INTERACTION STUDIES OF GLIMEPIRIDE WITH SAMBILOTO HERBA EXTRACT AND ANDROGRAPHOLIDE, AND DIGITALIZATION OF PHARMACOKINETIC â PHARMACODYNAMIC DRUGS INTERACTION DATABASE
The prevalence of Diabetes Mellitus (DM) was predicted to reach 10,4% by 2040 with a mortality rate of 6%. The use of glimepiride, substrate CYP2C9, as oral antidiabetic is trending in Indonesia, but requires attention if used with inductors or inhibitors of CYP2C9 enzyme such as drugs or herbs....
Saved in:
| Main Author: | |
|---|---|
| Format: | Theses |
| Language: | Indonesia |
| Online Access: | https://digilib.itb.ac.id/gdl/view/52985 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| Institution: | Institut Teknologi Bandung |
| Language: | Indonesia |
| Summary: | The prevalence of Diabetes Mellitus (DM) was predicted to reach 10,4% by 2040
with a mortality rate of 6%. The use of glimepiride, substrate CYP2C9, as oral
antidiabetic is trending in Indonesia, but requires attention if used with inductors
or inhibitors of CYP2C9 enzyme such as drugs or herbs. The change in the
pharmacokinetics profile of glimepiride due to the modulation of its metabolic
processes can predict the potential interaction. Digitized information or
computerized decision support systems can be minimized the occurrence of drug
interactions. Currently, the application of drug interactions with herbs in the
Indonesian language is still limited. An application of drug interactions was
developed with database sources collected from In Vitro-In Vivo Correlation
(IVIVC) basic static model on CYP2C9 enzymes, research, and evaluation of
glimepiride or CYP2C9 substrate interactions with herbal. Based on systematic
review with search keywords in PubMed ((Herbal interaction) AND (2C9)),
((Herbs interaction) AND (2C9)) and in Google scholar "Herbal Interaction",
"Herbs Interaction", and "inhibition CYP2C9", there are seven herbs namely
sambiloto herb, mangosteen pericarp, pariah fructus, chili fructus, pomegranate,
turmeric rhizomes, and ginger rhizomes. The best performs of the basic static model
that will be used in the application was 1+Imax,u/Ki,u, R ?1.02 with the lowest
RMSE, GMFE, PPE, and NPE values, true positive (TP) 84.62%, and true negative
(TN) 85.71%. The research was conducted to evaluate the pharmacokinetics and
pharmacodynamics interaction of co-administration of glimepiride 1 mg/kg with
sambiloto herb extract 230 mg/kg on alloxan-induced diabetic rats. Glimepiride
concentration in plasma was determined by validated LC-ESI-MS/MS system with
positive ion mode m/z 491 ?126 (LOQ 2 ng/mL), whilst blood glucose levels with
GOD-PAP. The result in diabetic rats showed additive pharmacodynamics
interaction with higher AAC value 42.19% than a single administration of
glimepiride (p<0.05) with a moderate risk level. Evaluation of interaction studies
of glimepiride or other CYP2C9 substrates with chili fructus in diabetic rats and
ginger rhizomes in diabetic rats and human showed additive pharmacodynamic
interactions and antagonistic interaction alongside mangosteen pericarp in
diabetic rats but did not show pharmacokinetic interactions. Turmeric rhizome and
pomegranate showed additive pharmacodynamics interaction in diabetic rats and
human, however pharmacokinetics interaction have only been showed in diabetic
rats. The co-administration with a pariah fructus water extract shows a major risk
level which led to mortality in diabetic rats and severe hypoglycemia in human.
|
|---|