Development of multi-route physiologically-based pharmacokinetic models for ethanol in the adult, pregnant, and neonatal rat

Inhalation Toxicology

Volumn 24, Issue 11, 2012, Pages 698-722

  Martin, Sheppard A ^a,e   McLanahan, Eva D ^b,e   El Masri, Hisham ^c,e   Lefew, William R ^c,e   Bushnell, Philip J ^a,e   Boyes, William K ^a,e   Choi, Kyoungju ^d   Clewell III, Harvey J ^d   Campbell, Jerry L ^d  

^a NB TAD NHEERL ORD   (United States)

^b NCEA ORD   (United States)

^c SBB ISTD ORD   (United States)

^d HAMNER INSTITUTES FOR HEALTH SCIENCES   (United States)

^e U S ENVIRONMENTAL PROTECTION AGENCY   (United States)

Author keywords

Ethanol; Life stage; Multi route; PBPK model; Pharmacokinetics

Indexed keywords

ALCOHOL; BIOFUEL;

ABSORPTION; ARTICLE; CLEARANCE; CONCENTRATION (PARAMETERS); CONTROLLED STUDY; FEEDING; PRIORITY JOURNAL; SIMULATION;

ANIMALIA; RATTUS;

EID: 84866101195     PISSN: 08958378     EISSN: 10917691     Source Type: Journal    
DOI: 10.3109/08958378.2012.712165     Document Type: Article

References (113)

