Effect of obesity on the pharmacokinetics of drugs in humans

Clinical Pharmacokinetics

Volumn 49, Issue 2, 2010, Pages 71-87

  Hanley, Michael J ^a   Abernethy, Darrell R ^b   Greenblatt, David J ^a  

^a TUFTS UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b UNITED STATES PHARMACOPEIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALBUMIN; ARGATROBAN; BUSULFAN; CARBOPLATIN; CIPROFLOXACIN; CISATRACURIUM; CISPLATIN; CYCLOPHOSPHAMIDE; CYTOCHROME P450 2E1; DALTEPARIN; DAPTOMYCIN; DOCETAXEL; DOXORUBICIN; DROTRECOGIN; ENOXAPARIN; ERTAPENEM; ETOPOSIDE; GLIMEPIRIDE; HEPARIN; IRINOTECAN; LINEZOLID; OROSOMUCOID; PACLITAXEL; PIPERACILLIN PLUS TAZOBACTAM; ROCURONIUM; SITAGLIPTIN; THIOTEPA; TINZAPARIN; TOPOTECAN; UNINDEXED DRUG;

ANTICOAGULANT THERAPY; BLOOD CLOTTING; BODY COMPOSITION; BODY FAT; BODY HEIGHT; BODY MASS; BODY SURFACE; BODY WEIGHT; BREAST METASTASIS; CELLULITIS; CLINICAL TRIAL; COMORBIDITY; DISTRIBUTION VOLUME; DRUG BINDING; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG CONJUGATION; DRUG DISPOSITION; DRUG HALF LIFE; DRUG MEGADOSE; DUAL ENERGY X RAY ABSORPTIOMETRY; ENZYME ACTIVITY; GLOMERULUS FILTRATION; HEART FUNCTION; HEPARIN INDUCED THROMBOCYTOPENIA; HODGKIN DISEASE; HUMAN; IMPEDANCE; KIDNEY TUBULE ABSORPTION; KIDNEY TUBULE EXCRETION; LEAN BODY WEIGHT; LIPOPHILICITY; MAINTENANCE DRUG DOSE; NON INSULIN DEPENDENT DIABETES MELLITUS; OBESITY; PHYSICAL CHEMISTRY; PLASMA CONCENTRATION-TIME CURVE; PLETHYSMOGRAPHY; PREDICTION; PREVALENCE; PRIORITY JOURNAL; PROTEIN BINDING; REVIEW; SINGLE DRUG DOSE; SKINFOLD THICKNESS; TISSUE BLOOD FLOW; TISSUE STRUCTURE;

ANTI-BACTERIAL AGENTS; ANTICOAGULANTS; ANTINEOPLASTIC AGENTS; BODY COMPOSITION; BODY WEIGHTS AND MEASURES; HUMANS; HYPOGLYCEMIC AGENTS; NEUROMUSCULAR BLOCKING AGENTS; OBESITY; PRESCRIPTION DRUGS;

EID: 74249120678     PISSN: 03125963     EISSN: 11791926     Source Type: Journal    
DOI: 10.2165/11318100-000000000-00000     Document Type: Review

References (96)

