Publication: Helicobacter pylori eradikasyonunun farmakoekonomisi ve deney hayvanlarında nonstreoidal antiinflamatuvar ilaç kaynaklı ülserlerin önlenmesi
Abstract
Peptik ülser gelişiminde rolü olduğu bilinen en önemli iki faktör Helicobacter pylori varlığı ve nonsteroidal antiinflamatuvar (NSAİ) ilaç kullanımıdır. Çalışmamız, bu iki sorundan biri olan Helicobacter pylori'nin eradikasyonuna yönelik tedavi stratejilerinin farmakoekonomik yönden karşılaştırılması ve diğer önemli sorun olan NSAİ ilaçlara bağlı ülserlerin önlenmesine yönelik tedavilerin değerlendirilmesi olarak planlandı. Endoskopik olarak Helicobacter pylori (+) bulunan 75 hasta, farmakoekonomik analizi yapılacak olan 7 tedavi protokolüne rastgele atandı. 7 gün süreli, 2x30 mg Lansoprazol, 2x1 g Amoksisilin ve 2x500 mg Klaritromisin (LAK); 14 gün süreli, 2x20 mg Omeprazol, 2x250 mg Klaritromisin ve 2x500 mg Metronidazol (OKM); 1x40 mg Omeprazol, 3x500 mg Amoksisilin ve 3x500 mg Metronidazol (OAM); 3x250 mg Metronidazol, 4x500 mg Amoksisilin, 1x300 mg Ranitidin ve 4x300 mg Bizmut (MARB); 2x20 mg Omeprazol, 2x1 g Amoksisilin ve 2x500 mg Klaritromisin (OAK); 2x40 mg Omeprazol, 2x500 mg Klaritromisin ve 2x1 g Amoksisilin (OKA); 2x20 mg Omeprazol, 3x500 mg Amoksisilin ve 4x300 mg Bizmut (OAB) tedavi protokolleriyle tedavi edilen hastalar, tedavi bitiminden 2 ay sonra ikinci endoskopiyle değerlendirildiler. %90'lık eradikasyon başarısı ve 158 $'lık maliyet-etkinlik oranına ulaşan MARB, %90'lık eradikasyon başarısı ve 194 $'lık maliyet-etkinlik oranına ulaşan OKA, diğer tedavi rejimlerine göre daha maliyet-etkin bulundular. Maliyet-etkinlik oranları birbirlerine yakın bulunan LAK ve OAK arasında yapılan 'artan maliyet' analizine göre LAK'ın daha maliyet-etkin olduğu görüldü. Eradikasyon oranları sırasıyla %50, %50 ve %60 bulunan OKM, OAM ve OAB, diğer protokollere göre maliyet-etkin bulunmadılar. Deney hayvanlarında, 50 mg/ kg s.c. indometazin ile birlikte farklı dozlarda uygulanan antiülser ilaçlarının ülser oluşumunu önleme etkinlikleri değerlendirildi. 5 günlük tedavi sonunda histopatolojik olarak yapılan incelemelerde, 100 µg/ kg p.o. misoprostol (M-T1), 10 µg/ kg p.o. misoprostol (M-T2), 5 mg/ kg i.p. omeprazol (O-T1), 10 µg/ kg p.o. misoprostol + 1,5 mg/ kg omeprazol (MO-T) ve 10 µg/ kg p.o. misoprostol + 10 mg/ kg i.p. ranitidin (MR-T) tedavilerinin, indometazin kaynaklı ülserleri koruduğu görüldü. Bu tedavi rejimleriyle elde edilen koruma oranları sırasıyla, %71,4; %50; %47,6; %52,4 ve %50 bulundu. Ranitidin, bizmut ve düşük doz omeprazol ile tek tek tedavi edilen deney hayvanlarındaki ülser skorlarının, indometazin grubundan istatistiksel olarak farklı olmadığı ve sonuç olarak yeterli bir koruma sağlamadıkları görüldü. Sonuç olarak, klinik eczacıların gelecekteki en önemli rollerinden biri olarak kabul edilen farmakoekonomi alanındaki çalışmamızın, Helicobacter pylori eradikasyon tedavisine; deneysel hayvan çalışmamızın da, NSAİ ilaç kaynaklı ülserlerin önlenmesine yönelik tedavilere katkıda bulunacağına inanmaktayız.