1. Abel EL. 2006. Fetal alcohol syndrome: A cautionary note. Curr Pharm Des 12:1521-1529.
2. Aragon CM, Rogan F, Amit Z. 1992. Ethanol metabolism in rat brain homogenates by a catalase-H2O2 system. Biochem harmacol 44:93-98.
3. Badger TM, Hidestrand M, Shankar K, McGuinn WD, Ronis MJ. The effects of pregnancy on ethanol clearance. Life Sci 77:2111-2126.
4. Bandla HPR, Simakajornboon N, Graff GR, Gozal D. 1999. Protein kinase C modulates ventilatory patterning in the developing rat. Am J Respir Crit Care Med 159:968-973.
5. Bani D, Baccari MC, Quattrone S, Nistri S, Calamai F, Bigazzi M, Bani Sacchi T. 2002. Relaxin depresses small bowel motility through a nitric oxide-mediated mechanism. Studies in mice. Biol Reprod 66:778-784.
6. Baraona E, Abittan CS, Dohmen K, Moretti M, Pozzato G, Chayes ZW, Schaefer C, Lieber CS. 2001. Gender differences in pharmacokinetics of alcohol. Alcohol Clin Exp Res 25:502-507.
7. Baraona E, Shoichet L, Navder K, Lieber CS. 2002. Mediation by nitric oxide of the stimulatory effects of ethanol on blood flow. Life Sci 70:2987-2995.
8. Barnhill MT Jr, Herbert D, Wells DJ Jr. 2007. Comparison of hospital laboratory serum alcohol levels obtained by an enzymatic method with whole blood levels forensically determined by gas chromatography. J Anal Toxicol 31:23-30.
9. Baron TH, Ramirez B, Richter JE. 1993. Gastrointestinal motility disorders during pregnancy. Ann Intern Med 118:366-375.
10. Berman RF, Hannigan JH. 2000. Effects of prenatal alcohol exposure on the hippocampus: Spatial behavior, electrophysiology, and neuroanatomy. Hippocampus 10:94-110.
11. Bonthius DJ, Goodlett CR, West Jr. 1988. Blood alcohol concentration and severity of microencephaly in neonatal rats depend on the pattern of alcohol administration. Alcohol 5:209-214.
12. Braggins TJ, Crow KE. 1981. The effects of high ethanol doses on rates of ethanol oxidation in rats. A reassessment of factors controlling rates of ethanol oxidation in vivo. Eur J Biochem 119:633-640.
13. Burden MJ, Jacobson SW, Jacobson JL. 2005. Relation of prenatal alcohol exposure to cognitive processing speed and efficiency in childhood. Alcohol Clin Exp Res 29:1473-1483.
14. Bushnell P, Beasley T, Boyes W, El-Masri H, Evansky P, Ford J, Gilbert M, Herr D, LeFew W, Martin S, McDaniel K, McLanahan E, Moser V, Oshiro W. 2011. Biofuels Health Research at the EPA: Initial Studies with Inhaled Ethanol in Rats, 2610. The Toxicologist CD - An official Journal of the Society of Toxicology 125.
15. Caballeria J, Baraona E, Rodamilans M, Lieber CS. 1989. Effects of cimetidine on gastric alcohol dehydrogenase activity and blood ethanol levels. Gastroenterology 96:388-392.
16. Carmichael FJ, Saldivia V, Israel Y, McKaigney JP, Orrego H. 1987. Ethanol-induced increase in portal hepatic blood flow: Interference by anesthetic agents. Hepatology 7:89-94.
17. Carneiro LM, Diógenes JP, Vasconcelos SM, Aragão GF, Noronha EC, Gomes PB, Viana GS. 2005. Behavioral and neurochemical effects on rat offspring after prenatal exposure to ethanol. Neurotoxicol Teratol 27:585-592.
18. Centers for Disease Control and Prevention. 2010. Alcohol and Public Health: Frequently Asked Questions. http://www.cdc.gov/
19. alcohol/faqs.htm#top. Chan DQ. 1999. Fetal alcohol syndrome. Optom Vis Sci 76:678-685.
20. Charlebois RC, Corbett MR, Wigmore JG. 1996. Comparison of ethanol concentrations in blood, serum, and blood cells for forensic application. J Anal Toxicol 20:171-178.
21. Chen TS, Doong ML, Chang FY, Lee SD, Wang PS. 1995. Effects of sex steroid hormones on gastric emptying and gastrointestinal transit in rats. Am J Physiol 268:G171-G176.
22. Chen WJ, Maier SE, Parnell SE, West Jr. 2003. Alcohol and the developing brain: Neuroanatomical studies. Alcohol Res Health 27:174-180.
23. Chiloiro M, Darconza G, Piccioli E, De Carne M, Clemente C, Riezzo G. 2001. Gastric emptying and orocecal transit time in pregnancy. J Gastroenterol 36:538-543.
