Journal of Literature Pharmacy Sciences

Obez Çocuk ve Adölesanlarda Farmakokinetik Değişiklikler ve İlaç Dozuna Etkileri: Geleneksel Derleme
Pharmacokinetic Alterations and Their Effects of Drug Dosing in Obese Children and Adolescents: Traditional Review
Aslınur ALBAYRAKa, Bensu KARAHALİLb
aGazi Üniversitesi Eczacılık Fakültesi, Klinik Eczacılık ABD, Ankara, TÜRKİYE
bGazi Üniversitesi Eczacılık Fakültesi, Farmasötik Toksikoloji ABD, Ankara, TÜRKİYE
J Lit Pharm Sci. 2021;10(2):231-40
doi: 10.5336/pharmsci.2021-81639
Article Language: TR
Full Text
ÖZET
 Obezite, vücudun kabul edilebilir ölçülerin üzerinde aşırı yağlanması durumudur. Çocuklarda obezite oranları giderek artmaktadır ve XXI. yüzyılın en ciddi küresel sağlık sorunlarından biri hâline gelmiştir. Dünya Sağlık Örgütü verilerine göre 2016 yılında kız çocukların %6'sı, erkek çocukların %8'i obezdir. Türkiye'de özellikle son yıllarda yapılan çalışmalar, çocuk ve adölesanlarda obezite sıklığının %10'un üzerine çıktığını göstermektedir. Çocuklarda ve adölesanlarda obeziteye neden olan pek çok faktör rol oynamaktadır. Genetik özellikler, kültürel, çevresel ve davranışsal farklılıklar gibi faktörler, enerji alımı ile enerji harcaması arasındaki dengeyi bozarak, obezitenin meydana gelmesine sebep olmaktadır. Sadece pankreatik lipaz inhibitörü olan orlistat isimli ilaç, Amerika Birleşik Devletleri Gıda ve İlaç Dairesi tarafından 12 yaş ve üstü adölesanlarda uzun vadeli obezite yönetimi için onaylanmıştır. Obezite, ilaçların farmakokinetiğini etkileyebilecek çeşitli patofizyolojik değişikliklerle ilişkilidir. Obezitede reçete edilen ilaçların çoğu subterapötik ya da supraterapötik konsantrasyonlarla tedavide başarısızlığa ve ilaç toksisite riskine neden olmaktadır. Sunulan derlemede, hastanede yatan obez çocuk ve adölesanlara en sık reçete edilen ilaçlar için mevcut obeziteye özgü farmakokinetik ve doz bilgileri sunularak tartışılmıştır. Klinisyenlerin obez çocuk ve adölesanlarda organ/doku ilaç konsantrasyonu düşüklüğü veya ilaç toksisitesiyle ilgili potansiyel ilaç tedavisi başarısızlıklarında farkındalıklarını artırmak önemlidir. Obez çocuk ve adölesanlarda ilaç cevabının olası yan etkilerin yakından izlenmesi açısından önem taşımaktadır.

Anahtar Kelimeler: Obezite; çocuk; pediatri; farmakokinetik
ABSTRACT
 Obesity is the condition of excessive fatness of the body beyond acceptable limits. Child obesity rates are on the rise and have become one of the most serious global health problems of the 21st century. According to the data of the World Health Organization, 6% of girls and 8% of boys are obese in 2016. Studies conducted in Turkey, especially in recent years, shows that children and adolescents, the prevalence of obesity exceeds 10%. There are many factors that cause obesity in children and adolescents. Factors such as genetic features, cultural, environmental and behavioral differences cause obesity by disrupting the balance between energy intake and energy expenditure. The drug called orlistat, a pancreatic lipase inhibitor, was approved by the United States Food and Drug Administration for long-term obesity management in adolescents aged 12 years and older. Obesity is associated with various pathophysiological changes that can affect the pharmacokinetics of drugs. Most drugs prescribed for obesity cause treatment failure with sub-therapeutic or supra-therapeutic concentrations and the risk of drug toxicity. In the presented review, current obesity-specific pharmacokinetics and dosage information for the drugs most frequently prescribed to hospitalized obese children and adolescents are presented and discussed. It is important to raise the awareness of clinicians about potential drug therapy failures related to low organ/tissue drug concentration or drug toxicity in obese children and adolescents. It is important to closely monitor drug response and side effects in obese children and adolescents.

