Your prodrug releases formaldehyde: Should you be concerned? No!

Journal of Pharmaceutical Sciences

Volumn 97, Issue 10, 2008, Pages 4184-4193

  Dhareshwar, Sundeep S ^a,b   Stella, Valentino J ^a  

^a UNIVERSITY OF KANSAS   (United States)

^b NOVARTIS PHARMA AG   (Switzerland)

Author keywords

Apparent toxicity; Formaldehyde release; In vivo metabolism; Prodrugs

Indexed keywords

ADEFOVIR DIPIVOXIL; CEFDITOREN PIVOXIL; FORMALDEHYDE; FORMIC ACID; FOSPHENYTOIN SODIUM; FOSPROPOFOL; GLUTATHIONE; GUAIFENESIN; IMATINIB; PRODRUG; TENOFOVIR DISOPROXIL; VENLAFAXINE;

DETOXIFICATION; DRUG FORMULATION; DRUG METABOLISM; DRUG RELEASE; DRUG TRANSFORMATION; ENVIRONMENTAL EXPOSURE; HUMAN; NONHUMAN; NOTE;

EID: 55749109196     PISSN: 00223549     EISSN: 15206017     Source Type: Journal    
DOI: 10.1002/jps.21319     Document Type: Note

References (69)

1. Atkinson R. 1990. Gas-phase tropospheric chemistry of organic compounds: A review. Atmos Environ 24A:1-41.
2. Kirchstetter TW, Singer BC, Harley RA, Kendall GR, Chan W. 1996. Impact of oxygenated gasoline use on California light-duty vehicle emissions. Environ Sci Technol 30:661-670.
3. Maejima K, Suzuki T, Niwa K, Numata H, Maekawa A, Nagase S, Ishinishi N. 1992. Toxicity to rats of methanol-fueled engine exhaust inhaled continuously for 28 days. J Toxicol Environ Health 37:293-312.
4. Brown SK. 1999. Chamber assessment of formaldehyde and VOC emissions from wood-based panels. Indoor Air 9:209-215.
5. WHO. 1989. Formaldehyde (Environmental Health Criteria 89). International Programme on Chemical Safety. Geneva: WHO.
6. Kuykendall JR, Trela BA, Bogdanffy MS. 1995. DNA-protein crosslink formation in rat nasal epithelial cells by hexamethylphosphoramide and its correlation with formaldehyde production. Mutat Res 343:209-218.
7. El-Rashidy R, Niazi S. 1983. A new metabolite of butylated hydroxyanisole in man. Biopharm Drug Dispos 4:389-396.
8. Vree TB, Verwey-van Wissen CPWGM. 1992. Pharmacokinetics and metabolism of codeine in humans. Biopharm Drug Dispos 13:445-460.
9. Partanen T. 1993. Formaldehyde exposure and respiratory cancer - a meta-analysis of the epidemiologic evidence. Scand J Work Environ Health 19:8-15.
10. Hauptmann M, Lubin JH, Stewart PA, Hayes RB, Blair A. 2004. Mortality from solid cancers among workers in formaldehyde industries. Am J Epidemiol 159:1117-1130.
11. Marsh GM, Youk AO, Buchanich JM, Cassidy LD, Lucas LJ, Esmen NA, Gathuru IM. 2002. Pharyngeal cancer mortality among chemical plant workers exposed to formaldehyde. Toxicol Ind Health 18:257-268.
12. Collins JJ, Acquavella JF, Esmen NA. 1997. An updated meta-analysis of formaldehyde exposure and upper respiratory tract cancers. J Occup Environ Med 39:639-651.
13. Marsh GM, Youk AO, Buchanich JM, Erdal S, Esmen NA. 2007. Work in the metal industry and nasopharyngeal cancer mortality among formaldehyde-exposed workers. Regul Toxicol Pharm 48:308-319.
14. Arts JHE, Rennen MAJ, de Heer C. 2006. Inhaled formaldehyde: Evaluation of sensory irritation in relation to carcinogenicity. Regul Toxicol Pharm 44:144-160.
15. Liteplo RG, Meek ME. 2003. Inhaled formaldehyde: Exposure estimation, hazard characterization, and exposure-response analysis. J Toxicol Environ Health B Crit Rev 6:85-114.
16. Brown SK. 1999. Chamber assessment of formaldehyde and VOC emissions from wood-based panels. Indoor Air 9:209-215.
17. Mansfield CT, Hodge BT, Hege RB, Hamlin WC. 1977. Analysis of formaldehyde in tobacco smoke by high performance liquid chromatography. J Chromatogr Sci 15:301-302.
18. U.S. Environmental Protection Agency. 1988. Recommendations for and documentation of biological values for use in risk assessment. Washington, DC: U.S. Environmental Protection Agency. EPA/600/6-87/008 (NTIS PB88179874).
19. Weber-Tschopp A, Fischer T, Grandjean E. 1977. Reizwirkung des formaldehyds (HCHO) auf den menschen. Int Arch Occup Environ Health 39:207-218.
