Shigeru Katafuchi

Determination of R(+)- and S(–)-Lansoprazole Using Chiral Stationary-Phase Liquid Chromatography and Their Enantioselective Pharmacokinetics in Humans

AbstractPurpose. 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-chloro-phenylcarbamate)), 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.

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.

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 hyperpasia should be taken into consideration when making a diagnosis.

Relief of Inoperable Malignant Obstructive Jaundice following the Conversion of Percutaneous Transhepatic Bile Drainage to Internal Drainage

Patients with malignant obstructive jaundice were treated by converting percutaneous transhepatic cholangio-drainage (PTCD) to internal drainage, using a new apparatus and technique. All patients had