Keywords: Obesity; children; pediatrics; pharmacokinetic
REFERENCES:
  1. Kyler KE, Wagner J, Hosey-Cojocari C, Watt K, Shakhnovich V. Drug dose selection in pediatric obesity: available information for the most commonly prescribed drugs to children. Paediatr Drugs. 2019;21(5):357-69. [Crossref]  [PubMed]  [PMC] 
  2. Weiss R, Kaufman FR. Metabolic complications of childhood obesity: identifying and mitigating the risk. Diabetes Care. 2008;31 Suppl 2:S310-6. [Crossref]  [PubMed] 
  3. Choudhary AK, Donnelly LF, Racadio JM, Strife JL. Diseases associated with childhood obesity. AJR Am J Roentgenol. 2007;188(4): 1118-30. [Crossref]  [PubMed] 
  4. Balakrishnan PL. Identification of obesity and cardiovascular risk factors in childhood and adolescence. Pediatr Clin North Am. 2014;61(1):153-71. [Crossref]  [PubMed] 
  5. Biro FM, Khoury P, Morrison JA. Influence of obesity on timing of puberty. Int J Androl. 2006;29(1):272-7; discussion 286-90. [Crossref]  [PubMed] 
  6. Kloiber S, Ising M, Reppermund S, Horstmann S, Dose T, Majer M, et al. Overweight and obesity affect treatment response in major depression. Biol Psychiatry. 2007;62(4):321-6. Erratum in: Biol Psychiatry. 2007;62(4):363. [Crossref]  [PubMed] 
  7. Hamzavi Abedi Y, Perkins AM, Morales MB. Childhood obesity in pediatric patients with difficult-to-control asthma in a tertiary pediatric subspecialty clinic. Allergy Asthma Proc. 2017;38(1):63-9. [Crossref]  [PubMed] 
  8. Harskamp-van Ginkel MW, Hill KD, Becker KC, Testoni D, Cohen-Wolkowiez M, Gonzalez D, et al; Best Pharmaceuticals for Children Act-Pediatric Trials Network Administrative Core Committee. Drug dosing and pharmacokinetics in children with obesity: a systematic review. JAMA Pediatr. 2015;169(7):678-85. Erratum in: JAMA Pediatr. 2015;169(12):1179. Becker, Kristian [corrected to Becker, Kristian C]. [Crossref]  [PubMed]  [PMC] 
  9. Chambers M, Reddy SP, Olaiya MT, Dunnigan DL, Wasak D, Hoskin MA, et al. Provider preference for growth charts in tracking children with obesity. J Pediatr. 2020;219:259-62. [Crossref]  [PubMed]  [PMC] 
  10. Styne DM, Arslanian SA, Connor EL, Farooqi IS, Murad MH, Silverstein JH, et al. Pediatric obesity-assessment, treatment, and prevention: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2017;102 (3):709-57. [Crossref]  [PubMed]  [PMC] 
  11. WHO Multicentre Growth Reference Study Group. WHO Child Growth Standards based on length/height, weight and age. Acta Paediatr Suppl. 2006;450:76-85. [Crossref] 
  12. Kelly AS, Barlow SE, Rao G, Inge TH, Hayman LL, Steinberger J, et al; American Heart Association Atherosclerosis, Hypertension, and Obesity in the Young Committee of the Council on Cardiovascular Disease in the Young, Council on Nutrition, Physical Activity and Metabolism, and Council on Clinical Cardiology. Severe obesity in children and adolescents: identification, associated health risks, and treatment approaches: a scientific statement from the American Heart Association. Circulation. 2013;128(15):1689-712. [PubMed] 
  13. Cheymol G. Effects of obesity on pharmacokinetics implications for drug therapy. Clin Pharmacokinet. 2000;39(3):215-31. [Crossref]  [PubMed] 
  14. Wells JC, Fewtrell MS, Williams JE, Haroun D, Lawson MS, Cole TJ. Body composition in normal weight, overweight and obese children: matched case-control analyses of total and regional tissue masses, and body composition trends in relation to relative weight. Int J Obes (Lond). 2006;30(10):1506-13. [Crossref]  [PubMed] 
