Calcineurin inhibitor pharmacokinetics

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Here are some interesting points on the pharmacokinetics of immunosuppressant drugs, taken from NephSAP in July 2010. It’s always to good to have an idea of how the body manages these drugs; this can sometimes help to predict potential side effects too.
– Oral absorption is erratic, ranging from 10-70%
– Mean bioavailability is around 30%
– Two-hour value correlates better with AUC than 12-hour trough
– Absorption can be affected by food, fat content of food and GI motility problems. Neoral is a microemulsion that was developed to try to overcome some of these issues – however, there is no proven increase in patient or graft survival
– Has a high volume of distribution (3.5-13L/Kg) and is highly tissue-bound
– Follows zero-order kinetics
– Metabolism is predominantly by the P450 CYP3A4 system; only 1% is excreted unchanged in urine
– CKD and dialysis do not affect metabolism
– To convert oral to intravenous, the conversion should be approximately one third of the daily oral dose and should not exceed 2mg/Kg/day
– Mean bioavailability is 20-25%
– It is highly protein bound, having a higher concentration in whole blood than plasma; therefore levels should preferably be monitored in whole blood
– Metabolized predominantly by CYP3A4 in the liver
– To convert oral to intravenous, the conversion should be approximately 15-20% of the daily oral dose
– Seems to cause less hypertension and less dyslipidaemia (but more diabetes) than Cyclosporin

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