20. Andersen I, Molhave L. 1983. Controlled human studies with formaldehyde. In: Gibson JE, editor. Formaldehyde toxicity. Washington, DC: Hemisphere. pp. 154-165.
21. Bender JR, Mullin LS, Graepel GJ, Wilson WE. 1983. Eye irritation response of humans to formaldehyde. Am Ind Hyg Assoc J 44:463-465.
22. Kulle TJ, Sauder LR, Hebel JR, Green DJ, Chatham MD. 1987. Formaldehyde dose-response in healthy non-smokers. J Air Pollut Control Assoc 37:919-924.
23. 2O under controlled conditions. Am Ind Hyg Assoc J 46:1-3.
24. Bernstein RS, Stayner LT, Elliott LJ, Kimbrough R, Falk H, Blade L. 1984. Inhalation exposure to formaldehyde: An overview of its toxicology, epidemiology, monitoring, and control. Am Ind Hyg Assoc J 45:778-785.
25. Franks SJ. 2005. A mathematical model for the absorption and metabolism of formaldehyde vapour by humans. Toxicol Appl Pharm 206:309-320.
26. Casanova M, Deyo DF, Heck HD. 1989. Covalent binding of inhaled formaldehyde to DNA in the nasal mucosa of Fischer 344 rats: Analysis of formaldehyde and DNA by high-performance liquid chromatography and provisional pharmacokinetic interpretation. Fundam Appl Toxicol 12:397-417.
27. Lindinger W, Taucher J, Jordan A, Hansel A, Vogel W. 1997. Endogenous production of methanol after the consumption of fruit. Alcohol Clin Exp Res 21:939-943.
28. Monte WC. 1984. Aspartame: Methanol and the public health. J Appl Nutr 36:42-54.
29. Greizerstein HB. 1981. Congener contents of alcoholic beverages. J Stud Alcohol 42:1030-1037.
30. Davoli E, Cappellini L, Airoldi L, Fanelli R. 1986. Serum methanol concentrations in rats and in men after a single dose of aspartame. Food Chem Toxicol 24:187-189.
31. Medinsky MA, Dorman DC. 1994. Assessing risks of low-level methanol exposure. CIIT Act 14:1-7.
32. ACGIH. 2000. Threshold limit values for chemical substances and physical agents and biological exposure indices. Cincinnati, OH: American Conference of Governmental Industrial Hygienists.
33. d'Alessandro A, Osterloh JD, Chuwers P, Quinlan PJ, Kelly TJ, Becker CE. 1994. Formate in serum and urine after controlled methanol exposure at the threshold limit value. Environ Health Perspect 102:178-181.
34. Franzblau A, Lee EW, Schreck RM, D'Arch JB, Santorock J, Levine SP. 1993. Absence of formic acid accumulation in urine following five days of methanol exposure. Appl Occup Environ Hyg 10:883-888.
35. Osterloh JD, d'Alessandro A, Chuwers P, Mogadeddi H, Kelly TJ. 1996. Serum concentrations of methanol after inhalation at 200 ppm. J Occup Environ Med 38:571-576.
36. Batterman SA, Franzblau A, D'Arch JB, Sargent NE, Gross KB, Schreck RM. 1998. Breath, urine, and blood measurements as biological exposure indices of short-term inhalation exposure to methanol. Int Arch Occup Environ Health 71:325-335.
37. Sedivec V, Mraz M, Flek J. 1981. Biological monitoring of persons exposed to methanol vapors. Int Arch Occup Environ Health 48:257-271.
38. Ernstgard L, Shibata E, Johanson G. 2005. Uptake and disposition of inhaled methanol vapor in humans. Toxicol Sci 88:30-38.
39. Restani P, Galli CL. 1991. Oral toxicity of formaldehyde and its derivatives. Crit Rev Toxicol 21:315-378.
40. Casanova-Schmitz M, Heck HD, Everitt JI, Harrington WW, Jr., Popp JA. 1988. Formaldehyde concentrations in the blood of rhesus monkeys after inhalation exposure. Food Chem Toxicol 26:715-716.
41. 14C] formaldehyde in rats after inhalation exposure. In: Gibson JE, editor. Formaldehyde toxicity. Washington, DC: Hemisphere. pp. 26-37.
42. Eells JT, McMartin KE, Black K, Virayotha V, Tisdell RH, Tephly TR. 1981. Formaldehyde poisoning. Rapid metabolism to formic acid. JAMA 246:1237-1238.
43. Burkhart KK, Kulig KW, McMartin KE. 1990. Formate levels following a formalin ingestion. Vet Hum Toxicol 32:135-137.
44. 3H] formaldehyde. Toxicol Appl Pharmacol 76:26-44.
