The population pharmacokinetics of D-β-hydroxybutyrate following administration of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate

AAPS Journal

Volumn 18, Issue 3, 2016, Pages 678-688

  Shivva, Vittal ^a   Cox, Pete J ^b   Clarke, Kieran ^b   Veech, Richard L ^c   Tucker, Ian G ^a   Duffull, Stephen B ^a  

^a UNIVERSITY OF OTAGO   (New Zealand)

^b UNIVERSITY OF OXFORD   (United Kingdom)

^c NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM   (United States)

Author keywords

D hydroxybutyrate; Exogenous ketosis; Ketone monoester; Pharmacokinetics; Population models

Indexed keywords

3 HYDROXYBUTYL 3 HYDROXYBUTYRIC ACID; DEXTRO BETA HYDROXYBUTYRIC ACID; HYDROXYBUTYRIC ACID; KETONE; KETONE MONOESTER; UNCLASSIFIED DRUG;

ADULT; ARTICLE; BLOOD SAMPLING; BODY HEIGHT; CONTROLLED STUDY; DRUG ABSORPTION; DRUG BIOAVAILABILITY; DRUG CLEARANCE; DRUG ELIMINATION; DRUG FORMULATION; DRUG HYDROLYSIS; FEMALE; HUMAN; HUMAN EXPERIMENT; LEAN BODY WEIGHT; LIMIT OF DETECTION; LIMIT OF QUANTITATION; MALE; NORMAL HUMAN; VOLUME OF DISTRIBUTION; THEORETICAL MODEL;

FEMALE; HUMANS; HYDROXYBUTYRATES; MALE; MODELS, THEORETICAL;

EID: 85007478605     PISSN: None     EISSN: 15507416     Source Type: Journal    
DOI: 10.1208/s12248-016-9879-0     Document Type: Article

References (42)