24. Clewell HJ 3rd, Gentry PR, Gearhart JM, Covington TR, Banton MI, Andersen ME. 2001. Development of a physiologically based pharmacokinetic model of isopropanol and its metabolite acetone. Toxicol Sci 63:160-172.
25. Coskun T, Sevinç A, Tevetoglu I, Alican I, Kurtel H, Yegen BC. 1995. Delayed gastric emptying in conscious male rats following chronic estrogen and progesterone treatment. Res Exp Med (Berl 49-54.
26. Cragg B, Phillips S. 1985. Natural loss of Purkinje cells during development and increased loss with alcohol. Brain Res 325:151-160.
27. Datz FL, Christian PE, Moore J. 1987. Gender-related differences in gastric emptying. J Nucl Med 28:1204-1207.
28. Davies M. 2003. The role of GABAA receptors in mediating the effects of alcohol in the central nervous system. J Psychiatry Neurosci 28:263-274.
29. Eriksson CJ, Sippel HW. 1977. The distribution and metabolism of acetaldehyde in rats during ethanol oxidation-I. The distribution of acetaldehyde in liver, brain, blood and breath. Biochem Pharmacol 26:241-247.
30. Gentry PR, Covington TR, Andersen ME, Clewell HJ 3rd. 2002. Application of a physiologically based pharmacokinetic model for isopropanol in the derivation of a reference dose and reference concentration. Regul Toxicol Pharmacol 36:51-68.
31. Gentry RT. 2000. Effect of food on the pharmacokinetics of alcohol absorption. Alcohol Clin Exp Res 24:403-404.
32. Gómez RA, Fulginiti S, Ramírez OA. 1992. Effect of acute ethanol exposure during pregnancy on dentate gyrus synaptic plasticity in 45-day-old rats. Pharmacol Biochem Behav 42:85-89.
33. Goodlett CR, Eilers AT. 1997. Alcohol-induced Purkinje cell loss with a single binge exposure in neonatal rats: A stereological study of temporal windows of vulnerability. Alcohol Clin Exp Res 21:738-744.
34. Gupta T, Chen L, Groszmann R. 1997. Bailliere's clinical gastroenterology.
35. Hamby-Mason R, Chen JJ, Schenker S, Perez A, Henderson GI. 1997.Catalase mediates acetaldehyde formation from ethanol in fetal and neonatal rat brain. Alcohol Clin Exp Res 21:1063-1072.
36. Haseba T, Kameyama K, Mashimo K, Ohno Y. 2012. Dose-Dependent Change in Elimination Kinetics of Ethanol due to Shift of Dominant Metabolizing Enzyme from ADH 1 (Class I) to ADH 3 (Class III) in Mouse. Int J Hepatol 2012:408190.
37. Hayashi M, Shimazaki Y, Kamata S, Kakiichi N, Ikeda M. 1991. Disposition of ethanol and acetaldehyde in maternal blood, fetal blood, and amniotic fluid of near-term pregnant rats. Bull Environ Contam Toxicol 47:184-189.
38. He J, de la Monte S, Wands Jr. 2007. Acute ethanol exposure inhibits insulin signaling in the liver. Hepatology 46:1791-1800.
39. He L, Ronis MJ, Badger TM. 2002. Ethanol induction of class I alcohol dehydrogenase expression in the rat occurs through alterations in CCAAT/enhancer binding proteins beta and gamma. J Biol Chem 277:43572-43577.
40. Heimann G. 1980. Enteral absorption and bioavailability in children in relation to age. Eur J Clin Pharmacol 18:43-50.
41. Hindmarch I, Kerr JS, Sherwood N. 1991. The effects of alcohol and other drugs on psychomotor performance and cognitive function. Alcohol Alcohol 26:71-79.
42. Holt S. 1981. Observations on the relation between alcohol absorption and the rate of gastric emptying. Can Med Assoc J 124:267-77, 297.
43. Hutson WR, Roehrkasse RL, Wald A. 1989. Influence of gender and menopause on gastric emptying and motility. Gastroenterology 96:11-17.
44. Ikonomidou C, Bosch F, Miksa M, Bittigau P, Vöckler J, Dikranian K, Tenkova TI, Stefovska V, Turski L, Olney JW. 1999. Blockade of NMDA receptors and apoptotic neurodegeneration in the developing brain. Science 283:70-74.
45. Ikonomidou C, Bittigau P, Ishimaru MJ, Wozniak DF, Koch C, Genz K, Price MT, Stefovska V, Hörster F, Tenkova T, Dikranian K, Olney JW. 2000. Ethanol-induced apoptotic neurodegeneration and fetal alcohol syndrome. Science 287:1056-1060.
46. ILSI. 1994. Physiological Parameter Values for PBPK Models.
47. Washington, D.C: International Life Sciences Institute (ILSI) Risk Science Institute (RSI), 1-142.
