Liver tissue dosing adjustments

Rat, adult 241 Am in wild molluscs or241 Am nitrate injected into mollusc tissue, twice weekly for 8 weeks 0.026-0.12 (wild mussels) 0.016-0.040 (injected mussel) Absorption estimate based on comparisons with liver and carcass 241 Am after an intravenous dose, with adjustment for excretion, twice weekly for 8 weeks Harrison et al. 1988... 

Pharmacokinetics Because of its severe toxicity to the Gl tract, 5-FU is given intravenously or, in the case of skin cancer, topically. The drug penetrates well into all tissues including the CNS. 5-FU is metabolized in the liver, largely to CO2, which is expired. The dose must be adjusted in the case of impaired hepatic function. 

Recent studies have shown that citrate can even be used in patients with significant liver disease provided that monitoring is intensified and the dose is carefully adjusted. Since the citric acid cycle is oxygen dependent, patients at greater risk of citrate accumulation seem to be those with persistent lactic acidosis due to poor tissue perfusion. Citrate is also associated with less inflammation due to hypocalcaemia-induced suppression of intracellular signalling at the cell membrane level. Whether this beneficial effect of citrate decreases mortality needs to be confirmed in clinical trials and if its safe use can be guaranteed, citrate should become the anticoagulant of choice [13 ]. 

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