1. Kelly T, Yang W, Chen CS, et al. Global burden of obesity in 2005 and pro-jections to 2030. Int J Obes 2008; 32: 1431-1437
2. Yach D, Stuckler D, Brownell KD. Epidemiologic and economic consequences of the global epidemics of obesity and diabetes. Nat Med 2006; 12: 62-66
3. World Health Organization. Obesity and overweight [fact sheet no. 311; online]. Available from URL: http://www.who.int/mediacentre/factsheets/ fs311/en/index.html [Accessed 2009 Sep 29]
4. Lobstein T, Baur L, Uauy R. Obesity in children and young people: a crisis in public health. Obes Rev 2004; 5 Suppl. 1: 4-85
5. World Health Organization. Information sheet on obesity and overweight [online]. Available from URL: http://www.who.int/dietphysicalactivity/ publications/facts/obesity/en/ [Accessed 2009 Sep 29] Haslam DW, James WP. Obesity. Lancet 2005; 366: 1197-209
6. Hossain P, Kawar B, El Nahas M. Obesity and diabetes in the developing world: a growing challenge. N Engl J Med 2007; 356: 213-215
7. Abernethy DR, Greenblatt DJ. Drug disposition in obese humans: an update. Clin Pharmacokinet 1986; 11: 199-213
8. Blouin RA, Warren GW. Pharmacokinetic considerations in obesity. J Pharm Sci 1999; 88: 1-7
9. Cheymol G. Effects of obesity on pharmacokinetics implications for drug therapy. Clin Pharmacokinet 2000; 39: 215-231
10. Abernethy DR, Greenblatt DJ. Pharmacokinetics of drugs in obesity. Clin Pharmacokinet 1982; 7: 108-124
11. Cheymol G. Clinical pharmacokinetics of drugs in obesity: an update. Clin Pharmacokinet 1993; 25: 103-114
12. Bearden DT, Rodvold KA. Dosage adjustments for antibacterials in obese patients: applying clinical pharmacokinetics. Clin Pharmacokinet 2000; 38: 415-426
13. Green B, Duffull SB. What isthe best size descriptor to use for pharmacokinetic studies in the obese? Br J Clin Pharmacol 2004; 58: 119-133
14. Ellis KJ. Human body composition: in vivo methods. Physiol Rev 2000; 80: 649-680
15. Fields DA, Goran MI, McCrory MA. Body-composition assessment via air-displacement plethysmography in adults and children: a review. Am J Clin Nutr 2002; 75: 453-467
16. Gray DS, Bray GA, Bauer M, et al. Skinfold thickness measurements in obese subjects. Am J Clin Nutr 1990; 51: 571-577
17. Kyle UG, Bosaeus I, De Lorenzo AD, et al. Bioelectrical impedance analysis: part I. Review of principles and methods. Clin Nutr 2004; 23: 1226-1243 (Pubitemid 39243041)
18. Sutcliffe JF. A review of in vivo experimental methods to determine the com-position of the human body. Phys Med Biol 1996; 41: 791-833
19. Pietrobelli A, Formica C, Wang Z, et al. Dual-energy X-ray absorptiometry body composition model: review of physical concepts. Am J Physiol 1996; 271: E941-51
20. World Health Organization. Obesity: preventing and managing the global epidemic. Report of a WHO Consultation [WHO technical report no. 894; online]. Available from URL: http://whqlibdoc.who.int/trs/WHO-TRS-894.pdf [Accessed 2009 Sep 29]
21. Du Bois D, Du Bois EF. Clinical calorimetry: tenth paper. A formula to esti-mate the approximate surface area ifheight and weight be known. Arch Intern Med 1916; 17: 863
22. Mosteller RD. Simplified calculation of body-surface area. N Engl J Med 1987; 317: 1098
23. Field KM, Kosmider S, Jefford M, et al. Chemotherapy dosing strategies in the obese, elderly, and thin patient: results of a nationwide survey. J Oncol Pract 2008; 4: 108-13 Devine BJ. Gentamicin therapy. Drug Intell Clin Pharm 1974; 8: 650-5
24. Janmahasatian S, Duffull SB, Ash S, et al. Quantification of lean body weight. Clin Pharmacokinet 2005; 44: 1051-1065
25. Green B, Duffull SB. Caution when lean body weight isused as asize descriptor for obese subjects. Clin Pharmacol Ther 2002; 72: 743-744
26. Han PY, Duffull SB, Kirkpatrick CM, et al. Dosing in obesity: a simple solution to a big problem. Clin Pharmacol Ther 2007; 82: 505-508
27. Duffull SB, Dooley MJ, Green B, et al. A standard weight descriptor for dose adjustment in the obese patient. Clin Pharmacokinet 2004; 43: 1167-1178
