Effects of macrolide antibiotics on rat embryonic heart function in vitro

Birth Defects Research Part B - Developmental and Reproductive Toxicology

Volumn 101, Issue 2, 2014, Pages 189-198

  Nilsson, Mats F ^a   Webster, William S ^a,b  

^a UPPSALA UNIVERSITY   (Sweden)

^b UNIVERSITY OF SYDNEY   (Australia)

Author keywords

Embryonic cardiac function; Macrolide antibiotics; Teratogenicity

Indexed keywords

AZITHROMYCIN; CLARITHROMYCIN; ERYTHROMYCIN; ERYTHROMYCIN ETHYLSUCCINATE; ERYTHROMYCIN STEARATE; MACROLIDE; POTASSIUM CHANNEL HERG; ANTIINFECTIVE AGENT; TERATOGENIC AGENT;

ANIMAL TISSUE; ARTICLE; BRADYCARDIA; CONCENTRATION RESPONSE; CONTROLLED STUDY; DRUG EFFECT; EMBRYO; HEART FUNCTION; IN VITRO STUDY; NONHUMAN; PRIORITY JOURNAL; RAT; TERATOGENICITY; ANIMAL; CHEMICALLY INDUCED; CONGENITAL MALFORMATION; DOSE RESPONSE; DRUG EFFECTS; EMBRYO CULTURE; EMBRYOLOGY; FEMALE; HEART; HEART ARRHYTHMIA; MALE; SPRAGUE DAWLEY RAT;

ABNORMALITIES, DRUG-INDUCED; ANIMALS; ANTI-BACTERIAL AGENTS; ARRHYTHMIAS, CARDIAC; BRADYCARDIA; CLARITHROMYCIN; DOSE-RESPONSE RELATIONSHIP, DRUG; EMBRYO CULTURE TECHNIQUES; ERYTHROMYCIN; FEMALE; HEART; MACROLIDES; MALE; RATS; RATS, SPRAGUE-DAWLEY; TERATOGENS;

EID: 84898677291     PISSN: 15429733     EISSN: 15429741     Source Type: Journal    
DOI: 10.1002/bdrb.21107     Document Type: Article

References (81)

