Preclinical pharmacokinetics, pharmacology and toxicology of lisdexamfetamine: a novel d-amphetamine pro-drug.

Lisdexamfetamine dimesylate (LDX) is a novel pro-drug of d-amphetamine that is currently used for the treatment of attention-deficit/hyperactivity disorder in children aged ≥ 6 years and adults. LDX is enzymatically cleaved to form d-amphetamine following contact with red blood cells, which reduces the rate of appearance and magnitude of d-amphetamine concentration in the blood and hence the brain when compared with immediate-release d-amphetamine at equimolar doses. Thus, the increase of striatal dopamine efflux and subsequent increase of locomotor activity following d-amphetamine is less prominent and slower to attain maximal effect following an equimolar dose of LDX.

Long-term treatment with lanthanum carbonate reduces mineral and bone abnormalities in rats with chronic renal failure.

Background: Lanthanum carbonate (FOSRENOL(®), Shire Pharmaceuticals) is an effective non-calcium, non-resin phosphate binder for the treatment of hyperphosphataemia in patients with chronic kidney disease (CKD). In this study, we used a rat model of chronic renal failure (CRF) to examine the long-term effects of controlling serum phosphorus with lanthanum carbonate treatment on the biochemical and bone abnormalities associated with CKD-mineral and bone disorder (CKD-MBD).

Methods: Rats were fed a normal diet (normal renal function, NRF), or a diet containing 0.

Dietary administration in rodent studies distorts the tissue deposition profile of lanthanum carbonate; brain deposition is a contamination artefact?

Lanthanum carbonate is a non-calcium phosphate binder used to control hyperphosphataemia in patients with chronic kidney disease who are undergoing dialysis. Ultrastructurally, lanthanum ions are too large to traverse the tight junctions in the blood-brain barrier, yet tissue distribution studies using dietary administration have reported low concentrations in rodent brain, raising concern about accumulation. To investigate this, tissue lanthanum concentrations were measured in rats given the same lanthanum carbonate dose via powdered diet or oral gavage (838 and 863 mg/kg/day).