28. Rivlin RS. Keeping the young-elderly healthy: is it too late to improve our health through nutrition? Am J Clin Nutr 2007; 86: 1572-6S
29. Han PY, Duffull SB, Kirkpatrick CMJ, et al. Response to "influence of lean body weightonanticancer drug clearance" [letter]. Clin Pharmacol Ther 2009; 85: 24 Niazi S. Volume of distribution as a function of time. J Pharm Sci 1976; 65: 452-4
30. Greenblatt DJ, Abernethy DR, Divoll M. Is volume of distribution at steady state a meaningful kinetic variable. J Clin Pharmacol 1983; 23: 391-400
31. Hollenstein UM, Brunner M, Schmid R, et al. Soft tissue concentrations of ciprofloxacin in obese and lean subjects following weight adjusted dosing. Int J Obes Relat Metab Disord 2001; 25: 354-358
32. Jansson PA, Larsson A, Lonnroth PN. Relationship between blood pressure, metabolic variables, and blood flow in obese subjects with or without non-insulin-dependent diabetes mellitus. Eur J Clin Invest 1998; 28: 813-818
33. Summers LK, Samra JS, Humphreys SM, et al. Subcutaneous abdominal adipose tissue blood flow: variation within and between subjects and relationship to obesity. Clin Sci 1996; 91: 679-683
34. Abel ED, Litwin SE, Sweeney G. Cardiac remodeling in obesity. Physiol Rev 2008; 88: 389-419
35. Abernethy DR, Greenblatt DJ, Divoll M, et al. The influence of obesity on the pharmacokinetics of oral alprazolam and triazolam. Clin Pharmacokinet 1984; 9: 177-183
36. Abernethy DR, Greenblatt DJ. Phenytoin disposition in obesity: determina-tion of loading dose. Arch Neurol 1985; 42: 468-471
37. Benedek IH, Fiske III WD, Griffen WO. Serum alpha 1-acid glycoprotein and the binding of drugs in obesity. Br J Clin Pharmacol 1983; 16: 751-754
38. Benedek IH, Blouin RA, McNamara PJ. Serum protein binding and the role of increased alpha 1-acid glycoprotein in moderately obese male subjects. Br J Clin Pharmacol 1984; 18: 941-946
39. Cheymol G. Comparative pharmacokinetics of intravenous propranolol in obese and normal volunteers. J Clin Pharmacol 1987; 27: 874-879
40. Derry CL, Kroboth PD, Pittenger AL, et al. Pharmacokinetics and pharma-codynamics of triazolam after two intermittent doses in obese and normal weight men. J Clin Psychopharmacol 1995; 15: 197-205
41. Saadeh S. Nonalcoholic fatty liver disease and obesity. Nutr Clin Pract 2007; 22: 1-10
42. Ijaz S, Yang W, Winslet MC, et al. Impairment of hepatic microcirculation in fatty liver. Microcirculation 2003; 10: 447-456
43. O'Shea D, Davis SN, Kim RB, et al. Effect of fasting and obesity in humans on the 6-hydroxylation of chlorzoxazone: a putative probe of CYP2E1 activity. Clin Pharmacol Ther 1994; 56: 359-367
44. Emery MG, Fisher JM, Chien JY, et al. CYP2E1 activity before and after weight loss in morbidly obese subjects with nonalcoholic fatty liver disease. Hepatology 2003; 38: 428-435
45. Abernethy DR, Greenblatt DJ, Divoll M, et al. Enhanced glucoronide conjugation of drugs in obesity: studies of lorazepam, oxazepam, and acetaminophen. J Lab Clin Med 1983; 101: 873-880
46. Abernethy DR, Divoll M, Greenblatt DJ, et al. Obesity, sex, and acet-aminophen disposition. Clin Pharmacol Ther 1982; 31: 783-790
47. Pai MP, Norenberg JP, Anderson T, et al. Influence of morbid obesity on the single-dose pharmacokinetics of daptomycin. Antimicrob Agents Chemother 2007; 51: 2741-2747
48. Mathijssen RH, Sparreboom A. Influence of lean body weight on anticancer drug clearance. Clin Pharmacol Ther 2009; 85: 23-24
49. Abernethy DR, Greenblatt DJ, Divoll M, et al. Prolonged accumulation of diazepam in obesity. J Clin Pharmacol 1983; 23: 369-376
50. Abernethy DR, Greenblatt DJ, Divoll M, et al. Prolongation of drug half-life due to obesity: studiesof desmethyldiazepam (clorazepate). J Pharm Sci 1982; 71: 942-944
51. Dvorchik BH, Damphousse D. The pharmacokinetics of daptomycin in moderately obese, morbidly obese, and matched nonobese subjects. J Clin Pharmacol 2005; 45: 48-56
