Renal dysfunction plasma protein

Mechanism of Action An antihyperlipidemicthat interferes with cholesterol biosynthesis by inhibiting the conversion of the enzyme hydroxymethylglutaryl-CoA (HMG-CoA) to mevalonate, a precursor to cholesterol. Therapeutic Effect Decreases LDL cholesterol, VLDL, and plasma triglyceride levels, increases HDL concentration. Pharmacokinetics Protein binding 88%. Minimal hepatic metabolism. Primarily eliminated in the feces. Half-life 19 hr (increased in patients with severe renal dysfunction). 

Severe hepatic or renal dysfunction. Reduced plasma proteins result in higher free, unbound thiopentone. 

The peak plasma concentration of oral ketorolac is reached within 30 to 60 min and may be slower after intramuscular administration. It is bound to plasma proteins by more than 99%. The terminal plasma half-life is about 4 to 6 h and is prolonged in elderly and in patients with renal dysfunction. Ketorolac is metabolized mainly by glucuronidation and to a minor extent by para-hydroxylation and is excreted in the urine ( 90%) and faeces ( 10%) (Buckley and Brogden, 1990). 

Antimetabolites cause gastrointestinal toxicity including stomatitis and diarrhoea as well as bone marrow depression renal impairment potentiates the toxicity of methotrexate. Active excreHon of methotrexate by the renal tubule is blocked by salicylate, which also displaces it from plasma protein, increasing the risk of toxicity. Hepatic dysfunction potentiates the toxicity of 5-fluorouracil, since it is primarily metabolised by the liver. 

Table 3 Altered plasma protein binding of drugs associated with renal dysfunction...

Cabre A, Lazaro 1, Girona J, Manzanares J, Marimon F, Plana N, Heras M, Masana LRetinol-binding protein 4as a plasma biomarker of renal dysfunction and cardiovascular disease in type 2 diabetes. J Intern Med. 2007 262 496-503. 

PO. 90% plasma protein bound, extensively metabolized, i dose w/renal or hepatic dysfunction. 

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