A10BK01 - Dapagliflozin |
Propably not porphyrinogenic |
PNP |
Side effects
Genital and urinary tract infections are common side effects of dapagliflozin that might potentially be porphyrinogenic.
Rationale
Dapagliflozin is not an inducer or an inhibitor of CYP enzymes and no pharmacokinetic porphyrinogenic effects are suspected.
Chemical description
Dapagliflozin is a selective and reversible inhibitor of sodium-glucose co-transporter 2 (SGLT2).
Therapeutic characteristics
Dapagliflozin is an anti-diabetic indicated in adults with type 2 diabetes mellitus to improve glycaemic control. It is administered orally.
Metabolism and pharmakokinetics
Dapagliflozin is bio transformed by UGT1A9 (present in liver and kidney) to dapagliflozin 3-O-glucuronide which is an inactive metabolite. CYP-mediated metabolism is only a minor clearance pathway but involves CYP1A1, 1A2, 2A6, 2C9, 2D6 and 3A4 (Kasichayanula 2014, SPC).
In humans < 10% is metabolized by oxidative metabolism (Maranghi 2015). About 75 % is excreted in the urine and 21 % in the feaces, as metabolites (UpToDate).
In an in vitro study dapagliflozin did not inhibit or induce human P450 enzymes (Obermeier 2010). An in vivo study found that dapagliflozin did not induce or inhibit CYP2C9 or CYP3A4 (Kasichayanula 2012).
Interaction studies indicates that dapagliflozin does not affect the metabolism of CYP 2C9 and CYP 3A4 substrates (Kasichayanula 2014).
References
- Scientific articles
- Kasichayanula S, Chang M, et al. Lack of pharmacokinetic interactions between dapagliflozin and simvastatin, valsartan, warfarin, or digoxin. Adv Ther. 2012 Feb;29(2):163-77. PMID 22271159. #3210
- Kasichayanula S, Liu X, et al. Clinical pharmacokinetics and pharmacodynamics of dapagliflozin, a selective inhibitor of sodium-glucose co-transporter type 2. Clin Pharmacokinet. 2014 Jan;53(1):17-27. PMID 24105299. #4768
- Maranghi M, Carnovale A, et al. Pharmacokinetics, pharmacodynamics and clinical efficacy of dapagliflozin for the treatment of type 2 diabetes. Expert Opin Drug Metab Toxicol. 2015 Jan;11(1):125-37 #3211
- Obermeier M, Yao M et al. In vitro characterization and pharmacokinetics ofdapagliflozin (BMS-512148), a potent sodiumglucose cotransporter type II inhibitor, in animals and humans. Drug Metab Dispos. 2010;38:405-414. #3207
- Drug reference publications
- Dapagliflozin: Drug information. Version 186.0. In: UpToDate. (Accessed: 8. December 2016). #3208
- Summary of Product Characteristics
- The electronic Medicines Compendium (emc). Summary of Product Characteristics (SPC). Forxiga. #3212
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