52. Benvenuto M, Benziger DP, Yankelev S, et al. Pharmacokinetics and toler-ability of daptomycin at doses up to 12 milligrams per kilogram of body weight once daily in healthy volunteers. Antimicrob Agents Chemother 2006; 50: 3245-3249
53. Dandekar PK, Tessier PR, Williams P, et al. Pharmacodynamic profile of daptomycin against Enterococcus species and methicillin-resistant Staphy-lococcus aureus in a murine thigh infection model. J Antimicrob Chemother 2003; 52: 405-411
54. Louie A, Kaw P, Liu W, et al. Pharmacodynamics of daptomycin in a murine thigh model of Staphylococcus aureus infection. Antimicrob Agents Chemo-ther 2001; 45: 845-851
55. Safdar N, Andes D, Craig WA. In vivo pharmacodynamic activity of dapto-mycin. Antimicrob Agents Chemother 2004; 48: 63-68
56. Chen M, Nafziger AN, Drusano GL, et al. Comparative pharmacokinetics and pharmacodynamic target attainment of ertapenem in normal weight, obese, and extremely obese adults. Antimicrob Agents Chemother 2006; 50: 1222-1227
57. Allard S, Kinzig M, Boivin G, et al. Intravenous ciprofloxacin disposition in obesity. Clin Pharmacol Ther 1993; 54: 368-373
58. Newman D, Scheetz MH, Adeyemi OA, et al. Serum piperacillin/tazobactam pharmacokinetics in a morbidly obese individual. Ann Pharmacother 2007; 41: 1734-1739
59. Stein GE, Schooley SL, Peloquin CA, et al. Pharmacokinetics and pharma-codynamics of linezolid in obese patients with cellulitis. Ann Pharmacother 2005; 39: 427-432
60. Mersfelder TL, Smith CL. Linezolid pharmacokinetics in an obese patient. Am J Health Syst Pharm 2005; 62: 464-467
61. MacGowan AP. Pharmacokinetic and pharmacodynamic profile oflinezolid in healthy volunteers and patients with Gram-positive infections. J Antimicrob Chemother 2003; 51 Suppl. 2: ii17-25
62. Hendershot PE, Antal EJ, Welshman IR, et al. Linezolid: pharmacokinetic and pharmacodynamic evaluation of coadministration with pseudoephedrine HCl, phenylpropanolamine HCl, and dextromethorpan HBr. J Clin Pharmacol 2001; 41: 563-572
63. Burkhardt O, Borner K, von der Hoh N, et al. Single-and multiple-dose pharmacokinetics oflinezolid and co-amoxiclav in healthy human volunteers. J Antimicrob Chemother 2002; 50: 707-712
64. Rice L, Hursting MJ, Baillie GM. Argatroban anticoagulation in obese versus nonobese patients: implications for treating heparin-induced thrombocyto-penia. J Clin Pharmacol 2007; 47: 1028-1034
65. Weitz JI. Low-molecular-weight heparin. N Engl J Med 1997; 337: 688-698
66. Sanderink GJ, Liboux AL, Jariwala N, et al. The pharmacokinetics and pharmacodynamics of enoxaparin in obese volunteers. Clin Pharmacol Ther 2002; 72: 308-318
67. Hainer JW, Barrett JS, Assaid CA, et al. Dosing in heavy-weight/obese patients with LMWH, tinzaparin: a pharmacodynamic study. Thromb Haemost 2002; 87: 817-823
68. Bazinet A, Almanric K, Brunet C, et al. Dosage of enoxaparin among obese and renal impairment patients. Thromb Res 2005; 116: 41-50
69. Green B, Duffull SB. Development of a dosing strategy for enoxaparin in obese patients. Br J Clin Pharmacol 2003; 56: 96-103
70. Yee JY, Duffull SB. The effect of body weight on dalteparin pharmacokinetics: a preliminary study. Eur J Clin Pharmacol 2000; 56: 293-297
71. Shukla UA, Chi EM, Lehr KH. Glimepiride pharmacokinetics in obese versus non-obese diabetic patients. Ann Pharmacother 2004; 38: 30-35
72. Herman GA, Bergman A, Liu F, et al. Pharmacokinetics and pharmaco-dynamic effects of the oral DPP-4 inhibitor sitagliptin in middle-aged obese subjects. J Clin Pharmacol 2006; 46: 876-886
73. Herman GA, Stevens CS, Van Dyck K, et al. Pharmacokinetics and pharma-codynamics of sitagliptin, an inhibitor of dipeptidyl peptidase IV, in healthy subjects: results from two randomized, double-blind, placebo-controlled studies with single oral doses. Clin Pharmacol Ther 2005; 78: 675-688
74. Bergman AJ, Stevens C, Zhou Y, et al. Pharmacokinetic and pharmaco-dynamic properties of multiple oral doses of sitagliptin, a dipeptidyl pepti-dase-IV inhibitor: a double-blind, randomized, placebo-controlled study in healthy male volunteers. Clin Ther 2006; 28: 55-72
