Abstract
Terapötik ilaç izlemi için farmakokinetik (FK) veriler ile Türkçe bir yazılım geliştirilmesi hedeflendi ve dar terapötik indeksli teofilinin iv doz ayarlaması yapılması amaçlandı.
Her grupta 2 tavşan oalcak şekilde 3 grup oluşturuldu. İlk gruptaki tavşanlara kilosuna göre hedef derişimi 15µg/mL olması için gereken doz geliştirilen programa hesaplatılarak uygulandı ve eliminasyon hız sabitini (ke) hesap edecek şekilde belli zamanlarda alınan kan örnekleri valide edilen HPLC metodu ile analizlendi. ke için çizilen eğimin r2 değerleri 0.86 ve 0.95 bulundu. Revize edilen FK bulguları ile gereken bireysel doz hesaplanarak 2.doz uygulaması yapılıp kan örnekleri alındı. Analizlenen sonuçlar ile teorik sonuçlar kıyaslandığında %sapma %5.53 ve %8.795 bulundu. 1. gruptan elde edilen FK bulguları, popülasyon FK’sı olarak alınarak diğer uygulamalarda kullanıldı.
Ikinci gruba iv çok doz bolus, üçüncü gruba ise iv hızlı-yavaş kombine infüzyon uygulaması yapıldı. Uygulamaya göre belirlenen zamanlarda alınan kan örneklerinin analizinden elde edilen sonuçlar teorik sonuçlarla kıyaslandı.
Sonuç olarak düşük derişimlerde teorik ile pratik arasında yüksek farklılık görülmek ile birlikte yüksek derişimlerde farklılanma çok azdır. Bu programı kullanarak teofilinin minimum toksik derişimine erişmeden ve minimum etkin derişiminin altına düşmeden istenilen düzeyde tutulması başarılmıştır. Daha büyük örneklemler ile sapmaların azaltılacağı düşünülmektedir.
Keywords
References
- Birkett, D. J. (1997). Pharmacokinetics made easy: therapeutic drug monitoring. Australian Prescriber, 20, 9–11.
- Dhillon, S., & Gill, K. (2006). Basic pharmacokinetics. In S. Dhillon & A. Kostrzewski (Eds.), Clinical Pharmacokinetics (1st ed., pp. 1–44). London and Chicago: Pharmaceutical Press.
- Erdman, S. M., Rodvold, K. A., & Pryka, R. D. (1991). An Updated Comparison of Drug Dosing Methods Part III: Aminoglycoside Antibiotics. Drug Disposition, 20(5), 374–388.
- Fda, & Cder. (2018). Bioanalytical Method Validation Guidance for Industry Biopharmaceutics Bioanalytical Method Validation Guidance for Industry Biopharmaceutics Contains Nonbinding Recommendations. Retrieved from http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/defau lt.htmand/ Freedman, D. B., & Marshall, W. (1993a).
- Theoretical Considerations. In D. B. Freedman & W. Marshall (Eds.), Therapeutic Drug Monitoring and Clinical Biochemistry. London: ACB Venture Publications.
- Freedman, D. B., & Marshall, W. (1993b). Individual Drugs. In D. B. Freedman & W. Marshall (Eds.), Therapeutic Drug Monitoring and Clinical Biochemistry. London: ACB Venture Publications.
- Freedman, D. B., & Marshall, W. (1993c). Analytical Aspects. In D. B. Freedman & W. Marshall (Eds.), Therapeutic Drug Monitoring and Clinical Biochemistry. London: ACB
Abstract
In this study, it was aimed to develop a Turkish software with pharmacokinetic (PK) data for therapeutic drug monitoring and IV dose adjustment of narrow therapeutic index theophylline.
The study involved three groups, each comprising two rabbits The dose required for the target concentration (15µg/mL) was calculated with the developed program according to the weight of the rabbits in the first group. Blood samples taken at certain times were analyzed by validated HPLC method to calculate the elimination rate constant (ke) after IV bolus administration. The r2 values for ke were found to be 0.86 and 0.95. The second dose calculated according to revised PK findings was administered and blood samples were taken. When the analyzed results and theoretical results were compared, the deviation was found to be 5.53% and 8.795%. The findings were taken as the population PK for other applications.
IV multiple dose bolus and IV fast-slow combined infusion were administered to the second group and the third group, respectively. The results obtained from the analysis of blood samples taken at the times determined according to the application were compared with the theoretical results.
As a result, although there is a high difference between theory and practice at low concentrations, there is very little variation at high concentrations. By using this program, it has been achieved to keep theophylline at the desired level without reaching the minimum toxic concentration and without falling below the minimum effective concentration. It is thought that deviations will be reduced with larger samples.
References
- Birkett, D. J. (1997). Pharmacokinetics made easy: therapeutic drug monitoring. Australian Prescriber, 20, 9–11.
- Dhillon, S., & Gill, K. (2006). Basic pharmacokinetics. In S. Dhillon & A. Kostrzewski (Eds.), Clinical Pharmacokinetics (1st ed., pp. 1–44). London and Chicago: Pharmaceutical Press.
- Erdman, S. M., Rodvold, K. A., & Pryka, R. D. (1991). An Updated Comparison of Drug Dosing Methods Part III: Aminoglycoside Antibiotics. Drug Disposition, 20(5), 374–388.
- Fda, & Cder. (2018). Bioanalytical Method Validation Guidance for Industry Biopharmaceutics Bioanalytical Method Validation Guidance for Industry Biopharmaceutics Contains Nonbinding Recommendations. Retrieved from http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/defau lt.htmand/ Freedman, D. B., & Marshall, W. (1993a).
- Theoretical Considerations. In D. B. Freedman & W. Marshall (Eds.), Therapeutic Drug Monitoring and Clinical Biochemistry. London: ACB Venture Publications.
- Freedman, D. B., & Marshall, W. (1993b). Individual Drugs. In D. B. Freedman & W. Marshall (Eds.), Therapeutic Drug Monitoring and Clinical Biochemistry. London: ACB Venture Publications.
- Freedman, D. B., & Marshall, W. (1993c). Analytical Aspects. In D. B. Freedman & W. Marshall (Eds.), Therapeutic Drug Monitoring and Clinical Biochemistry. London: ACB
Details
| Primary Language | English |
|---|---|
| Subjects | Clinical Pharmacy and Pharmacy Practice |
| Journal Section | Makaleler |
| Authors | |
| Early Pub Date | March 27, 2024 |
| Publication Date | March 28, 2024 |
| Published in Issue | Year 2024 Volume: 17 Issue: 1 |
