Volume : 09, Issue : 10, October – 2022



Authors :

TVijayabhargava K.* P. Rajeswarao Rao and Rajendra Prasad Y

Abstract :

As similar to metabolic pathways or metabolism of drug is inhibited competitively or by other pathways, the inhibition can be happening at the drug transport level which is also critical alongside other disposition pathways. Advances in the understanding of drug metabolic pathways and drug transport process help in the estimation of degree of invivo interaction in vitro through certain parameters like the [I]/Ki ratio. Such equations employ a blend of in vivo and in vitro derived parameters to estimate the fold change in the AUC ratio in the presence and absence of inhibitor. In the current investigation, the change in the AUC was predicted when two most commonly used drugs (Rosuvastatin and Glimepiride) were used to manage anti hyperlipidemia and diabetes. Current investigation employed the hepatic inlet concentration (determined majorly by the presence of OATP drug transporters) of Rosuvastatin which is the major rate limiting step in determining the active concentration reaching the site to elicit its therapeutic response. Alternately Glimepiride disposition is also effected by OATP transporters although at a higher affinity as shown in certain studies reported in the literature.
The results indicate a change in the rosuvastatin AUC upon long term usage of Glimepiride. However, such study need to be validated in the clinical scenario as elevated concentrations in the clinic for Rosuvastatin would precipitate the devastating Rhabdomylosis in patients who are on co-medication with the drugs under current investigation.
Keywords: Rosuvastatin, Glimepiride, Hepatic inlet concentration, OATP transporters, Cmax

Cite This Article:

Please cite this article Vijayabhargava.K et al, Prediction Of Drug-Drug Interaction Potential Of Sulfonyl Ureas On The Disposition Of Anti-Hyperlipidemia Drugs-Mathematical Modeling Approach., Indo Am. J. P. Sci, 2022; 09(10).


1. Borga O, Borga B. Serum protein binding of nonsteroidal anti-inflammatory drugs: a comparative study. Journal of Pharmacokinetics and Bio pharmaceutics. 1997; 25(1):63-77
2. Food, Drugs and Administration. In Vitro Drug Interaction Studies — Cytochrome P450 Enzyme- and Transporter-Mediated Drug Interactions Guidance for Industry. Jan 2020.
3. Egan A, Colman E. Weighing the benefits of High-Dose Simvastatin against the risk of Myopathy. New England Journal of Medicine 2011; 365(4):285-287.
4. Elsby R, Hilgendorf C, Fenner K. Understanding the critical disposition pathways of statins to assess drug-drug interaction risk during drug development: it’s not just about OATP1B1. Clin Pharmacol Ther. 2012; 92(5):584-598.
5. Haupt LJ, Kazmi F, Ogilvie BW, Buckley DB, Smith BD, Leatherman S, Paris B, Parkinson O, Parkinson A.. The Reliability of Estimating Ki Values for Direct, Reversible Inhibition of Cytochrome P450 Enzymes from Corresponding IC50 Values: A Retrospective Analysis of 343 Experiments. Drug Metab Dispos. 2015; 43(11):1744‐1750.
6. Ito K, Chiba K, Horikawa M, Ishigami M, Mizuno N, Aoki J, Gotoh Y, Iwatsubo T, Kanamitsu S, Kato M, Kawahara I, Niinuma K, Nishino A, Sato N, Tsukamoto Y, Ueda K, Itoh T, Sugiyama Y. Which concentration of the inhibitor should be used to predict in vivo drug interactions from in vitro data? AAPS PharmSci. 2002; 4(4):E25.
7. Matsushima H, Kamimura H, Soeishi Y, Watanabe T, Higuchi S, Miyazaki M. Plasma protein binding of tamsulosin hydrochloride in renal disease: role of alpha1-acid glycoprotein and possibility of binding interactions. Eur J ClinPharmacol. 1999; 55(6):437‐443.
8. Shugarts S, Benet LZ. The role of transporters in the pharmacokinetics of orally administered drugs.Pharm Res. 2009; 26(9):2039‐2054
9. Shitara Y, Sato H, Sugiyama Y. Evaluation of Drug-Drug Interaction in the Hepatobiliary and Renal transport of drugs. Annual Review of Pharmacology and Toxicology 2005 45:1, 689-723.
10. Shitara Y, Sugiyama Y. Preincubation-dependent and long-lasting inhibition of organic anion transporting polypeptide (OATP) and its impact on drug-drug interactions. Pharmacol Ther. 2017; 177:67‐80
11. Shitara Y, Sugiyama Y. Preincubation-dependent and long-lasting inhibition of organic anion transporting polypeptide (OATP) and its impact on drug-drug interactions. Pharmacol Ther. 2017; 177:67‐80.
12. Product monograph: https://products.sanofi.ca/en/amaryl.pdf. 2009, 2016.[Accessed on 11 November 2021].
13. Van de Steeg E, Greupink R, Schreurs M, Nooijen IH, Verhoeckx KC, Hanemaaijer R, Ripken D, Monshouwer M, Vlaming ML, DeGroot J, Verwei M, Russel FG, Huisman MT, Wortelboer HM. Drug-drug interactions between rosuvastatin and oral antidiabetic drugs occurring at the level of OATP1B1. Drug Metab Dispos. 2013; 41(3):592‐601.
14. Williamson B, Soars AC, Owen A, White P, Riley RJ, Soars MG. Dissecting the relative contribution of OATP1B1-mediated uptake of xenobiotics into human hepatocytes using siRNA. Xenobiotica 2013; 43:920–31.