis to inform study design based on a mechanistic toxicokinetic model for gamma-hydroxybutyric acid. AAPS J 13(2):240–254. doi:10.1208/s12248-011-9264-y
96. Halestrap AP (2012) The monocarboxylate transporter family–structure and functional characterization. IUBMB Life 64(1):1–9. doi:10.1002/iub.573
97. Meno-Tetang GM, Li H, Mis S, Pyszczynski N, Heining P, Lowe P, Jusko WJ (2006) Physiologically based pharmacokinetic modeling of fty720 (2-amino-2[2-(-4-octylphenyl)ethyl]propane-1,3-diol hydrochloride) in rats after oral and intravenous doses. Drug Metab Dispos 34(9):1480–1487. doi:10.1124/dmd.105.009001
98. Peters SA (2012) Appendices. In: Physiologically-based pharmacokinetic (pbpk) modeling and simulations: principles, methods, and applications in the pharmaceutical industry. Wiley, p 407
99. Niederalt C, Wendl T, Kuepfer L, Claassen K, Loosen R, Willmann S, Lippert J, Schultze-Mosgau M, Winkler J, Burghaus R, Brautigam M, Pietsch H, Lengsfeld P (2012) Development of a physiologically based computational kidney model to describe the renal excretion of hydrophilic agents in rats. Front Physiol 3:494. doi:10.3389/fphys.2012.00494
100. Jobin J, Bonjour JP (1985) Measurement of glomerular filtration rate in conscious unrestrained rats with inulin infused by implanted osmotic pumps. Am J Physiol 248(5 Pt 2):F734–F738
101. Wang X, Wang Q, Morris ME (2008) Pharmacokinetic interaction between the flavonoid luteolin and gamma-hydroxybutyrate in rats: potential involvement of monocarboxylate transporters. AAPS J 10(1):47–55. doi:10.1208/s12248-007-9001-8