  15. Sampson M, Cohen-Wolkowiez M, Benjamin D Jr, Capparelli E, Watt K. Pharmacokinetics of Antimicrobials in Obese Children. GaBI J. 2013;2(2):76-81. [Crossref]  [PubMed]  [PMC] 
  16. Guzzaloni G, Grugni G, Minocci A, Moro D, Morabito F. Liver steatosis in juvenile obesity: correlations with lipid profile, hepatic biochemical parameters and glycemic and insulinemic responses to an oral glucose tolerance test. Int J Obes Relat Metab Disord. 2000;24(6):772-6. [Crossref]  [PubMed] 
  17. Henegar JR, Bigler SA, Henegar LK, Tyagi SC, Hall JE. Functional and structural changes in the kidney in the early stages of obesity. J Am Soc Nephrol. 2001;12(6):1211-7. [Crossref]  [PubMed] 
  18. Kendrick JG, Carr RR, Ensom MH. Pharmacokinetics and drug dosing in obese children. J Pediatr Pharmacol Ther. 2010;15(2):94-109. [Crossref]  [PubMed]  [PMC] 
  19. Lim WH, Lim EM, McDonald S. Lean body mass-adjusted Cockcroft and Gault formula improves the estimation of glomerular filtration rate in subjects with normal-range serum creatinine. Nephrology (Carlton). 2006;11(3):250-6. [Crossref]  [PubMed] 
  20. Anderson BJ, Holford NH. Understanding dosing: children are small adults, neonates are immature children. Arch Dis Child. 2013;98(9):737-44. [Crossref]  [PubMed] 
  21. Mosteller RD. Simplified calculation of body-surface area. N Engl J Med. 1987;317(17):1098. [Crossref]  [PubMed] 
  22. Phillips S, Edlbeck A, Kirby M, Goday P. Ideal body weight in children. Nutr Clin Pract. 2007;22(2):240-5. [Crossref]  [PubMed] 
  23. Ross EL, Heizer J, Mixon MA, Jorgensen J, Valdez CA, Czaja AS, et al. Development of recommendations for dosing of commonly prescribed medications in critically ill obese children. Am J Health Syst Pharm. 2015;72(7):542-56. [Crossref]  [PubMed] 
  24. Koshida R, Nakashima E, Taniguchi N, Tsuji A, Benet LZ, Ichimura F. Prediction of the distribution volumes of cefazolin and tobramycin in obese children based on physiological pharmacokinetic concepts. Pharm Res. 1989;6(6):486-91. [Crossref]  [PubMed] 
  25. Donoso F A, Ulloa V D, Contreras E D, Arriagada S D. Childhood obesity: Pharmacokinetics considerations for drugs used in the Intensive Care Unit. Arch Argent Pediatr. 2019;117(2):e121-e30. [Crossref]  [PubMed] 
  26. Smith MJ, Gonzalez D, Goldman JL, Yogev R, Sullivan JE, Reed MD, et al; Best Pharmaceuticals for Children Act-Pediatric Trials Network Steering Committee. Pharmacokinetics of clindamycin in obese and nonobese children. Antimicrob Agents Chemother. 2017;61(4):e02014-16. [Crossref]  [PubMed]  [PMC] 
  27. Choi JJ, Moffett BS, McDade EJ, Palazzi DL. Altered gentamicin serum concentrations in obese pediatric patients. Pediatr Infect Dis J. 2011;30(4):347-9. [Crossref]  [PubMed] 
  28. Le J, Capparelli EV, Wahid U, Wu YSS, Romanowski GL, Tran TM, et al. Bayesian estimation of vancomycin pharmacokinetics in obese children: matched case-control study. Clin Ther. 2015;37(6):1340-51. [Crossref] 
  29. Natale S, Bradley J, Nguyen WH, Tran T, Ny P, La K, et al. Pediatric obesity: pharmacokinetic alterations and effects on antimicrobial dosing. Pharmacotherapy. 2017;37(3):361-78. [Crossref]  [PubMed] 
  30. van Rongen A, Vaughns JD, Moorthy GS, Barrett JS, Knibbe CA, van den Anker JN. Population pharmacokinetics of midazolam and its metabolites in overweight and obese adolescents. Br J Clin Pharmacol. 2015;80(5):1185-96. [Crossref]  [PubMed]  [PMC] 