45. Uotila L, Koivusalo M. 1974. Formaldehyde dehydrogenase from human liver. Purification, properties, and evidence for the formation of glutathione thiol esters by the enzyme. J Biol Chem 249:7653-7663.
46. Hantson P, Haufroid V, Wallemacq P. 2005. Formate kinetics in methanol poisoning. Hum Exp Toxicol 24:55-59.
47. Osterloh JD, Pond SM, Grady S, Becker CE. 1986. Serum formate concentrations in methanol intoxication as a criterion for hemodialysis. Ann Intern Med 104:200-203.
48. Kerns WN, Tomaszewski C, McMartin KE, Ford M, Brent J. 2002. Formate kinetics in methanol poisoning. J Toxicol Clin Toxicol 40:137-143.
49. Thrasher JD, Kilburn KH. 2001. Embryo toxicity and teratogenicity of formaldehyde. Arch Environ Health 56:300-311.
50. McMartin KE, Martin-Amat G, Noker PE, Tephly TR. 1979. Lack of a role for formaldehyde in methanol poisoning in the monkey. Biochem Pharmacol 28:645-649.
51. Rietbrock N. 1969. Kinetics and pathways of methanol metabolism. Naunyn Schmiedebergs Arch Exp Pathol Pharmakol 263:88-105.
52. Cascieri TC, Clary JJ. 1992. Formaldehyde-oral toxicity assessment. Comments Toxicol 4:295-304.
53. Owen BA, Dudney CS, Tan EL, Easterly CE. 1990. Formaldehyde in drinking water: Comparative hazard evaluation and an approach to regulation. Regul Toxicol Pharmacol 11:220-236.
54. Testa B, Mayer JM. 2003. Hydrolysis in drug and rodrug metabolism: Chemistry, biochemistry, and enzymology. Weinheim, Germany: Wiley-VCH GmbH. p. 780.
55. Stella VJ, Borchardt RT, Hageman MJ, Oliyai R, Maag H, Tilley J. 2007. Prodrugs: Challenges and rewards. USA: AAPS Press/Springer. p. 730.
56. Safadi M, Oliyai R, Stella VJ. 1993. Phosphoryloxymethyl carbamates and carbonates-novel water-soluble prodrugs for amines and hindered alcohols. Pharm Res 10:1350-1355.
57. Vyas DM, Wong H, Crosswell AR, Casazza AM, Knipe J, Mamber SW, Doyle TW. 1993. Synthesis and antitumor evaluation of water soluble taxol phosphates. Bioorg Med Chem Lett 3:1357-1360.
58. Heck HdA, Casanova M, Starr TB. 1990. Formaldehyde toxicity. New understanding. Crit Rev Toxicol 20:397-426.
59. +-dependent dehydrogenases in rat nasal mucosal homogenates. Biochem Pharmacol 33:1137-1142.
60. Bolt HM. 1987. Experimental toxicology of formaldehyde. J Cancer Res Clin Oncol 113:305-309.
61. WHO. 2000. Air quality guidelines for Europe, 2nd edition. Copenhagen: World Health Organization regional office for Europe. WHO Regional Publications, European Series No. 91, p. 288.
62. Florence E, Milner DF. 1981. Determination of free and loosely protein-bound formaldehyde in the tissues of pigs fed formalin-treated skim milk as a protein supplement. J Sci Food Agric 32:288-292.
63. Bianchi F, Careri M, Musci M, Mangia A. 2007. Fish and food safety: Determination of formaldehyde in 12 fish species by SPME extraction and GC-MS analysis. Food Chem 100:1049-1053.
64. Radford T, Dalsis DE. 1982. Analysis of formaldehyde in shrimp by HPLC. J Agric Food Chem 30:600-602.
65. Tsuchiya K, Hayashi Y, Onodera M, Hasegawa T. 1975. Toxicity of formaldehyde in experimental animals-concentrations of the chemical in the elution from dishes of formaldehyde resin in some vegetables. Keio J Med 24:19-37.
66. Kaminski J, Atwal AS, Mahadevan S. 1993. Determination of formaldehyde in fresh and retail milk by liquid column chromatography. J Assoc Off Anal Chem Int 76:1010-1013.
67. Baraniak Z, Nagpal DS, Neidert E. 1988. Gas chromatographic determination of formaldehyde in maple as 2,4-dinitrophenylhydrazone derivative. J Assoc Off Anal Chem 71:740-741.
68. Hayashi T, Reece CA, Shibamoto T. 1986. Gas chromatographic determination of formaldehyde in coffee via thiazolidine derivative. J Assoc Off Anal Chem 69:101-105.
69. Burini G, Coli R. 2004. Determination of formaldehyde in spirits by high-performance liquid chromatography with diode-array detection after derivatization. Anal Chim Acta 511:155-158.