Effect of blood decrease on micafungin disposition in rats.

Micafungin (MCFG) is a novel echinocandin-class antifungal agent that extensively undergoes metabolic removal in the liver. In the present study, the influence of decreased blood volume on pharmacokinetic disposition of MCFG was examined using a rat model prepared by phlebotomy. In phlebotomized rats, hematocrit level and plasma albumin concentration were decreased by 50 and 15%, respectively.

Impact of plasma exchange on pharmacokinetic disposition of micafungin.

Change in the pharmacokinetic disposition of an antifungal agent micafungin (MCFG) by 8-hour plasma exchange (PE) with 3200 mL replacement was examined in a stem cell transplant recipient. On pharmacokinetic analysis of the time course of the serum concentrations of MCFG, it was determined that PE shortened the elimination half-life of MCFG from 16.5 hours to 6.

Change in blood tacrolimus concentration by fluctuation of renal function in a bone marrow transplant patient.

The authors report a case showing a marked change in blood tacrolimus concentration due to modification of renal function in a bone marrow transplant recipient. Blood tacrolimus concentration was well controlled after transplantation, but an approximately threefold increase in the concentration was observed on day 10 even though the dosage was unchanged. Although there were no pronounced changes in hepatic enzyme activities in serum, marked elevations of renal function test values were noted; concentrations of serum creatinine (SCr) and blood urea nitrogen (BUN) were increased by more than 300% from the original levels.

Reduced elimination clearance of micafungin in rats with cholestatic hyperbilirubinemia.

We examined whether the pharmacokinetic disposition of micafungin (MCFG), an echinocandin class antifungal agent, is altered in hyperbilirubinemia using a rat model prepared by bile duct ligation (BDL). Serum bilirubin levels were increased depending upon the duration of BDL. The elimination rate constant and total body clearance (CL(tot)) of MCFG were reduced by 24% and 16%, respectively, after BDL for 1 h, but there was no significant change in the apparent volume of distribution at steady-state.

Withdrawal symptom after discontinuation of transdermal fentanyl at a daily dose of 0.6 mg.

Neurophysiologic disorders developed in three patients after discontinuation of transdermal fentanyl (TDF) at a daily dose of 0.6 mg (2.5 mg per a patch), although direct removal of a 2.

Pharmacokinetic behavior of micafungin in rats with carbon tetrachloride-induced acute hepatic failure.

We examined the pharmacokinetic behavior of micafungin, a novel antifungal agent, in rats receiving carbon tetrachloride (CCl4) at a single dose of 2.5 ml/kg. There was no significant change in the total clearance (CL(tot)) in CCl4-treated rats, while the steady-state volume of distribution (Vd(ss)) was significantly increased by CCl4 treatment.

Decrease in oral bioavailability of ciclosporin by intravenous pulse of methylprednisolone succinate in rats.

We examined the effects of high-dose methylprednisolone on the bioavailability of orally administered ciclosporin in rats. To emulate the clinical protocol of methylprednisolone pulse therapy, methylprednisolone sodium succinate (MPS), a prodrug of methylprednisolone, was intravenously administered as repeated doses (66.3 mg kg(-1)) for 3 days.

Prooxidative activities of tea catechins in the presence of Cu2+.

The ability of various tea catechins to generate H2O2 and the hydroxyl radical in the presence of the Cu2+ ion was investigated and compared with the effect of iron ions. The presence of Cu2+ accelerated the generation of H2O2 by EGC, while EGCg with Cu2+ generated a little H2O2. The presence of iron ions inhibited the generation of H2O2 by EGC.

Urinary 6beta-hydroxycortisol/17-hydroxycorticosteroids ratio as a measure of hepatic CYP3A4 capacity after enzyme induction.

Background: The correlation between the urinary 6beta-hydroxycortisol/17-hydroxycorticosteroids (6beta-OHF/17-OHCS) ratio and the metabolic capacity of the most abundant form of hepatic cytochrome P450 (CYP3A4) after induction remains unclear.

Methods: Concentrations of 6beta-OHF and 17-OHCS in spot urine specimens obtained from 61 epileptic children receiving continuous carbamazepine therapy were measured by high-performance liquid chromatography. The relationship between the urinary 6beta-OHF/17-OHCS ratio and the serum carbamazepine concentration, corrected for dose and body weight, was examined.

Influence of intravenous methylprednisolone pulse treatment on the disposition of ciclosporin and hepatic CYP3A activity in rats.

We examined the effects of high-dose methylprednisolone (MP) on the disposition of ciclosporin (CsA) and hepatic microsomal CYP3A activity using rats. Methylprednisolone sodium succinate (MPS), a prodrug of MP, was intravenously administered as repeated doses (66.3 mg kg(-1)) for 3 days or as a single dose.

Depression of phenytoin metabolic capacity by 5-fluorouracil and doxifluridine in rats.

It has been found in clinical practice that the serum level of phenytoin, of which metabolism is mediated by hepatic CYP2C enzymes, was markedly elevated by co-administration of 5-fluorouracil (5-FU) and doxifluridine (5'-deoxy-5-fluorouridine; 5'-DFUR), a prodrug of 5-FU, but the detailed mechanisms are unclear. A study using rats was undertaken to examine the effects of 5-FU and 5'-DFUR on phenytoin metabolism in hepatic microsomes and phenytoin pharmacokinetics in-vivo. Neither 5-FU nor 5'-DFUR exhibited direct inhibitory effects on hepatic microsomal phenytoin p-hydroxylation, a major metabolic route catalysed by CYP2C in rats, as in humans.

Fluctuation in therapeutic control associated with interchange of prednisolone tablet formulations: assessment of bioequivalence by dissolution test.

A 47-year-old woman received combination therapy with prednisolone (PSL), danazol, cepharanthin, ascorbic acid, and cimetidine for the treatment of idiopathic thrombocytopenic purpura. The platelet count was well controlled for over 1 year. Then the PSL tablet formulation was altered from Tablet A to Tablet B with the same treatment regimen, but the platelet counts fell drastically thereafter.

Moricizine, an antiarrhythmic agent, as a potent inhibitor of hepatic microsomal CYP1A.

We examined the inhibitory effect of moricizine (MOR) on hepatic cytochrome P-450 (CYP) in mice. Spectrophotometric analysis revealed that MOR had a relatively high affinity for CYP molecules. MOR most potently inhibited the CYP1A1-dependent ethoxyresorufin O-deethylation and the CYP1A2-dependent methoxyresorufin O-demethylation, among the metabolic reactions mediated by CYP1A, CYP2A, CYP2B, CYP2C, CYP2D, CYP2E, and CYP3A subfamilies expressed in untreated and CYP-inducer-treated hepatic microsomes.

Pharmacokinetic analysis of theophylline to assess noncompliance in therapy.

Objective: To report a case showing patient noncompliance, supported by outcomes of pharmacokinetic analysis of theophylline as a surrogate drug.

Case Summary: A 45-year-old woman with severe hypertension was treated with a variety of oral antihypertensive drugs, but there was no improvement in her elevated blood pressure. Since we suspected that her intestinal drug absorption capacity was impaired, a theophylline absorption test was performed.

Probable metabolic interaction of doxifluridine with phenytoin.

Objective: To report the marked elevation of the serum phenytoin concentration during treatment with antineoplastic agents.

Case Summary: A 51-year-old Japanese woman, who was diagnosed with multiple brain metastatic tumors, was placed on oral phenytoin at a maintenance dose of 200 mg/d (3.8 mg/kg/d) to prevent seizures.