  31. Diepstraten J, Chidambaran V, Sadhasivam S, Blussé van Oud-Alblas HJ, Inge T, van Ramshorst B, et al. An integrated population pharmacokinetic meta-analysis of propofol in morbidly obese and nonobese adults, adolescents, and children. CPT Pharmacometrics Syst Pharmacol. 2013;2(9):e73. [Crossref]  [PubMed]  [PMC] 
  32. van Kralingen S, Diepstraten J, Peeters MY, Deneer VH, van Ramshorst B, Wiezer RJ, et al. Population pharmacokinetics and pharmacodynamics of propofol in morbidly obese patients. Clin Pharmacokinet. 2011;50(11): 739-50. [Crossref]  [PubMed] 
  33. Vaughns JD, Ziesenitz VC, van den Anker JN. Clinical pharmacology of frequently used intravenous drugs during bariatric surgery in adolescents. Curr Pharm Des. 2015;21(39): 5650-9. [Crossref]  [PubMed] 
  34. Vaughns JD, Ziesenitz VC, Williams EF, Mushtaq A, Bachmann R, Skopp G, et al. Use of fentanyl in adolescents with clinically severe obesity undergoing bariatric surgery: a pilot study. Paediatr Drugs. 2017;19(3):251-7. Erratum in: Paediatr Drugs. 2017;19(3):269. [Crossref]  [PubMed]  [PMC] 
  35. Hoffman S, Braunreiter C. Reduced dosing of enoxaparin for venous thromboembolism in overweight and obese adolescents: a single institution retrospective review. Res Pract Thromb Haemost. 2017;1(2):188-93. [Crossref]  [PubMed]  [PMC] 
  36. Taylor BN, Bork SJ, Kim S, Moffett BS, Yee DL. Evaluation of weight-based dosing of unfractionated heparin in obese children. J Pediatr. 2013;163(1):150-3. [Crossref]  [PubMed] 
  37. Moffett BS, Ung M, Bomgaars L. Risk factors for elevated INR values during warfarin therapy in hospitalized pediatric patients. Pediatr Blood Cancer. 2012;58(6):941-4. [Crossref]  [PubMed] 
  38. Forno E, Lescher R, Strunk R, Weiss S, Fuhlbrigge A, Celedón JC; Childhood Asthma Management Program Research Group. Decreased response to inhaled steroids in overweight and obese asthmatic children. J Allergy Clin Immunol. 2011;127(3):741-9. [PubMed]  [PMC] 
  39. McGarry ME, Castellanos E, Thakur N, Oh SS, Eng C, Davis A, et al. Obesity and bronchodilator response in black and Hispanic children and adolescents with asthma. Chest. 2015;147(6):1591-8. [Crossref]  [PubMed]  [PMC] 
  40. Hakim M, Anderson BJ, Walia H, Tumin D, Michalsky MP, Syed A, et al. Acetaminophen pharmacokinetics in severely obese adolescents and young adults. Paediatr Anaesth. 2019;29(1):20-6. [Crossref]  [PubMed] 
  41. Shakhnovich V, Brian Smith P, Guptill JT, James LP, Collier DN, Wu H, et al; Best Pharmaceuticals for Children Act-Pediatric Trials Network. A population-based pharmacokinetic model approach to pantoprazole dosing for obese children and adolescents. Paediatr Drugs. 2018;20(5):483-95. [Crossref]  [PubMed]  [PMC] 
  42. Shakhnovich V, Abdel-Rahman S, Friesen CA, Weigel J, Pearce RE, Gaedigk A, et al. Lean body weight dosing avoids excessive systemic exposure to proton pump inhibitors for children with obesity. Pediatr Obes. 2019;14(1): 10.1111/ijpo.12459. [Crossref]  [PubMed]  [PMC] 
  43. van Rongen A, van der Aa MP, Matic M, van Schaik RHN, Deneer VHM, van der Vorst MM, et al. Increased metformin clearance in overweight and obese adolescents: a pharmacokinetic substudy of a randomized controlled trial. Paediatr Drugs. 2018;20(4):365-74. [Crossref]  [PubMed]  [PMC] 
  44. Bhave G, Neilson EG. Body fluid dynamics: back to the future. J Am Soc Nephrol. 2011;22(12):2166-81. [Crossref]  [PubMed]  [PMC] 
  45. Camaione L, Elliott K, Mitchell-Van Steele A, Lomaestro B, Pai MP. Vancomycin dosing in children and young adults: back to the drawing board. Pharmacotherapy. 2013;33(12):1278-87. [Crossref]  [PubMed] 
