Determination of R(+)- and S(-)-lansoprazole using chiral stationary-phase liquid chromatography and their enantioselective pharmacokinetics in humans.

PURPOSE: Stereoselective and sensitive methods employing chiral stationary phase columns for HPLC determination of enantiomers of lansoprazole in the human serum were developed and pharmacokinetic behaviors of the enantiomers were evaluated in seven subjects. METHODS: Five chiral stationary phase columns: Chiralcel OD (cellulose tris(3,5-dimethyl-phenylcarbamate)), OF (cellulose tris(4-chlorophenylcarbamate)), OG (cellulose tris(4-methylphenylcarbamate)) and OJ (cellulose tris(4-methylbenzoate)), and Chiralpak AS (amylose tris ((S)-1-phenylethylcarbamate)) were investigated. RESULTS: Chiralcel OD and Chiralpak AS columns gave a good resolution of R(+)- and S(-)-enantiomers from racemic lansoprazole, but Chiralcel OF, OG, and OJ did not. The mean Cmax and the AUC values of R(+)-enantiomer were 3-5 times greater than those of S(-)-enantiomer following oral administration of 30 mg of racemic lansoprazole. The CLtot values of R(+)-enantiomer were significantly smaller than those of S(-)-enantiomer. Binding of R(+)-enantiomer to human serum proteins was significantly greater than that of S(-)-enantiomer. The mean metabolic ratio (metabolites/parent compound) in human liver microsomes of S(-)-enantiomer was significantly greater than that of R(+)-enantiomer. CONCLUSIONS: The stereoselective pharmacokinetics of lansoprazole enantiomers is likely due to its stereoselective protein binding and/or metabolism.

A new approach to chemoembolization for unresectable hepatocellular carcinoma using aclarubicin microspheres in combination with cisplatin suspended in iodized oil.

Sixty-six consecutive patients with unresectable hepatocellular carcinoma (HCC) were treated with transcatheter arterial chemoembolization (TACE) using aclarubicin microspheres (ACRms) in combination with cisplatin suspended in iodized oil (Lipiodol, Laboratoire Guerbert, Paris, France) (CSL). The stages of the disease were as follows: Stage I (n = 1), Stage II (n = 10), Stage III (n = 26), and Stage IV (n = 29). The effectiveness of TACE was assessed by comparing ACRms with CSL with ACRms without CSL. Of 66 patients treated with ACRms and CSL, 62 (93.9%) could be examined for response. According to response criteria, there were 31 (50.0%) partial responses and 17 (27.4%) minor responses. In 13 cases (21.0%) there was no change and in 1 case (1.6%) there was progressive disease. The cumulative survival rate was 80.7% at 1 year, 64.2% at 2 years, and 50.6% at 3 years. The rates were significantly higher than those of the group treated with ACRms. Eleven patients in the ACRms and CSL group experienced clinical complications: cholecystitis (4.5%), pancreatitis (3.0%), liver abscess (3.0%), hepatic failure (3.0%), gastrointestinal bleeding (1.5%), and renal failure (1.5%). No lethal side effects related to the therapy were observed. TACE using ACRms in combination with CSL prolongs the survival of patients with unresectable HCC.

Adenofibromyomatous hyperplasia of the extrahepatic bile duct--a report of two cases.

Two patients with adenofibromyomatous hyperplasia located at the distal end of the extrahepatic bile duct are reported herein. The chief symptom in both patients was upper abdominal pain and the lesions found involved the proliferation of submucosal mucous glands and fibrous elements. Further progress in imaging diagnostic techniques would increase the frequency with which such lesions are discovered. But, even now, if mural irregularities and shadow defects are found in the extrahepatic bile duct, particularly in the distal end of the common bile duct, the possibility of a benign lesion such as adenofibromyomatous hyperplasia should be taken into consideration when making a diagnosis.

Glucagon in the metabolic and nutritional management after total pancreatectomy--a case report.

The effects of exogenous glucagon on a totally pancreatectomized patient were evaluated in both the acute postoperative and convalescent periods. In the acute postoperative phase, glucagon stabilized the blood glucose level and allowed the administration of an adequate amount of energy, while during the convalescent period, it proved useful in promoting the metabolism of lipids and amino acids and maintaining liver function. Moreover, we developed a glucagon aerosol which enabled frequent administration without causing major discomfort to the patient and raised the blood glucagon to satisfactory level.

[Postoperative changes in serum levels of iron, transferrin and ferritin in surgical patients].

The association of serum levels of iron, transferrin and ferritin with surgical trauma has been analyzed in 21 surgical patients. The apparent decline of serum iron concentration was seen in the early stage of postoperative period, which was significantly manifest among the patients with major surgical process, such as pancreatectomy and hepatectomy etc. And there was no relationship between serum levels of iron and volumes of bleeding during operation and/or volumes of blood transfusion. Similarly, serum transferrin concentration decreased. On the other hand, serum ferritin concentration elevated after operation. These factors gradually returned to the preoperative levels with recovery from surgical injury. The transferrin decline in serum concentration was thought to be due to a change as rapid turnover protein. However, the decline of serum iron concentration and the elevation of serum ferritin concentration might be associated with cellular proliferative activity to repair operative injury. These results suggest that the condition of iron metabolism in management of surgical patients should be important.

[A case of intrahepatic lithiasis associated with intestinal malrotation--consideration of its etiology].

We report a case of intrahepatic lithiasis associated with intestinal malrotation, which showed some bile duct abnormalities, such as cystic dilatation accompanied with stenosis in its distal portion. The resected hepatic tissue was examined histopathologically. Cellular debris due to desquamation of the epithelium, hypersecretion of mucopolysaccharides from the proliferated intrahepatic glands, and periductal laminar or band-like fibrosis were present. The mixture of desquamated epithelium, mucopolysaccharides and bile juice occupied the bile duct lumen, suggesting intrahepatic immature gallstones. The timing of formation of the intrahepatic bile duct is nearly coincident with that of the rotation of the intestine. Intestinal malrotation is sometimes associated with the congenital biliary duct anomaly and therefore the present patient might were well be the case.