Satsuki Tsukiai

Possible mechanism for pharmacokinetic interaction between lidocaine and mexiletine

Our objective was to elicidate the mechanism of pharmacokinetic interaction between lidocaine and mexiletine, because an unexpected increase in plasma lidocaine concentration accompanied by severe side effects was observed when mexiletine was administered to a patient with dilated cardiomyopathy.

Pharmacokinetics Study on Phenobarbital I.V. and Rectal in Neonates.

The pharmacokinetics of phenobarbital (PB) was studied in 12 newborn infants following an acute i. v. and rectal administrations, respectively. In the 10 newborns whose gestational ages were 34 to 42 weeks and 2 infants whose ages were 6 and 13 months. The subjects were seizure or intraventricular hemorrhage or asphyxia at birth. PB pharmacokinetics was compared with single dose administration. The corresponding t1/ 2 for the i. v. dose was 103.4±65.5 hr (m±S. D.) and 138.06±100.1 hr (m±S. D.) after rectal administration. Maximum concentrations 10.25±3.4 μg/ ml (4.07-14.19 μg/ml) were reached between 5.68 and 30.13 hr after rectal administration. This variation in acute PB disposition for newborns is probably of limited clinical importance.

The Effect of Cimetidine on Renal Excretion of Chlorpropamide in Rabbits. (I).

Effects of co-administration of cimetidine (CMT) on pharmacokinetic behaviors of chlorpropamide (CPA), an oral hypoglycemic agent, after intravenous injection, were investigated in rabbits.The co-administration of CMT enhanced the plasma concentration of CPA, and reduced the amount of cumulative urinary excretion of CPA after intravenous bolus injection.Furthermore, the co-administration of CMT was found to decrease the renal clearance of CPA significantly, but to have no effect on its extrarenal clearance.These clearly indicate that the interaction of CPA with CMT is generated during renal excretion.For the purpose of elucidating the cause, effects of CMT on plasma protein binding of CPA, glomerular filtration rate (GFR), renal tubular secretion of PSP, and urinary pH were investigated.Plasma protein binding of CPA, GFR, and urinary pH were unchanged with and without CMT.But urinary excretion of PSP was decreased by co-administration of CMT.These observations suggest that the co-administration of CMT may depress the renal excretion of CPA by inhibiting the tubular secretion.