
CYCLOSPORIN:
– 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
TACROLIMUS:
– 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