Differences in Cerebral Distribution between Imipramine and Paroxetine via Membrane Transporters at the Rat Blood-Brain Barrier.

Purpose: The present study aimed to elucidate the transport properties of imipramine and paroxetine, which are the antidepressants, across the blood-brain barrier (BBB) in rats.

Methods: In vivo influx and efflux transport of imipramine and paroxetine across the BBB were tested using integration plot analysis and a combination of brain efflux index and brain slice uptake studies, respectively. Conditionally immortalized rat brain capillary endothelial cells, TR-BBB13 cells, were utilized to characterize imipramine and paroxetine transport at the BBB in vitro.

Estimating pediatric doses of drugs metabolized by cytochrome P450 (CYP) isozymes, based on physiological liver development and serum protein levels.

We established a method for estimating pediatric doses of drugs metabolized by cytochrome P450 (CYP) isozymes, using the free fraction of drug in plasma (fu), serum protein level (P), liver volume (LV), and CYP activity (Vmax/Km) as indices of physiological and biochemical development in children up to 15 years old. This method allows the child/adult dose ratio (D(C)/D(A))=child/adult oral clearance ratio (CL((PO)(C))/CL((PO)(A))) of drugs mainly metabolized in the liver to be estimated by the following equation: [formula: see text]. Major metabolism of drugs was ascribed to CYP1A2 for theophylline and caffeine, and CYP1A2 and CYP2D6 for propranolol and mexiletine.

[Dose estimation for renal-excretion drugs in neonates and infants based on physiological development of renal function].

We established dose estimation formulae for renal-excretion drugs using the glomerular filtration rate (GFR), tubular secretion clearance (Sc), and unbound fraction of drug in plasma (fp) as a renal function index of physiological development in neonates and infants not more than 2 years of age. A dose ratio of (DC/DA)=clearance ratio of (CLC/CLA) congruent with(fpC.GFRC)/(fpA.