Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:1.6.5.4 (
SOR
)
720
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Sulfonylureas, metformin, thiazolidinediones, and non-sulfonylurea secretagogues differ little in their ability to decrease glycosylated hemoglobin (Hb A1c) levels when used as initial monotherapy for diabetes mellitus type 2 (strength of recommendation [
SOR
]: A, based on systematic reviews); alpha-glucosidase inhibitors may also be as effective (
SOR
: B, based on systematic reviews with inconsistent results).
Metformin
is generally indicated in obese patients because it improves all-cause mortality and diabetes related outcomes (
SOR
: B, based on a single high-quality randomized controlled trial [RCT]). Insulin is generally not recommended as an initial agent (
SOR
: C, expert opinion).
...
PMID:Clinical inquiries. What is the best medical therapy for new-onset type 2 diabetes? 1709 Mar 63
The tyrosine kinase inhibitor sorafenib is the first-line treatment for patients with hepatocellular carcinoma (HCC), in which hyperlipidemia and type 2 diabetes mellitus (T2DM) may often coexist. Protein transporters like organic cation (OCT) and multidrug and toxin extrusion (MATE) are involved in the response to sorafenib, as well as in that to the anti-diabetic drug metformin or atorvastatin, used in hyperlipidemia. Changes in the activity of these transporters may lead to pharmacokinetic interactions, which are of clinical significance. The study aimed to assess the sorafenib-metformin and sorafenib-atorvastatin interactions in rats. The rats were divided into five groups (eight animals in each) that received sorafenib and atorvastatin (I
SOR+AT
), sorafenib and metformin (II
SOR+MET
), sorafenib (III
SOR
), atorvastatin (IV
AT
), and metformin (V
MET
). Atorvastatin significantly increased the maximum plasma concentration (C
max
) and the area under the plasma concentration-time curve (AUC) of sorafenib by 134.4% (
p
< 0.0001) and 66.6% (
p
< 0.0001), respectively. Sorafenib, in turn, caused a significant increase in the AUC of atorvastatin by 94.0% (
p
= 0.0038) and its metabolites 2-hydroxy atorvastatin (
p
= 0.0239) and 4-hydroxy atorvastatin (
p
= 0.0002) by 55.3% and 209.4%, respectively.
Metformin
significantly decreased the AUC of sorafenib (
p
= 0.0065). The AUC ratio (II
SOR+MET
group/III
SOR
group) for sorafenib was equal to 0.6. Sorafenib did not statistically significantly influence the exposure to metformin. The pharmacokinetic interactions observed in this study may be of clinical relevance in HCC patients with coexistent hyperlipidemia or T2DM.
...
PMID:Pharmacokinetic Interaction between Sorafenib and Atorvastatin, and Sorafenib and Metformin in Rats. 3260 4
