Esomeprazole is 97% protien bound...my patient is havingg severe hepatic impairment due to which albumin which is protein could not be sybthesized by liver...so there will be no albumin in blood and drug amount in blood will be free due to which drug accumulates in body.so what will be consequences of increased half life of esomeprazole
If your patient s having severe hepatic impairment the albumin in blood will be lower than normal, hence the binding of the drug will be low. There will e a lot of free drug in the body, hence toxicity of the drug will be higher. The manufacturer of the drug states
Esomeprazole is extensively metabolized in the liver by the cytochrome P450 (CYP) enzyme system. The metabolites of esomeprazole lack antisecretory activity. The major part of esomeprazole's metabolism is dependent upon the CYP 2C19 isoenzyme, which forms the hydroxy and desmethyl metabolites. The remaining amount is dependent on CYP 3A4 which forms the sulphone metabolite. CYP 2C19 isoenzyme exhibits polymorphism in the metabolism of esomeprazole, since some 3% of Caucasians and 15 to 20% of Asians lack CYP 2C19 and are termed Poor Metabolizers. At steady state, the ratio of AUC in Poor Metabolizers to AUC in the rest of the population (Extensive Metabolizers) is approximately 2.
After studies on patients with hepatic insufficiency, the manufacturer recommends as follows:
In patients with severe hepatic insufficiency the AUCs were 2 to 3 times higher than in the patients with normal liver function. No dosage adjustment is recommended for patients with mild to moderate hepatic insufficiency (Child Pugh Classes A and B). However, in patients with severe hepatic insufficiency (Child Pugh Class C) a dose of 20 mg once daily should not be exceeded.
I hope this helps you.
All the best