Taeyuki Ohshima

Comparative evaluation of microultrafiltration devices for determination of protein binding.

The free fraction of drugs was determined comparatively with new microultrafiltration devices, Molcut II (Catalogue No. SJGC type) (MLII) and (Catalogue No. PLGC type) (NML: a device derived by changing the membrane component of MLII), which were developed by Nihon Millipore Ltd., Tokyo, Japan. The results obtained with the device are compared with those of MPS-1 (MPS), which is commercially available from Amicon Co., Danvers, MA, U.S.A. Drugs tested are phenytoin, carbamazepine, valproic acid, the ophylline, phenobarbital, and gliclazide, In five of six drugs the free fraction by MLII shows lower values, although that by NML is in good agreement with MPS. The lower values of free fraction of drugs obtained with MLII may be caused by adsorption to the device. The adsorption increase is relatively correlated to increasing lipophilicity of drugs. The results suggest that physicochemical properties of each drug, especially hydrophobicity, should be taken into account, when a new device is used to examine protein binding of drugs. The NML, which is less expensive and is convenient because no special instrument is needed, is a reliable and satisfactory device for routine therapeutic free drug monitoring.

Simultaneous Separation and Sensitive Measurement of Free Fatty Acids in Ancient Pottery by High Performance Liquid Chromatography

Abstract A high-performance liquid chromatographic method for the analysis of the free fatty acid composition in ancient pottery with fluorescence detection was examined. Free fatty acids extracted from pottery were derivatized with 9-anthryldiazomethane and were analyzed using methanol-water as the mobile phase. Thirteen kinds of fatty acid were identified and well separated. Concentrations of individual fatty acids were estimated from an internal standard, p-butyl benzoic acid. The results correlated well with those from other quantitative analysis. These results indicate that the high-performance liquid chromatographic analysis of fatty acids is a reliable method for measuring individual fatty acids in ancient pottery.

Pharmacokinetic evaluation of (glycolato-O,O')diammine platinum(II) in lung lymph in sheep.

The pharmacokinetics of (glycolato‐O, O′)diammine platinum(II) (254‐S), especially the distribution and behavior in the lung lymph in sheep, was investigated and compared with that of cis‐diammine‐dichloroplatinum(II) (CDDP). The blood and lung lymph fluid were collected from the carotid artery and a lung lymph fistula, respectively, in conscious sheep following intravenous infusion of 100 mg/body of 254‐S and CDDP for 30 min. The concentrations of these platinum complexes were measured by using atomic absorption spectrometry. We analyzed the data using an anatomically based model including part of the lymphatic circulation. The ultrafilterable platinum of 254‐S showed much larger area under the curve (AUC) and transfer rate constants than that of CDDP, even though the mean residence times were the same. The total platinum showed the opposite pharmacokinetic behavior. In anesthetized sheep, when lung tissue samples were obtained by biopsy at the same times as those of blood and lung lymph sampling after infusion of these drugs, 254‐S distributed in lung tissue appeared to move more easily into lung lymph than CDDP, which tended to be retained in lung tissue. These differences in pharmacokinetic behavior between 254‐S and CDDP seemed to be caused by differences in their strength of protein binding, the association constants of 254‐S for plasma and lymph protein were much less than those of CDDP. From these results, 254‐S may have favorable therapeutic effects on intrathoracic malignacies such as lung cancer and lymph metastasis

Antitumour effects and pharmacokinetics of combination of vinblastine with a staurosporine derivative, NA-382, in P388/ADR-bearing mice.

The effects of a staurosporine derivative, N‐ethoxycarbonyl‐7‐oxostaurosporine (NA‐382), on the pharmacokinetics of vinblastine were evaluated, compared with those of verapamil, in multidrug‐resistant P388/ADR‐bearing mice.

Saturable function of P-glycoprotein as a drug-efflux pump in multidrug-resistant tumour cells.

P‐glycoprotein acts as an active drug‐efflux pump in multidrug‐resistant tumour cells. We studied the capacity of P‐glycoprotein to extrude drugs from the cells.

High Performance Liquid Chromatographic Retention Time of β-Blockers as an Index of Pharmacological Activities

Abstract The pharmacological activity of seven β-blockers was evaluated based on retention time on high performance liquid chromatographv with an internal surface reversed-phase silica column (Pinkcrton column). Significant relationships were found between the adjusted retention times for β-blockers and their pharmacological effects, such as affinity for the β1 heart receptors (r = -0.714) and the β2 lung receptors (r = -0.937). Thus retention time on high performance liquid chromatography may be a rapid and replicable approach to the prediction of pharmacological effects.

Investigation of Simultaneous Use of Kampo Extract Medicine in a Hospital.

To recognize the existing state of simultaneous use ( “Gappo” ) of Kampo extract medicines, we investigated the medicines from 3099 prescription preparations.The results were as follows: 1) The rate of two and three combined preparations was 10.1% and 0.8%, and combined kinds being 98 and 14, respectively. 2) Rate of non-reducing dose prescriptions among combined preparations was 19.1%. 3) The rate of combined kinds of crude drug from single to three comprised 70% among two combined preparations, and the rate of the major crude drug, Glycyrrhizae Radix, was 25.6%.

Development of a Gappo Information Database and Unification of Database System.

Simultaneous use of Kampo medicines ( “Gappo” ) has become fairly widespread through new prescription trials. Since there are little appropriate research data for simultaneous use, however it is difficult for pharmacists to check the prescription preparations. To obtain directly information on the safe use of Kampo medicine, we developed a Kampo medicine Gappo information database. The database information selected involved the overlapping of Kampo medicines compresing one of seven herbs: Glycyrrhizae radix, Rhei rhizoma, Rehmanniae radix, Ephedrae herba, Cinnamomi cortex, Aconiti tuber, or Gypsum fibrosum. The datebase with our previous three database, Kampo prescription preparation support database, Kampo medicine products information database, and a crude drug information database into a Unified Kampo Medicine Information Database System (UKMIDS).

Database of Medical and Drug Information from Manufacturer's Bulletins and its Utility.

Construction of a database system compiling the medical and drug information appearing in the manufacturers bulletins was prompted by the increasing need for pharmacists working with medical professionals to understand adequately the current status and perspective of medical services.This demand has been further supported by the fact that medical information obtained from the manufacturers bulletins has been confirmed to be very useful because of the straightforward explanations offered and the detailed, current therapeutic data presented for particular fields. The application software used for the database system is “MEGABOX-VP” (REED REX Co., Ltd.), a relational database. This system is composed of the eight files of bibliography, journal, content, object, drug information, medical technology, disease and ethical drug. Each file can be combined with any other file by window. The search for particular information is performed by combining key words or code numbers of files.