  46. Kufel WD, Seabury RW, Mogle BT, Beccari MV, Probst LA, Steele JM. Readiness to implement vancomycin monitoring based on area under the concentration-time curve: A cross-sectional survey of a national health consortium. Am J Health Syst Pharm. 2019;76(12):889-94. [Crossref]  [PubMed] 
  47. Smit C, Wasmann RE, Goulooze SC, Wiezer MJ, van Dongen EPA, Mouton JW, et al. Population pharmacokinetics of vancomycin in obesity: Finding the optimal dose for (morbidly) obese individuals. Br J Clin Pharmacol. 2020;86(2):303-17. [Crossref]  [PubMed]  [PMC] 
  48. van Rongen A, Brill MJE, Vaughns JD, Välitalo PAJ, van Dongen EPA, van Ramshorst B, et al. Higher midazolam clearance in obese adolescents compared with morbidly obese adults. Clin Pharmacokinet. 2018;57(5):601-11. [Crossref]  [PubMed]  [PMC] 
  49. Olutoye OA, Yu X, Govindan K, Tjia IM, East DL, Spearman R, et al. The effect of obesity on the ED(95) of propofol for loss of consciousness in children and adolescents. Anesth Analg. 2012;115(1):147-53. [Crossref]  [PubMed] 
  50. Dong D, Peng X, Liu J, Qian H, Li J, Wu B. Morbid obesity alters both pharmacokinetics and pharmacodynamics of propofol: dosing recommendation for anesthesia induction. drug metab dispos. 2016;44(10):1579-83. [Crossref]  [PubMed] 
  51. Dalesio NM, Lee CKK, Hendrix CW, Kerns N, Hsu A, Clarke W, et al. Effects of obstructive sleep apnea and obesity on morphine pharmacokinetics in children. Anesth Analg. 2020;131(3):876-84. [Crossref]  [PubMed]  [PMC] 
  52. Johnson PN, Skrepnek GH, Golding CL, Owora AH, Thomas AN, Miller JL. Relationship between rate of fentanyl infusion and time to achieve sedation in nonobese and obese critically ill children. Am J Health Syst Pharm. 2017;74(15):1174-83. [Crossref]  [PubMed] 
  53. Monagle P, Chan AKC, Goldenberg NA, Ichord RN, Journeycake JM, Nowak-Göttl U, et al. Antithrombotic therapy in neonates and children: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2 Suppl):e737S-e801S. Erratum in: Chest. 2014;146(6):1694. Dosage error in article text. Erratum in: Chest. 2014;146(5):1422. [Crossref]  [PubMed]  [PMC] 
  54. Matson KL, Horton ER, Capino AC; Advocacy Committee for the Pediatric Pharmacy Advocacy Group. Medication dosage in overweight and obese children. J Pediatr Pharmacol Ther. 2017;22(1):81-3. [Crossref]  [PubMed]  [PMC] 
  55. Mushtaq A, Vaughns JD, Ziesenitz VC, Nadler EP, van den Anker JN. Use of enoxaparin in obese adolescents during bariatric surgery-a pilot study. Obes Surg. 2015;25(10):1869-74. [Crossref]  [PubMed] 
  56. Pitchon DN, Dayan AC, Schwenk ES, Baratta JL, Viscusi ER. Updates on multimodal analgesia for orthopedic surgery. Anesthesiol Clin. 2018;36(3):361-73. [Crossref]  [PubMed] 
  57. Barshop NJ, Capparelli EV, Sirlin CB, Schwimmer JB, Lavine JE. Acetaminophen pharmacokinetics in children with nonalcoholic fatty liver disease. J Pediatr Gastroenterol Nutr. 2011;52(2):198-202. [Crossref]  [PubMed]  [PMC] 
  58. Koebnick C, Getahun D, Smith N, Porter AH, Der-Sarkissian JK, Jacobsen SJ. Extreme childhood obesity is associated with increased risk for gastroesophageal reflux disease in a large population-based study. Int J Pediatr Obes. 2011;6(2-2):e257-63. [Crossref]  [PubMed] 
  59. Chen WY, Chang WL, Tsai YC, Cheng HC, Lu CC, Sheu BS. Double-dosed pantoprazole accelerates the sustained symptomatic response in overweight and obese patients with reflux esophagitis in Los Angeles grades A and B. Am J Gastroenterol. 2010;105(5):1046-52. [Crossref]  [PubMed] 