48. Kaminen-Ahola N, Ahola A, Maga M, Mallitt KA, Fahey P, Cox TC, Whitelaw E, Chong S. 2010. Maternal ethanol consumption alters the epigenotype and the phenotype of offspring in a mouse model. PLoS Genet 6:e1000811.
49. Kaneko T, Wang PY, Sato A. 1994. Partition coefficients of some acetate esters and alcohols in water, blood, olive oil, and rat tissues. Occup Environ Med 51:68-72.
50. Kelly SJ, Bonthius DJ, West Jr. 1987. Developmental changes in alcohol pharmacokinetics in rats. Alcohol Clin Exp Res 11:281-286.
51. Kozawa S, Yukawa N, Liu J, Shimamoto A, Kakizaki E, Fujimiya T. 2007. Effect of chronic ethanol administration on disposition of ethanol and its metabolites in rat. Alcohol 41:87-93.
52. Lancaster FE, Phillips SM, Patsalos PN, Wiggins RC. 1984. Brain myelination in the offspring of ethanol-treated rats: In utero versus lactational exposure by crossfostering offspring of control, pairfed and ethanol treated dams. Brain Res 309:209-216.
53. Lawson M, Kern F Jr, Everson GT. 1985. Gastrointestinal transit time in human pregnancy: Prolongation in the second and third trimesters followed by postpartum normalization. Gastroenterology 89:996-999.
54. Levitt MD, Levitt DG. 1994. The critical role of the rate of ethanol absorption in the interpretation of studies purporting to demonstrate gastric metabolism of ethanol. J Pharmacol Exp Ther 269:297-304.
55. Levitt MD, Li R, DeMaster EG, Elson M, Furne J, Levitt DG. 1997. Use of measurements of ethanol absorption from stomach and intestine to assess human ethanol metabolism. Am J Physiol 273:G951-G957.
56. Lieber CS, DeCarli LM. 1970. Hepatic microsomal ethanol-oxidizing system. In vitro characteristics and adaptive properties in vivo. J Biol Chem 245:2505-2512.
57. Lieber CS. 1999. Microsomal ethanol-oxidizing system (MEOS): The first 30 years (1968-1998)-a review. Alcohol Clin Exp Res 23:991-1007.
58. Lim RT Jr, Gentry RT, Ito D, Yokoyama H, Baraona E, Lieber CS. 1993. First-pass metabolism of ethanol is predominantly gastric. Alcohol Clin Exp Res 17:1337-1344.
59. Liu CY, Chen LB, Liu PY, Xie DP, Wang PS. 2002. Effects of progesterone on gastric emptying and intestinal transit in male rats. World J Gastroenterol 8:338-341.
60. Loizou GD, Spendiff M. 2004. A human PBPK model for ethanol describing inhibition of gastric motility. J Mol Histol 35:687-696.
61. Lolli G, Rubin M. 1943a. The effect of concentration of alcohol on the rate of absorption and the shape of the blood alcohol curve. Quart J Stud Alcohol 4:57-63.
62. Lolli G, Rubin M. 1943b. Alcohol and the emptying time of the stomach. Quart J Stud Alcohol 4:64-67.
63. MacGregor RR. 1986. Alcohol and immune defense. JAMA 256: 1474-1479.
64. Majchrowicz E. 1975. Induction of physical dependence upon ethanol and the associated behavioral changes in rats. Psychopharmacologia 43:245-254.
65. Marietta CA, Jerrells TR, Meagher RC, Karanian JW, Weight FF, Eckardt MJ. 1988. Effects of long-term ethanol inhalation on the immune and hematopoietic systems of the rat. Alcohol Clin Exp Res 12:211-214.
66. Martin S, Campbell J, Choi K, Clewell H, El-Masri H, LeFew W, Beasley T, Oshiro W, Degn L, Evansky P, Ledbetter A, Ford J, Herr D, Boyes W, Bushnell P, McLanahan E. 2011. Life-stage PBPK models for multiple routes of ethanol exposure in the rat, 707. The Toxicologist CD - An official Journal of the Society of Toxicology 125.
67. Martin S, Oshiro W, Evansky P, Ledbetter A, Ford J, Krantz Q, Degn L, LeFew W, Beasley T, Campbell J, Choi K, Clewell III H, El-Masri H, Boyes W, Bushnell P, McLanahan E. 2012. Application of life-stage PBPK models for ethanol exposure in the rat. Manuscript in preparation. McKillop IH, Schrum LW. 2005. Alcohol and liver cancer. Alcohol 35:195-203.
68. Milsap RL, Jusko WJ. 1994. Pharmacokinetics in the infant. Environ Health Perspect 102 Suppl 11:107-110.
69. Mirfazaelian A, Kim KB, Lee S, Kim HJ, Bruckner JV, Fisher JW. 2007. Organ growth functions in maturing male Sprague-Dawley rats. J Toxicol Environ Health Part A 70:429-438.