A PHARMACOECONOMIC STUDY OF HELICOBACTER PYLORI ERADICATION AND PREVENTION OF NONSTEROIDAL ANTIINFLAMMATORY DRUG INDUCED ULCERS IN RATS 'Helicobacter pylori infection' and 'nonsteroidal antiinflammatory drug (NSAID) use' are two of the most important factors in the development of peptic ulcer disease. Our study sought to make a pharmacoeconomic comparison of different Helicobacter pylori treatment strategies and prophylactic approaches to NSAIDs induced gastrointestinal damage. A total of 75 patients diagnosed by endoscopy as Helicobacter pylori (+) were randomised to receive one of 7 Helicobacter pylori treatment protocols. These protocols were as follows: Lansoprazole 30 mg bid., Amoxicillin 1 g bid. and Clarithromycin 500 mg bid. (LAC) for 7 days; Omeprazole 20 mg bid., Clarithromycin 250 mg bid. and Metronidazole 500 mg bid. (OCM); Omeprazole 40 mg qd., Amoxicillin 500 mg tid. and Metronidazole 500 mg tid. (OAM); Metronidazole 250 mg tid., Amoxicillin 500 mg qid., Ranitidine 300 mg hs. and Bismuth 300 mg qid. (MARB); Omeprazole 20 mg bid., Amoxicillin 1 g bid. and Clarithromycin 500 mg bid. (OAC); Omeprazole 40 mg bid., Clarithromycin 500 mg bid. and Amoxicillin 1 g bid. (OCA); Omeprazole 20 mg bid., Amoxicillin 500 mg tid. and Bismuth 300 mg qid. (OAB) each for 14 days. All patients were evaluated a second time by endoscopy after 2 months of treatment. MARB and OCA were more cost-effective than the other treatment regimens. The eradication rates and cost-effectiveness ratios determined for these protocols were 90%, $158 for MARB and 90%, $194 for OCA. As we found no differences between the LAC and OAC protocols, we performed an incremental analysis of these protocols. The incremental analysis showed that LAC was more cost-effective than OAC. The OCM, OAM and OAB protocols were not found cost-effective due to their low eradication rates: 50%, 50% and 60%, respectively. We also determined the efficacy of different antiulcer drugs for the prevention of 50 mg/ kg s.c. indomethacin induced ulcer in rats. In histopathological examinations performed after 5 days of treatment, the following treatment models were found to be effective in the prevention of indomethacin induced gastric lesions: 100 µg/ kg p.o. misoprostol (M-T1), 10 µg/ kg p.o. misoprostol (M-T2), 5 mg/ kg i.p. omeprazole (O-T1), 10 µg/ kg p.o. misoprostol + 1,5 mg/ kg omeprazole (MO-T) and 10 µg/ kg p.o. misoprostol + 10 mg/ kg i.p. ranitidine (MR-T). The prevention rates achieved by these treatments were 71,4%; 50%; 47,6%; 52,4% and 50%, respectively. The ulcer scores in groups treated with ranitidine, bismuth and low dose omeprazole were not found to be different from the indomethacin group score, so that; the efficacy of these groups was not enough to prevent indomethacin induced ulcers. In conclusion, we believe that our pharmacoeconomic study will be valuable to clinicians, clinical pharmacist and all health policy makers in deciding upon appropriate Helicobacter pylori eradication treatments, while our experimental animal study will be helpful in determining NSAID induced ulcer prevention therapy.
A PHARMACOECONOMIC STUDY OF HELICOBACTER PYLORI ERADICATION AND PREVENTION OF NONSTEROIDAL ANTIINFLAMMATORY DRUG INDUCED ULCERS IN RATS 'Helicobacter pylori infection' and 'nonsteroidal antiinflammatory drug (NSAID) use' are two of the most important factors in the development of peptic ulcer disease. Our study sought to make a pharmacoeconomic comparison of different Helicobacter pylori treatment strategies and prophylactic approaches to NSAIDs induced gastrointestinal damage. A total of 75 patients diagnosed by endoscopy as Helicobacter pylori (+) were randomised to receive one of 7 Helicobacter pylori treatment protocols. These protocols were as follows: Lansoprazole 30 mg bid., Amoxicillin 1 g bid. and Clarithromycin 500 mg bid. (LAC) for 7 days; Omeprazole 20 mg bid., Clarithromycin 250 mg bid. and Metronidazole 500 mg bid. (OCM); Omeprazole 40 mg qd., Amoxicillin 500 mg tid. and Metronidazole 500 mg tid. (OAM); Metronidazole 250 mg tid., Amoxicillin 500 mg qid., Ranitidine 300 mg hs. and Bismuth 300 mg qid. (MARB); Omeprazole 20 mg bid., Amoxicillin 1 g bid. and Clarithromycin 500 mg bid. (OAC); Omeprazole 40 mg bid., Clarithromycin 500 mg bid. and Amoxicillin 1 g bid. (OCA); Omeprazole 20 mg bid., Amoxicillin 500 mg tid. and Bismuth 300 mg qid. (OAB) each for 14 days. All patients were evaluated a second time by endoscopy after 2 months of treatment. MARB and OCA were more cost-effective than the other treatment regimens. The eradication rates and cost-effectiveness ratios determined for these protocols were 90%, $158 for MARB and 90%, $194 for OCA. As we found no differences between the LAC and OAC protocols, we performed an incremental analysis of these protocols. The incremental analysis showed that LAC was more cost-effective than OAC. The OCM, OAM and OAB protocols were not found cost-effective due to their low eradication rates: 50%, 50% and 60%, respectively. We also determined the efficacy of different antiulcer drugs for the prevention of 50 mg/ kg s.c. indomethacin induced ulcer in rats. In histopathological examinations performed after 5 days of treatment, the following treatment models were found to be effective in the prevention of indomethacin induced gastric lesions: 100 µg/ kg p.o. misoprostol (M-T1), 10 µg/ kg p.o. misoprostol (M-T2), 5 mg/ kg i.p. omeprazole (O-T1), 10 µg/ kg p.o. misoprostol + 1,5 mg/ kg omeprazole (MO-T) and 10 µg/ kg p.o. misoprostol + 10 mg/ kg i.p. ranitidine (MR-T). The prevention rates achieved by these treatments were 71,4%; 50%; 47,6%; 52,4% and 50%, respectively. The ulcer scores in groups treated with ranitidine, bismuth and low dose omeprazole were not found to be different from the indomethacin group score, so that; the efficacy of these groups was not enough to prevent indomethacin induced ulcers. In conclusion, we believe that our pharmacoeconomic study will be valuable to clinicians, clinical pharmacist and all health policy makers in deciding upon appropriate Helicobacter pylori eradication treatments, while our experimental animal study will be helpful in determining NSAID induced ulcer prevention therapy.