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4.7. "Turkiye Klinikleri" reserves the right to change the services and the context within the "SITE"  anytime. "Turkiye Klinikleri" may use this right without any notification and timelessly. "USER"s have to make the changes and/or corrections "Turkiye Klinikleri" required immediately. Any changes and/or corrections that are required by "Turkiye Klinikleri", may be made by "Turkiye Klinikleri" when needed. Any harm, criminal and civil liability resulted or will result from changes and/or corrections required by "Turkiye Klinikleri" and were not made on time by the "USER"s belongs completely to the users.

4.8. "Turkiye Klinikleri" may give links through the "SITE" to other websites and/or "CONTEXT"s and/or folders that are outside of their control and owned and run by third parties. These links are provided for ease of reference only and do not hold qualification for support the respective web SITE or the admin or declaration or guarantee for the information inside. "Turkiye Klinikleri" does not hold any responsibility over the web-sites connected through the links on the "SITE", folders and context, the services or products on the websites provided through these links or their context.

4.9. "Turkiye Klinikleri" may use the information provided to them by the "USERS" through the "SITE" in line with the terms of the "PRIVACY POLICY" and "USER CONTRACT". It may process the information or classify and save them on a database. "Turkiye Klinikleri" may also use the USER's or visitor's identity, address, e-mail address, phone number, IP number, which sections of the "SITE" they visited, domain type, browser type, date and time information to provide statistical evaluation and customized services.