70. Montpied P, Morrow AL, Karanian JW, Ginns EI, Martin BM, Paul SM. 1991. Prolonged ethanol inhalation decreases gammaaminobutyric acidA receptor alpha subunit mRNAs in the rat cerebral cortex. Mol Pharmacol 39:157-163.
71. Morzorati SL, Ramchandani VA, Li TK, O'Connor S. 2002. Maintaining steady state arterial alcohol levels in rats by using a physiologically based pharmacokinetic model. Alcohol 28:189-195.
72. Nelson BK, Brightwell WS, MacKenzie DR, Khan A, Burg JR, Weigel WW, Goad PT. 1985. Teratological assessment of methanol and ethanol at high inhalation levels in rats. Fundam Appl Toxicol 5:727-736.
73. Nixon K, Crews FT. 2002. Binge ethanol exposure decreases neurogenesis in adult rat hippocampus. J Neurochem 83:1087-1093.
74. Nixon K. 2006. Alcohol and adult neurogenesis: Roles in neurodegeneration and recovery in chronic alcoholism. Hippocampus 16:287-295.
75. Norman NA, Bruce NW. 1979. Fetal and placental weight relationships in the rat at days 13 and 17 of gestation. J Reprod Fertil 57:345-348.
76. O'Flaherty EJ, Scott W, Schreiner C, Beliles RP. 1992. A physiologically based kinetic model of rat and mouse gestation: disposition of a weak acid. Toxicol Appl Pharmacol 112:245-256.
77. Obernier JA, White AM, Swartzwelder HS, Crews FT. 2002. Cognitive deficits and CNS damage after a 4-day binge ethanol exposure in rats. Pharmacol Biochem Behav 72:521-532.
78. Pastino GM, Sultatos LG, Flynn EJ. 1996. Development and application of a physiologically based pharmacokinetic model for ethanol in the mouse. Alcohol Alcohol 31:365-374.
79. Pastino GM, Asgharian B, Roberts K, Medinsky MA, Bond JA. 1997. A comparison of physiologically based pharmacokinetic model predictions and experimental data for inhaled ethanol in male and female B6C3F1 mice, F344 rats, and humans. Toxicol Appl Pharmacol 145:147-157.
80. Pastino GM, Conolly RB. 2000. Application of a physiologically based pharmacokinetic model to estimate the bioavailability of ethanol in male rats: distinction between gastric and hepatic pathways of metabolic clearance. Toxicol Sci 55:256-265.
81. Penetar DM, McNeil JF, Ryan ET, Lukas SE. 2008. Comparison among plasma, serum, and whole blood ethanol concentrations: Impact of storage conditions and collection tubes. J Anal Toxicol 32: 505-510.
82. Phillips SC, Cragg BG. 1982. A change in susceptibility of rat cerebellar Purkinje cells to damage by alcohol during fetal, neonatal and adult life. Neuropathol Appl Neurobiol 8:441-454.
83. Phillips SC. 1985. Age-dependent susceptibility of rat cerebellar Purkinje cells to ethanol exposure. Drug Alcohol Depend 16:273-277.
84. Pierce DR, West Jr. 1986. Alcohol-induced microencephaly during the third trimester equivalent: Relationship to dose and blood alcohol concentration. Alcohol 3:185-191.
85. Pinazo-Duran MD, Valles S, Guerri C, Renau-Piqueras J. 1996. Gestational ethanol-induced changes in protein expression during the morphogenesis of the rat optic nerve. Int J Dev Biol Suppl 1:141S-142S.
86. Pinazo-Duran MD, Renau-Piqueras J, Guerri C. 1993. Developmental changes in the optic nerve related to ethanol consumption in pregnant rats: Analysis of the ethanol-exposed optic nerve. Teratology 48:305-322.
87. Plawecki MH, DeCarlo RA, Ramchandani VA, O'Connor S. 2004. Estimation of ethanol infusion profile to produce specified BrAC time course using physiologically-based pharmacokinetic (PBPK models. Conf Proc IEEE Eng Med Biol Soc 1:778-781.
88. Plawecki MH, Decarlo R, Ramchandani VA, O'Connor S. 2007. Improved transformation of morphometric measurements for a priori parameter estimation in a physiologically-based pharmacokinetic model of ethanol. Biomed Signal Process Control 2:97-110.
89. Pons S, Zanón-Moreno V, Melo P, Vila V, Gallego-Pinazo R, Pinazo-Durán MD. 2007. [Optic neuropathy induced by prenatal drug or alcohol exposure]. Arch Soc Esp Oftalmol 82:21-26.
90. Quertemont E, Green HL, Grant KA. 2003. Brain ethanol concentrations and ethanol discrimination in rats: Effects of dose and time. Psychopharmacology (Berl) 168:262-270.