1. Veech RL, Chance B, Kashiwaya Y, Lardy HA, Cahill JGF. Ketone bodies, potential therapeutic uses. IUBMB life. 2001;51(4):241-7.
2. Harvey RAPD, Ferrier DR, Champe PC. Biochemistry. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins; 2011.
3. Cahill JGF, Veech RL. Ketoacids? Good medicine? Trans Am Clin Climatol Assoc. 2003;114:149-63.
4. Cahill Jr GF. Starvation in man. N Engl J Med. 1970;282(12):668-75.
5. Mitchell GA, Kassovska-Bratinova S, Boukaftane Y, Robert MF, Wang SP, Ashmarina L, et al. Medical aspects of ketone body metabolism. Clin Invest Med. 1995;18(3):193-216.
6. Laffel L. Ketone bodies: a review of physiology, pathophysiology and application of monitoring to diabetes. Diabetes Metab Res Rev. 1999;15(6):412-26.
7. Freeman JM, Kossoff EH, Hartman AL. The ketogenic diet: one decade later. Pediatrics. 2007;119(3):535-43.
8. Henderson ST. Ketone bodies as a therapeutic for Alzheimer’s disease. Neurotherapeutics. 2008;5(3):470-80.
9. Kashiwaya Y, Takeshima T, Mori N, Nakashima K, Clarke K, Veech RL. D-beta-hydroxybutyrate protects neurons in models of Alzheimer’s and Parkinson’s disease. Proc Natl Acad Sci USA. 2000;97(10):5440-4.
10. Kashiwaya Y, Bergman C, Lee JH, Wan R, King MT, Mughal MR, et al. A ketone ester diet exhibits anxiolytic and cognition-sparing properties, and lessens amyloid and tau pathologies in a mouse model of Alzheimer’s disease. Neurobiol Aging. 2013;34(6):1530-9.
11. Cox PJ, Clarke K. Acute nutritional ketosis: implications for exercise performance and metabolism. Extrem Physiol Med. 2014;3:17-7.
12. Lee CY. The effect of high-fat diet-induced pathophysiological changes in the gut on obesity: what should be the ideal treatment? Clin Transl Gastroenterol. 2013;4(7):e39.
13. Clarke K, Tchabanenko K, Pawlosky R, Carter E, Todd King M, Musa-Veloso K, et al. Kinetics, safety and tolerability of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate in healthy adult subjects. Regul Toxicol Pharmacol. 2012;63(3):401-8.
14. Liederer BM, Borchardt RT. Enzymes involved in the bioconversion of ester-based prodrugs. J Pharm Sci. 2006;95(6):1177-95.
15. Satoh T, Hosokawa M. Structure, function and regulation of carboxylesterases. Chem Biol Interact. 2006;162(3):195-211.
16. Garber AJ, Menzel PH, Boden G, Owen OE. Hepatic ketogenesis and gluconeogenesis in humans. J Clin Invest. 1974;54(4):981-9.
17. Owen OE. Ketone bodies as a fuel for the brain during starvation. Biochem Mol Biol Educ. 2005;33(4):246-51.
18. Balasse EO. Kinetics of ketone body metabolism in fasting humans. Metabolism. 1979;28(1):41-50.
19. Cobelli C, Nosadini R, Toffolo G, McCulloch A, Avogaro A, Tiengo A, et al. Model of the kinetics of ketone bodies in humans. Am J Physiol. 1982;243(1):7-17.
20. Wastney ME, Hall SE, Berman M. Ketone body kinetics in humans: a mathematical model. J Lipid Res. 1984;25(2):160-74.
21. Hall SE, Wastney ME, Bolton TM, Braaten JT, Berman M. Ketone body kinetics in humans: the effects of insulin-dependent diabetes, obesity, and starvation. J Lipid Res. 1984;25(11):1184-94.
22. Balasse EO, Fery F. Ketone body production and disposal: effects of fasting, diabetes, and exercise. Diabetes Metab Rev. 1989;5(3):247-70.
23. Janmahasatian S, Duffull SB, Ash S, Ward LC, Byrne NM, Green B. Quantification of lean bodyweight. Clin Pharmacokinet. 2005;44(10):1051-65.
24. Abbott. Clinical Evaluation of a Faster, Smaller Sample Volume Blood ß-Ketone Test Strip Abbott Diabetes Care Inc. 2006. Available from: https://abbottdiabetescare.co.uk/images/uploads/documents/08_KII_white__paper.pdf Accessed 2 September 2013.
25. Guerci B, Benichou M, Floriot M, Bohme P, Fougnot S, Franck P, et al. Accuracy of an electrochemical sensor for measuring capillary blood ketones by fingerstick samples during metabolic deterioration after continuous subcutaneous insulin infusion interruption in type 1 diabetic patients. Diabetes Care. 2003;26(4):1137-41.
26. Forrow NJ, Sanghera GS, Walters SJ, Watkin JL. Development of a commercial amperometric biosensor electrode for the ketone D-3-hydroxybutyrate. Biosens Bioelectron. 2005;20(8):1617-25.
27. Bauer RJ. NONMEM users guide introduction to NONMEM 7.2.0. Ellicott City: ICON Development Solutions; 2011.
28. Beal S. Ways to fit a PK model with some data below the quantification limit. J Pharmacokinet Pharmacodyn. 2001;28(5):481-504.
29. Dansirikul C, Silber HE, Karlsson MO. Approaches to handling pharmacodynamic baseline responses. J Pharmacokinet Pharmacodyn. 2008;35(3):269-83.
30. Kumar VVP, Oscarsson S, Friberg LE, Isbister GK, Hackett LP, Duffull SB. The effect of decontamination procedures on the pharmacokinetics of venlafaxine in overdose. Clin Pharmacol Ther. 2009;86(4):403-10.
31. Karlsson MO, Holford N. A tutorial on visual predictive checks. Marseille: Population Approach Group Europe PAGE; 2008.
32. Bergstrand M, Hooker AC, Wallin JE, Karlsson MO. Prediction-corrected visual predictive checks for diagnosing nonlinear mixed-effects models. AAPS J. 2011;13(2):143-51.
33. Savic RM, Karlsson MO. Importance of shrinkage in empirical bayes estimates for diagnostics: problems and solutions. AAPS J. 2009;11(3):558-69.
34. Desrochers S, Dubreuil P, Brunet J, Jette M, David F, Landau BR, et al. Metabolism of (R, S)-1,3-butanediol acetoacetate esters, potential parenteral and enteral nutrients in conscious pigs. Am J Physiol. 1995;268(4 Pt 1):E660-7.
35. Jones AW, Eklund A, Kronstrand R. Concentration-time profiles of gamma-hydroxybutyrate in blood after recreational doses are best described by zero-order rather than first-order kinetics. J Anal Toxicol. 2009;33(6):332-5.
36. Halestrap AP, Price NT. The proton-linked monocarboxylate transporter (MCT) family: structure, function and regulation. Biochem J. 1999;343(Pt 2):281-99.
37. Gill RK, Saksena S, Alrefai WA, Sarwar Z, Goldstein JL, Carroll RE, et al. Expression and membrane localization of MCT isoforms along the length of the human intestine. Am J Physiol Cell Physiol. 2005;289(4):C846-52.
38. Broer S, Schneider HP, Broer A, Rahman B, Hamprecht B, Deitmer JW. Characterization of the monocarboxylate transporter 1 expressed in Xenopus laevis oocytes by changes in cytosolic pH. Biochem J. 1998;333(Pt 1):167-74.
39. Broer S, Broer A, Schneider HP, Stegen C, Halestrap AP, Deitmer JW. Characterization of the high-affinity monocarboxylate transporter MCT2 in Xenopus laevis oocytes. Biochem J. 1999;341(Pt 3):529-35.
40. Nosadini R, Avogaro A, Doria A, Fioretto P, Trevisan R, Morocutti A. Ketone body metabolism: a physiological and clinical overview. Diabetes Metab Rev. 1989;5(3):299-319.
41. Poole RC, Halestrap AP. Transport of lactate and other monocarboxylates across mammalian plasma membranes. Am J Physiol. 1993;264(4 Pt 1):C761-82.
42. Balasse EO, Neef MA. Inhibition of ketogenesis by ketone bodies in fasting humans. Metabolism. 1975;24(9):999-1007.