75. Sparreboom A, Wolff AC, Mathijssen RH, et al. Evaluation of alternate size descriptors for dose calculation of anticancer drugs in the obese. J Clin Oncol 2007; 25: 4707-4713
76. Gibbs JP, Gooley T, Corneau B, et al. The impact of obesity and disease on busulfan oral clearance in adults. Blood 1999; 93: 4436-4440
77. Nguyen L, Leger F, Lennon S, et al. Intravenous busulfan in adults prior to haematopoietic stem cell transplantation: a population pharmacokinetic study. Cancer Chemother Pharmacol 2006; 57: 191-198
78. Ritzmo C, Soderhall S, Karlen J, et al. Pharmacokinetics of doxorubicin and etoposide in a morbidly obese pediatric patient. Pediatr Hematol Oncol 2007; 24: 437-445
79. PalmC, Bjork O, Bjorkholm M, etal. Quantification of doxorubicin inplasma: a comparative study of capillary and venous blood sampling. Anticancer Drugs 2001; 12: 859-864
80. Eksborg S, Palm C, Bjork O. A comparative pharmacokinetic study of doxorubicin and 4'-epi-doxorubicin in children with acute lymphocytic leukemia using a limited sampling procedure. Anticancer Drugs 2000; 11: 129-136
81. Eksborg S, Soderhall S, Frostvik-Stolt M, et al. Plasma pharmacokinetics of etoposide (VP-16) after IV administration to children. Anticancer Drugs 2000; 11: 237-241
82. de Jonge ME, Mathot RA, van Dam SM, et al. Extremely high exposures in an obese patient receiving high-dose cyclophosphamide, thiotepa, and carbo-platin. Cancer Chemother Pharmacol 2002; 50: 251-255
83. Rosner GL, Hargis JB, Hollis DR, et al. Relationship between toxicity and obesity in women receiving adjuvant chemotherapy for breast cancer: results from cancer and leukemia group B study 8541. J Clin Oncol 1996; 14: 3000-3008
84. Leykin Y, Pellis T, Lucca M, et al. The effects of cisatracurium on morbidly obese women. Anesth Analg 2004; 99: 1090-1094
85. Leykin Y, Pellis T, Lucca M, et al. The pharmacodynamic effects of rocur-onium when dosed according to real body weight or ideal body weight in morbidly obese patients. Anesth Analg 2004; 99: 1086-1089
86. Puhringer FK, Keller C, Kleinsasser A, et al. Pharmacokinetics of rocuronium bromide in obese female patients. Eur J Anaesthesiol 1999; 16: 507-510
87. Loveland SM, Lewin JJ III, Amabile CM, et al. Obese man treated with dro-trecogin alfa (activated). Ann Pharmacother 2003; 37: 918-919
88. Small DS, Levy H. Comment: obese man treated with drotrecogin alfa (acti-vated). Ann Pharmacother 2004; 38: 722
89. Levy H, Small D, Heiselman DE, et al. Obesity does not alter the pharmaco-kinetics of drotrecogin alfa (activated) in severe sepsis. Ann Pharmacother 2005; 39: 262-267
90. Wojcicki J, Jaroszynska M, Drozdzik M, et al. Comparative pharmacokinetics and pharmacodynamics of propranolol and atenolol in normolipaemic and hyperlipidaemic obese subjects. Biopharm Drug Dispos 2003; 24: 211-218
91. Cheymol G, Poirier JM, Carrupt PA, et al. Pharmacokinetics of b-adreno-ceptor blockers in obese and normal volunteers.Br JClin Pharmacol 1997; 43: 563-570
92. Viriyayudhakorn S, Thitiarchakul S, Nachaisit S, et al. Pharmacokinetics of quinine in obesity. Trans R Soc Trop Med Hyg 2000; 94: 425-428
93. Doose DR, Wang SS, Padmanabhan M, et al. Effect of topiramate or carba-mazepine on the pharmacokinetics of an oral contraceptive containing nor-ethindrone and ethinyl estradiol in healthy obese and nonobese female subjects. Epilepsia 2003; 44: 540-549
94. Holt VL, Cushing-Haugen KL, Daling JR. Body weight and risk of oral contraceptive failure. Obstet Gynecol 2002; 99 (5 Pt 1): 820-827
95. Holt VL, Scholes D, Wicklund KG, et al. Body mass index, weight, and oral contraceptive failure risk. Obstet Gynecol 2005; 105: 46-52
96. Brunner Huber LR, Hogue CJ, Stein AD, et al. Body mass index and risk for oral contraceptive failure: a case-cohort study in South Carolina. Ann Epidemiol 2006; 16: 637-643