91. Räihä NC, Koskinen M, Pikkarainen P. 1967. Developmental changes in alcohol-dehydrogenase activity in rat and guinea-pig liver. Biochem J 103:623-626.
92. Rainey PM. 1993. Relation between serum and whole-blood ethanol concentrations. Clin Chem 39:2288-2292.
93. Rodriguez C, Mahle D, Gearhart J, Mattie D, Lipscomb J, Cook R, Barton H. 2007. Predicting age-appropriate pharmacokinetics of six volatile organic compounds in the rat utilizing physiologicallybased pharmacokinetic modeling. Toxicol Sci 98:43-56.
94. Roine R. 2000. Interaction of prandial state and beverage concentration on alcohol absorption. Alcohol Clin Exp Res 24:411-412.
95. Roine RP, Gentry RT, Lim RT Jr, Baraona E, Lieber CS. 1991. Effect of concentration of ingested ethanol on blood alcohol levels. Alcohol Clin Exp Res 15:734-738.
96. Ronis MJ, Korourian S, Blackburn ML, Badeaux J, Badger TM. 2010. The role of ethanol metabolism in development of alcoholic steatohepatitis in the rat. Alcohol 44:157-169.
97. Ryabinin AE, Cole M, Bloom FE, Wilson MC. 1995. Exposure of neonatal rats to alcohol by vapor inhalation demonstrates specificity of microcephaly and Purkinje cell loss but not astrogliosis. Alcohol Clin Exp Res 19:784-791.
98. Savage DD, Becher M, de la Torre AJ, Sutherland RJ. 2002. Dosedependent effects of prenatal ethanol exposure on synaptic plasticity and learning in mature offspring. Alcohol Clin Exp Res 26:1752-1758.
99. Scarino A, Tardif R, Charbonneau M. 2009. Influence of ALDH2 polymorphism on ethanol kinetics and pulmonary effects in male and female rats exposed to ethanol vapors. Inhal Toxicol 21:193-199.
100. Seitz HK, Pöschl G. 1997. The role of gastrointestinal factors in alcohol metabolism. Alcohol Alcohol 32:543-549.
101. Sharkawi M. 1984. In vivo inhibition of liver alcohol dehydrogenase by ethanol administration. Life Sci 35:2353-2357.
102. Strömland K, Pinazo-Durán MD. 2002. Ophthalmic involvement in the fetal alcohol syndrome: Clinical and animal model studies. Alcohol Alcohol 37:2-8.
103. Strubelt O, Siegers CP, Breining H. 1974. Comparative study of the absorption, elimination and acute hepatotoxic action of ethanol in guinea pigs and rats. Arch Toxicol 32:83-95.
104. Stulcová B. 1977. Postnatal development of cardiac output distribution measured by radioactive microspheres in rats. Biol Neonate 32:119-124.
105. Sultatos LG, Pastino GM, Rosenfeld CA, Flynn EJ. 2004. Incorporation of the genetic control of alcohol dehydrogenase into a physiologically based pharmacokinetic model for ethanol in humans. Toxicol Sci 78:20-31.
106. Umulis DM, Gürmen NM, Singh P, Fogler HS. 2005. A physiologically based model for ethanol and acetaldehyde metabolism in human beings. Alcohol 35:3-12.
107. Weissenborn R, Duka T. 2003. Acute alcohol effects on cognitive function in social drinkers: Their relationship to drinking habits Psychopharmacology (Berl) 165:306-312.
108. West JR, Goodlett CR, Bonthius DJ, Pierce DR. 1989. Manipulating peak blood alcohol concentrations in neonatal rats: Review of an animal model for alcohol-related developmental effects. Neurotoxicology 10:347-365.
109. Wilkinson PK, Sedman AJ, Sakmar E, Kay DR, Wagner JG. 1977 Pharmacokinetics of ethanol after oral administration in the fasting state. J Pharmacokinet Biopharm 5:207-224.
110. Winek CL, Carfagna M. 1987. Comparison of plasma, serum, and whole blood ethanol concentrations. J Anal Toxicol 11:267-268.
111. Yoon M, Nong A, Clewell HJ 3rd, Taylor MD, Dorman DC, Andersen ME. 2009a. Lactational transfer of manganese in rats: Predicting manganese tissue concentration in the dam and pups from inhalation exposure with a pharmacokinetic model. Toxicol Sci 112:23-43.
112. Yoon M, Nong A, Clewell HJ 3rd, Taylor MD, Dorman DC, Andersen ME.2009b. Evaluating placental transfer and tissue concentrations of manganese in the pregnant rat and fetuses after inhalation exposures with a PBPK model. Toxicol Sci 112:44-58.
113. Zorzano A, Herrera E. 1989. Disposition of ethanol and acetaldehyde in late pregnant rats and their fetuses. Pediatr Res 25:102-106.