1. Ababneh D, Ritchie H, Webster WS. 2012. Antidepressants cause bradycardia and heart block in GD 13 rat embryos in vitro. Birth Defects Res B Dev Reprod Toxicol 95(2):184-193.
2. Abela D, Ritchie H, Ababneh D, Gavin C, Nilsson MF, Khan MK, Carlsson K, Webster WS. 2010. The effect of drugs with ion channel-blocking activity on the early embryonic rat heart. Birth Defects Res B Dev Reprod Toxicol 89(5):429-440.
3. Abrahamsson C, Palmer M, Ljung B, Duker G, Baarnhielm C, Carlsson L, Danielsson B. 1994. Induction of rhythm abnormalities in the fetal rat heart. A tentative mechanism for the embryotoxic effect of the class III antiarrhythmic agent almokalant. Cardiovasc Res 28(3):337-344.
4. Andrade SE, Gurwitz JH, Davis RL, Chan KA, Finkelstein JA, Fortman K, McPhillips H, Raebel MA, Roblin D, Smith DH, Yood MU, Morse AN, Platt R. 2004. Prescription drug use in pregnancy. Am J Obstet Gynecol 191(2):398-407.
5. Andrews WW, Goldenberg RL, Mercer B, Iams J, Meis P, Moawad A, Das A, Vandorsten JP, Caritis SN, Thurnau G, Miodovnik M, Roberts J, McNellis D. 2000. The Preterm Prediction Study: association of second-trimester genitourinary chlamydia infection with subsequent spontaneous preterm birth. Am J Obstet Gynecol 183(3):662-668.
6. Attenburrow AA, Barker CM. 1985. Chlamydial pneumonia in the low birthweight neonate. Arch Dis Child 60(12):1169-1172.
7. Bekler C, Kultursay N, Ozacar T, Sayiner A, Yalaz M, Akisu M. 2012. Chlamydial infections in term and preterm neonates. Jpn J Infect Dis 65(1):1-6.
8. Blas MM, Canchihuaman FA, Alva IE, Hawes SE. 2007. Pregnancy outcomes in women infected with Chlamydia trachomatis: a population-based cohort study in Washington State. Sex Transm Infect 83(4):314-318.
9. CDC. 2010. Sexually transmitted diseases treatment guidelines, 2010. Available at: http://www.cdc.gov/std/treatment/2010/STD-Treatment-2010-RR5912.pdf. Accessed 11 December 2013.
10. Chow JM, Yonekura ML, Richwald GA, Greenland S, Sweet RL, Schachter J. 1990. The association between Chlamydia trachomatis and ectopic pregnancy. A matched-pair, case-control study. JAMA 263(23):3164-3167.
11. Clark RL, Robertson RT, Peter CP, Bland JA, Nolan TE, Oppenheimer L, Bokelman DL. 1986. Association between adverse maternal and embryo-fetal effects in norfloxacin-treated and food-deprived rabbits. Fundam Appl Toxicol 7(2):272-286.
12. Cooper WO, Hernandez-Diaz S, Arbogast PG, Dudley JA, Dyer SM, Gideon PS, Hall KS, Kaltenbach LA, Ray WA. 2009. Antibiotics potentially used in response to bioterrorism and the risk of major congenital malformations. Paediatr Perinat Epidemiol 23(1):18-28.
13. Crider KS, Cleves MA, Reefhuis J, Berry RJ, Hobbs CA, Hu DJ. 2009. Antibacterial medication use during pregnancy and risk of birth defects: National Birth Defects Prevention Study. Arch Pediatr Adolesc Med 163(11):978-985.
14. Czeizel AE, Rockenbauer M, Sorensen HT, Olsen J. 1999. A population-based case-control teratologic study of oral erythromycin treatment during pregnancy. Reprod Toxicol 13(6):531-536.
15. Danan G, Descatoire V, Pessayre D. 1981. Self-induction by erythromycin of its own transformation into a metabolite forming an inactive complex with reduced cytochrome P-450. J Pharmacol Exp Ther 218(2):509-514.
16. Danielsson BR, Skold AC, Azarbayjani F. 2001. Class III antiarrhythmics and phenytoin: teratogenicity due to embryonic cardiac dysrhythmia and reoxygenation damage. Curr Pharm Des 7(9):787-802.
17. Danielsson BR, Danielsson C, Nilsson MF. 2007. Embryonic cardiac arrhythmia and generation of reactive oxygen species: common teratogenic mechanism for IKr blocking drugs. Reprod Toxicol 24(1):42-56.
18. de Bruin ML, Pettersson M, Meyboom RH, Hoes AW, Leufkens HG. 2005. Anti-HERG activity and the risk of drug-induced arrhythmias and sudden death. Eur Heart J 26(6):590-597.
19. Drugs at FDA. 2007. Label approved on 10/25/2007 (PDF) for ZITHROMAX, NDA no. 050670. Available at: http://www.accessdata.fda.gov/drugsatfda_docs/label/2007/050670s024, 050693s010, 050730s014lbl.pdf. Accessed 11 December 2013.
20. Drugs at FDA. 2009. Label approved on 09/09/2013 (PDF) for BIAXIN, NDA no. 050662. Available at: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/050662s052lbl.pdf. Accessed 11 December 2013.
