Kenji Matsuyama

Application of in Vivo Microdialysis to Transdermal Absorption of Methotrexate in Rats

Microdialysis was applied to determine the in vivo transdermal absorption of methotrexate (MTX) in rats with or without a new penetration enhancer, l-[2-(decylthio)ethyl]azacyclopentan-2-one (HPE-101). A solution composed of 2.5 mM MTX and 3% (w/v) HPE-101 was applied to the shaved abdomen, in which a semipermeable membrane cannula of 10-mm length was inserted intracutaneously with the use of an L-shaped needle. Intradermal microdialysis was performed at a flow rate of 1.0 µL/min for 12 hr. The concentration of MTX in the dialysate was measured by fluorescence polarization immunoassay (FPIA). HPE-101 (3%, w/v) significantly increased the dermal MTX concentration from 0.06±0.04 µM in the control to 56±26 µM in the dialysate from 8 to 12 hr. HPE-101 at concentrations of 0.75, 1.5, 2.25, and 3% (w/v) enhanced the total recovery of MTX in dermal dialysate from 0 to 10 hr by approximately 5, 18, 42, and 500 times compared with the control, respectively. The microdialysis system is useful for assessing in vivo transdermal drug absorption.

Evaluation of in-vivo transdermal absorption of cyclosporin with absorption enhancer using intradermal microdialysis in rats.

The purpose of this study was to evaluate the effect of absorption enhancer on in‐vivo transdermal absorption of cyclosporin using intradermal microdialysis in rats. Cyclosporin oily solutions (0.5, 2, 8% w/v) were prepared from Sandimmun (10% w/v oily oral preparation of cyclosporin) by diluting with olive oil. 1‐[2‐(Decylthio)ethyl]azacyclopentan‐2‐one (HPE‐101) and glycerin were added to the cyclosporin formulation as an absorption enhancer at various concentrations between 1 and 20%. These formulations were applied to the shaved abdomen of rats treated with intradermal microdialysis at a flow rate of 2.5 μL min−1 for 6 h.

Parameter Estimation and Dosage Adjustment in the Treatment with Vancomycin of Methicillin-Resistant Staphylococcus aureus Ocular Infections

The susceptibility of methicillin-resistant Staphylococcus aureus (MRSA) to vancomycin (VC) is excellent, but excessive dosing of VC leads to severe side effects. In this study, we present a way of administration planning for each patient based on personal data. To this end, we employed the Sawchuck-Zaske equation to calculate VC clearance (CL) and volume of distribution (Vd) on the basis of three different plasma concentrations of VC, and we used CL and Vd values as prior information before employing the parameter estimation and dosage adjustment program to treat a patient with postsurgical endophthalmitis caused by MRSA and a patient with acute dacryocystitis also caused by MRSA. They had good remissions without any severe side effects.

Development of a Pyrrolidinone Derivative (Cyclic GABA) for Modulating Brain Glutamate Transmission

Senile Dementia of Alzheimer Type (SDAT) is a debilitating neurological disease that affects about one in six persons past the age of sixty (1,2). In spite of numerous hypotheses concerning the etiology of SDAT, e.g., abnormal blood aluminum levels (3), viral agents (4), genetic factors (5) and selective vulnerability of specific neuronal systems (6,7), its precise cause or causes remain unknown.

The application of circular dichroism (CD) to a binding study of latamoxef and β-lactamase

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