5. PROPRIETARY RIGHTS

5.1. The information accessed through this "SITE" or provided by the users legally and all the elements (including but not limited to design, text, image, html code and other codes) of the "SITE" (all of them will be called as studies tied to "Turkiye Klinikleri"s copyrights) belongs to "Turkiye Klinikleri". Users do not have the right to resell, process, share, distribute, display or give someone permission to access or to use the "Turkiye Klinikleri" services, "Turkiye Klinikleri" information and the products under copyright protection by "Turkiye Klinikleri". Within hereby "Terms of Use" unless explicitly permitted by "Turkiye Klinikleri" nobody can reproduce, process, distribute or produce or prepare any study from those under "Turkiye Klinikleri" copyright protection.

5.2. Within hereby "Terms of Use", "Turkiye Klinikleri" reserves the rights for "Turkiye Klinikleri" services, "Turkiye Klinikleri" information, the products associated with "Turkiye Klinikleri" copyrights, "Turkiye Klinikleri" trademarks, "Turkiye Klinikleri" trade looks or its all rights for other entity and information it has through this website unless it is explicitly authorized by "Turkiye Klinikleri".

6. CHANGES IN THE TERMS OF USE

"Turkiye Klinikleri" in its sole discretion may change the hereby "Terms of Use" anytime announcing within the "SITE". The changed terms of the hereby "Terms of Use" will become valid when they are announced. Hereby "Terms of Use" cannot be changed by unilateral declarations of users.

7. FORCE MAJEURE

"Turkiye Klinikleri" is not responsible for executing late or never of this hereby "Terms of Use", privacy policy and "USER Contract" in any situation legally taken into account as force majeure. Being late or failure of performance or non-defaulting of this and similar cases like this will not be the case from the viewpoint of "Turkiye Klinikleri", and "Turkiye Klinikleri" will not have any damage liability for these situations. "Force majeure" term will be regarded as outside of the concerned party's reasonable control and any situation that "Turkiye Klinikleri" cannot prevent even though it shows due diligence. Also, force majeure situations include but not limited to natural disasters, rebellion, war, strike, communication problems, infrastructure and internet failure, power cut and bad weather conditions.

8. LAW AND AUTHORISATION TO FOLLOW

Turkish Law will be applied in practicing, interpreting the hereby "Terms of Use" and managing the emerging legal relationships within this "Terms of Use" in case of finding element of foreignness, except for the rules of Turkish conflict of laws. Ankara Courts and Enforcement Offices are entitled in any controversy happened or may happen due to hereby contract.

9. CLOSING AND AGREEMENT

Hereby "Terms of Use" come into force when announced in the "SITE" by "Turkiye Klinikleri". The users are regarded to agree to hereby contract terms by using the "SITE". "Turkiye Klinikleri" may change the contract terms and the changes will be come into force by specifying the version number and the date of change on time it is published in the "SITE".

 

30.03.2014

Privacy Policy

We recommend you to read the terms of use below before you visit our website. In case you agree these terms, following our rules will be to your favor. Please read our Terms of Use thoroughly.

www.turkiyeklinikleri.com website belongs to Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. and is designed in order to inform physicians in the field of health

www.turkiyeklinikleri.com cannot reach to user’s identity, address, service providers or other information. The users may send this information to the website through forms if they would like to. However, www.turkiyeklinikleri.com may collect your hardware and software information. The information consists of your IP address, browser type, operating system, domain name, access time, and related websites. www.turkiyeklinikleri.com cannot sell the provided user information (your name, e-mail address, home and work address, phone number) to the third parties, publish it publicly, or keep it in the website. Gathered information has a directing feature to be a source for the website’s visitor profile, reporting and promotion of the services.

www.turkiyeklinikleri.com uses the taken information:

-To enhance, improve and maintain the quality of the website

-To generate visitor’s profile and statistical data

-To determine the tendency of the visitors on using our website

-To send print publications/correspondences

-To send press releases or notifications through e-mail

-To generate a list for an event or competition

By using www.turkiyeklinikleri.com you are considered to agree that;

-Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. cannot be hold responsible for any user’s illegal and immoral behavior,

-Terms of use may change from time to time,

-It is not responsible for other websites’ contents it cannot control or the harms they may cause although it uses the connection they provided.

Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. may block the website to users in the following events:

-Information with wrong, incomplete, deceiving or immoral expressions is recorded to the website,

-Proclamation, advertisement, announcement, libelous expressions are used against natural person or legal identity,

-During various attacks to the website,

-Disruption of the website because of a virus.

Written, visual and audible materials of the website, including the code and the software are under protection by legal legislation.

Without the written consent of Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. the information on the website cannot be downloaded, changed, reproduced, copied, republished, posted or distributed.

All rights of the software and the design of the website belong to Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc.

Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. will be pleased to hear your comments about our terms of use. Please share the subjects you think may enrich our website or if there is any problem regarding our website.

info@turkiyeklinikleri.com