21. Drugs at FDA. 2012. Label approved on 02/02/2012 (PDF) for ERYTHROCIN, NDA no. 050609. Available at: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/050609s034lbl.pdf. Accessed 11 December 2013.
22. Drugs at FDA. 2013. Label revision 03/20/2013 (PDF) for ERYC, NDA no. 050536. Available at: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/050536s021lbl.pdf. Accessed 14 February 2014.
23. Duncan RS, Ridley JM, Dempsey CE, Leishman DJ, Leaney JL, Hancox JC, Witchel HJ. 2006. Erythromycin block of the HERG K+ channel: accessibility to F656 and Y652. Biochem Biophys Res Commun 341(2):500-506.
24. Engeland A, Bramness JG, Daltveit AK, Ronning M, Skurtveit S, Furu K. 2008. Prescription drug use among fathers and mothers before and during pregnancy. A population-based cohort study of 106, 000 pregnancies in Norway 2004-2006. Br J Clin Pharmacol 65(5):653-660.
25. Gencay M, Koskiniemi M, Ammala P, Fellman V, Narvanen A, Wahlstrom T, Vaheri A, Puolakkainen M. 2000. Chlamydia trachomatis seropositivity is associated both with stillbirth and preterm delivery. APMIS 108(9):584-588.
26. Gunnstrom M, Ababneh D, Webster WS, Oakes D, Ritchie H. 2012. Antipsychotic drugs cause bradycardia in GD 13 rat embryos in vitro. Reprod Toxicol 34(3):443-450.
27. Guo J, Zhan S, Lees-Miller JP, Teng G, Duff HJ. 2005. Exaggerated block of hERG (KCNH2) and prolongation of action potential duration by erythromycin at temperatures between 37 degrees C and 42 degrees C. Heart Rhythm 2(8):860-866.
28. Heikkinen T, Laine K, Neuvonen PJ, Ekblad U. 2000. The transplacental transfer of the macrolide antibiotics erythromycin, roxithromycin and azithromycin. BJOG 107(6):770-775.
29. Hondeghem LM, Hoffmann P. 2003. Blinded test in isolated female rabbit heart reliably identifies action potential duration prolongation and proarrhythmic drugs: importance of triangulation, reverse use dependence, and instability. J Cardiovasc Pharmacol 41(1):14-24.
30. Hondeghem LM, Carlsson L, Duker G. 2001a. Instability and triangulation of the action potential predict serious proarrhythmia, but action potential duration prolongation is antiarrhythmic. Circulation 103(15):2004-2013.
31. Hondeghem LM, Dujardin K, de Clerck F. 2001b. Phase 2 prolongation, in the absence of instability and triangulation, antagonizes class III proarrhythmia. Cardiovasc Res 50(2):345-353.
32. Justo D, Zeltser D. 2006. Torsades de pointes induced by antibiotics. Eur J Intern Med 17(4):254-259.
33. Kallen BA, Otterblad Olausson P, Danielsson BR. 2005. Is erythromycin therapy teratogenic in humans? Reprod Toxicol 20(2):209-214.
34. Kallen KBM. 2008. Maternal drug use in early pregnancy and risk of cardiovascular defects in infants - a follow-up study. Reprod Toxicol 26:64-65 (Abstract).
35. Karlsson M, Danielsson BR, Nilsson MF, Danielsson C, Webster WS. 2007. New proposals for testing drugs with IKr-blocking activity to determine their teratogenic potential. Curr Pharm Des 13(29):2979-2988.
36. Khan KM, Nilsson MF, Danielsson BR, Bengtsson E. 2008. Fully automatic heart beat rate determination in digital video recordings of rat embryos. In: Perner P, Salivetti O, editors. Advances in mass data analysis of images and signals in medicine, biotechnology, chemistry and food industry. Berlin Heidelberg: Springer-Verlag. p. 27-37.
37. Khan Niazi KM, Ibrahim MT, Nilsson MF, Sköld AC, Ling G, Nyström I. 2011. Robust signal generation and analysis of rat embryonic heart rate in vitro using laplacian eigenmaps and empirical mode decomposition. In: Real P, Diaz-Pernil D, Molian-Abril H, Berciano A, Kropatsch W, editors. Lecture notes in computer science. Berlin/Heidelberg: Springer. p. 523-530.
38. Kovacs L, Nagy E, Berbik I, Meszaros G, Deak J, Nyari T. 1998. The frequency and the role of Chlamydia trachomatis infection in premature labor. Int J Gynaecol Obstet 62(1):47-54.
39. Lin KJ, Mitchell AA, Yau WP, Louik C, Hernandez-Diaz S. 2013. Safety of macrolides during pregnancy. Am J Obstet Gynecol 208(3):e221-e228.
40. Martin DH, Koutsky L, Eschenbach DA, Daling JR, Alexander ER, Benedetti JK, Holmes KK. 1982. Prematurity and perinatal mortality in pregnancies complicated by maternal Chlamydia trachomatis infections. JAMA 247(11):1585-1588.
41. Martin RL, McDermott JS, Salmen HJ, Palmatier J, Cox BF, Gintant GA. 2004. The utility of hERG and repolarization assays in evaluating delayed cardiac repolarization: influence of multi-channel block. J Cardiovasc Pharmacol 43(3):369-379.
42. Milberg P, Eckardt L, Bruns HJ, Biertz J, Ramtin S, Reinsch N, Fleischer D, Kirchhof P, Fabritz L, Breithardt G, Haverkamp W. 2002. Divergent proarrhythmic potential of macrolide antibiotics despite similar QT prolongation: fast phase 3 repolarization prevents early afterdepolarizations and torsade de pointes. J Pharmacol Exp Ther 303(1):218-225.
43. Mitchell AA, Gilboa SM, Werler MM, Kelley KE, Louik C, Hernandez-Diaz S. 2011. Medication use during pregnancy, with particular focus on prescription drugs: 1976-2008. Am J Obstet Gynecol 205(1):e51-e58.
44. MPA. 2005. Erythromycin should be avoided in early pregnancy. [Swedish]. Available at: http://www.lakemedelsverket.se/Alla-nyheter/NYHETER-2005/Erytromycin-bor-undvikas-under-tidig-graviditet/. Accessed 11 December 2013.
45. MPA. 2006. The Swedish Medical Product Agency. Antibiotic treatment during pregnancy [Swedish]. Available at: http://www.lakemedelsverket.se/upload/halso-och-sjukvard/behandlingsrekommendationer/antibiotika_gravid%5B1%5D_bokm%C3%A4rken.pdf. Accessed 11 December 2013.
46. Ness RB, Soper DE, Richter HE, Randall H, Peipert JF, Nelson DB, Schubeck D, McNeeley SG, Trout W, Bass DC, Hutchison K, Kip K, Brunham RC. 2008. Chlamydia antibodies, chlamydia heat shock protein, and adverse sequelae after pelvic inflammatory disease: the PID Evaluation and Clinical Health (PEACH) Study. Sex Transm Dis 35(2):129-135.
47. Nilsson MF, Danielsson C, Skold AC, Johansson A, Blomgren B, Wilson J, Khan KM, Bengtsson E, Kultima K, Webster WS, Danielsson BR. 2010. Improved methodology for identifying the teratogenic potential in early drug development of hERG channel blocking drugs. Reprod Toxicol 29(2):156-163.
48. Nilsson MF, Skold AC, Ericson AC, Annas A, Villar RP, Cebers G, Hellmold H, Gustafson AL, Webster WS. 2013. Comparative effects of sodium channel blockers in short term rat whole embryo culture. Toxicol Appl Pharmacol 272(2):306-12.
49. Pacifici GM, Nottoli R. 1995. Placental transfer of drugs administered to the mother. Clin Pharmacokinet 28(3):235-269.
50. Persson K, Ronnerstam R, Svanberg L, Pohla MA. 1983. Neonatal chlamydial eye infection: an epidemiological and clinical study. Br J Ophthalmol 67(10):700-704.
51. Philipson A, Sabath LD, Charles D. 1973. Transplacental passage of erythromycin and clindamycin. N Engl J Med 288(23):1219-1221.
52. Plumb DC. 2008. Plumb's veterinary drug handbook. 6 ed. Stockholm, WI: Blackwell Publishing.
53. Ramsey PS, Vaules MB, Vasdev GM, Andrews WW, Ramin KD. 2003. Maternal and transplacental pharmacokinetics of azithromycin. Am J Obstet Gynecol 188(3):714-718.
54. Ray WA, Murray KT, Meredith S, Narasimhulu SS, Hall K, Stein CM. 2004. Oral erythromycin and the risk of sudden death from cardiac causes. N Engl J Med 351(11):1089-1096.
55. Redfern WS, Carlsson L, Davis AS, Lynch WG, MacKenzie I, Palethorpe S, Siegl PK, Strang I, Sullivan AT, Wallis R, Camm AJ, Hammond TG. 2003. Relationships between preclinical cardiac electrophysiology, clinical QT interval prolongation and torsade de pointes for a broad range of drugs: evidence for a provisional safety margin in drug development. Cardiovasc Res 58(1):32-45.
56. Robertson JN, Ward ME, Conway D, Caul EO. 1987. Chlamydial and gonococcal antibodies in sera of infertile women with tubal obstruction. J Clin Pathol 40(4):377-383.
57. Romoren M, Lindbaek M, Nordeng H. 2012. Pregnancy outcome after gestational exposure to erythromycin - a population-based register study from Norway. Br J Clin Pharmacol 74(6):1053-1062.
58. Rours IG, Hammerschlag MR, Ott A, de Faber TJ, Verbrugh HA, de Groot R, Verkooyen RP. 2008. Chlamydia trachomatis as a cause of neonatal conjunctivitis in Dutch infants. Pediatrics 121(2):e321-e326.
59. Rours GI, Duijts L, Moll HA, Arends LR, de Groot R, Jaddoe VW, Hofman A, Steegers EA, Mackenbach JP, Ott A, Willemse HF, van der Zwaan EA, Verkooijen RP, Verbrugh HA. 2011. Chlamydia trachomatis infection during pregnancy associated with preterm delivery: a population-based prospective cohort study. Eur J Epidemiol 26(6):493-502.
60. Schachter J, Grossman M, Sweet RL, Holt J, Jordan C, Bishop E. 1986. Prospective study of perinatal transmission of Chlamydia trachomatis. JAMA 255(24):3374-3377.
61. Shaffer D, Singer S, Korvick J, Honig P. 2002. Concomitant risk factors in reports of torsades de pointes associated with macrolide use: review of the United States Food and Drug Administration Adverse Event Reporting System. Clin Infect Dis 35(2):197-200.
62. Shepard TH. 1998. Human teratogens - proven, possible, and unlikely (May, 1998). Catalog of teratogenic agents. Baltimore: John Hopkins University Press. p xxiii-xxv.
63. Skold AC, Danielsson BR. 2000. Developmental toxicity of the class III antiarrhythmic agent almokalant in mice. Adverse effects mediated via induction of embryonic heart rhythm abnormalities. Arzneimittelforschung 50(6):520-525.
64. Skold AC, Danielsson BR. 2001. Developmental toxicity in the pregnant rabbit by the class III antiarrhythmic drug sotalol. Pharmacol Toxicol 88(1):34-39.
65. Skold AC, Wellfelt K, Danielsson BR. 2001. Stage-specific skeletal and visceral defects of the I(Kr)-blocker almokalant: further evidence for teratogenicity via a hypoxia-related mechanism. Teratology 64(6):292-300.
66. Skold AC, Danielsson C, Linder B, Danielsson BR. 2002. Teratogenicity of the I(Kr)-blocker cisapride: relation to embryonic cardiac arrhythmia. Reprod Toxicol 16(4):333-342.
67. Stanat SJ, Carlton CG, Crumb WJ, Jr., Agrawal KC, Clarkson CW. 2003. Characterization of the inhibitory effects of erythromycin and clarithromycin on the HERG potassium channel. Mol Cell Biochem 254(1-2):1-7.
68. Teixeira LR, Vargas FS, Acencio MM, Bumlai RU, Antonangelo L, Marchi E. 2006. Experimental pleurodesis induced by antibiotics (macrolides or quinolones). Clinics (Sao Paulo) 61(6):559-564.
69. Thompson D, Oster G. 1996. Use of terfenadine and contraindicated drugs. JAMA 275(17):1339-1341.
70. Thomsen MB, Verduyn SC, Stengl M, Beekman JD, de Pater G, van Opstal J, Volders PG, Vos MA. 2004. Increased short-term variability of repolarization predicts d-sotalol-induced torsades de pointes in dogs. Circulation 110(16):2453-2459.
71. Thomsen MB, Beekman JD, Attevelt NJ, Takahara A, Sugiyama A, Chiba K, Vos MA. 2006. No proarrhythmic properties of the antibiotics moxifloxacin or azithromycin in anaesthetized dogs with chronic-AV block. Br J Pharmacol 149(8):1039-1048.
72. van Haarst AD, van't Klooster GA, van Gerven JM, Schoemaker RC, van Oene JC, Burggraaf J, Coene MC, Cohen AF. 1998. The influence of cisapride and clarithromycin on QT intervals in healthy volunteers. Clin Pharmacol Ther 64(5):542-546.
73. Watts J, editor. 2011. Clarke's analysis of drugs and poisons in pharmaceuticals, body fluids and postmortem material. 4 ed. London, Chicago: Pharmaceutical Press.
74. Webster WS, Brown-Woodman PD, Snow MD, Danielsson BR. 1996. Teratogenic potential of almokalant, dofetilide, and d-sotalol: drugs with potassium channel blocking activity. Teratology 53(3):168-175.
75. Wellfelt K, Skold AC, Wallin A, Danielsson BR. 1999. Teratogenicity of the class III antiarrhythmic drug almokalant. Role of hypoxia and reactive oxygen species. Reprod Toxicol 13(2):93-101.
76. Westrom L, Joesoef R, Reynolds G, Hagdu A, Thompson SE. 1992. Pelvic inflammatory disease and fertility. A cohort study of 1, 844 women with laparoscopically verified disease and 657 control women with normal laparoscopic results. Sex Transm Dis 19(4):185-192.
77. Wheler CL. 2013. Antimicrobial drug use in rabbits, rodents, and ferrets. In: Giguère S, Prescott JF, Dowling PM, editors. Antimicrobial therapy in veterinary medicine. Pondicherry, India: Wiley Blackwell. p 601-622.
78. Wiesenfeld HC, Sweet RL, Ness RB, Krohn MA, Amortegui AJ, Hillier SL. 2005. Comparison of acute and subclinical pelvic inflammatory disease. Sex Transm Dis 32(7):400-405.
79. Witt A, Sommer EM, Cichna M, Postlbauer K, Widhalm A, Gregor H, Reisenberger K. 2003. Placental passage of clarithromycin surpasses other macrolide antibiotics. Am J Obstet Gynecol 188(3):816-819.
80. Volberg WA, Koci BJ, Su W, Lin J, Zhou J. 2002. Blockade of human cardiac potassium channel human ether-a-go-go-related gene (HERG) by macrolide antibiotics. J Pharmacol Exp Ther 302(1):320-327.
81. Zhou SF. 2008. Drugs behave as substrates, inhibitors and inducers of human cytochrome P450 3A4. Curr Drug Metab 9(4):310-322.