Teruaki Kitaura

Amnesic effects of the anticholinergic drugs, trihexyphenidyl and biperiden: differences in binding properties to the brain muscarinic receptor

An amnesic effect of anticholinergic drugs was previously described from several behavioral studies. We examined this effect induced by trihexyphenidyl and biperiden, clinically used in the parkinsonism and schizophrenic patients, by using passive avoidance tasks. Both of these drugs (0.1-10 mg/kg, s.c.) showed dose-dependent amnesic effects in the acquisition and retrieval phases. However, the effect induced by trihexyphenidyl was transient, whereas that of biperiden was long-lasting. To clarify the reason for the different duration of the amnesic activity, binding to the muscarinic receptor was examined. In the Scatchard analysis, trihexyphenidyl competed with [(3)H]quinuclidinyl benzilate ([(3)H]QNB) on the muscarinic receptor (showed increased K(d) and unchanged B(max) value), while biperiden decreased [(3)H]QNB binding (B(max) value) significantly. Furthermore, in an exchange assay for receptor inactivation, trihexyphenidyl binding to muscarinic receptors was exchanged by [(3)H]QNB completely, but biperiden decreased the exchangeable binding of [(3)H]QNB in a dose dependent manner (0.1-100 nM). These results suggested that the binding of trihexyphenidyl and biperiden to muscarinic receptor might be completely reversible and partially irreversible, respectively, whereas the K(i) values of these two drugs were similar. In conclusion, this difference in binding property may explain the difference in the time-course of the amnesic effect induced by trihexyphenidyl and biperiden.

Daily cost of ophthalmic solutions for treating glaucoma in Japan

PURPOSE We conducted a study of the daily cost of various ophthalmic solutions used in Japan for treating glaucoma: beta-adrenergic blockers (11 products), epinephrine (3), cholinergics (3), prostaglandins (2), and carbonic anhydrase inhibitors (2). METHODS The total number of drops in one bottle of each solution was counted drop by drop. The cost per drop was calculated by dividing the government-controlled standard prices by the total number of drops in one bottle. The daily cost of therapy was calculated by multiplying the cost per drop by the number of drops typically used per day. RESULTS The average cost of each preparation was calculated based on the prices and the daily usage. The daily cost of the beta-adrenergic blockers studied ranged widely, from

Increase in pepsin content in gastric mucosa during the course of aspirin-and taurocholate-induced gastric ulceration in rats

0.43 to

The Changes in the Laboratory Values During Administration of Commercially Available Ready-to-use Basal Solutions for Total Parenteral Nutrition

1.04. CONCLUSIONS These data may be useful in selecting ophthalmic products for glaucoma therapy in Japan.

Effect of Age on High-Dose Methotrexate Infusion Therapy.

To investigate the possible role of pepsin in ulceration induced by hydrogen ion backdiffusion, the ratio of alkali-labile pepsinogen to total pepsinogen was studied during the course of aspirin-and taurocholate-induced gastric ulceration in comparison with the changes in the ion permeability and histological findings. The results obtained were as follows. (1) The increase in the ucler index was observed between 1 and 2 hr with intragastric aspirin and between 2 and 4 hr with intragastric taurocholate. (2) The back-diffusion of luminal hydrogen ions, observed as a significant decrease in hydrogen ion net flux, occurred immediately in both cases with aspirin and with taurocholate. (3) A significant increase in the ratio of alkali-labile to total pepsinogen in the homogenate of gastric mucosa was observed at 30 min with aspirin and at 60 min with taurocholate. (4) Histological examination revealed the degeneration of mucosal cells spreading from the luminal surface into the mucosa, which fell off after 120 min with aspirin. These findings indicate that the activated pepsin is involved in the ulcer formation caused by the hydrogen ion back-diffusion, although the origin of the activated pepsin is not clear at the present time.

A Case Report on Patient Counseling (1). A Case Study on a Neurosurgery Patient.

Some differences are seen in the concentrations of glucose and electrolytes between commercially available ready-to-use basal solutions for total parenteral nutrition (R-TPN).In this study, we investigated the effects of the long-term administration of Unicaliq®, which contains relatively higher concentrations of chloride ions than other R-TPNs, on the clinical laboratory values. One hundred and nineteen patients, who received Unicaliq® for more than four weeks at Hiroshima University Hospital, participated in this study. The laboratory values of chloride ion (Cl-) and blood urea nitrogen (BUN) significantly increased after receiving Unicaliq® for 2 weeks, but all levels, except for BUN, returned to the pretreatment levels after 4 weeks of administration. However, these changes were slight and all were within the normal ranges.No changes were observed in other laboratory values during the 4-week administration period.These results suggest that the clinical laboratory values are not affected by the long-term administration of Unicaliq®, at least up until 4 weeks.

Study on the specificity of Shore’s method for the determination of histamine in various tissues

The effect of age on pharmacokinetics of MTX after high-dose MTX (HD-MTX) infusions was investigated. Fifty-nine patients (age: 18-83 years) received HD-MTX infusions (dosage: 1.9-3.8g/m3) for 6 hrs. All patients were divided into the following three groups according to their ages: young group (18-29 years), middle-aged group (31-57 years), and elder group (60-83 years). Mean residence time and clearance of MTX obtained by moment analysis showed a significant delay and decrease, respectively, in the elder group among patients, while there was no significance in the steady-state volume of distribution. In addition, a significantly higher concentration and slower elimination during the first 12 hr were observed in the elder group. Significant resultant decrease in renal and hepatic functions were demonstrated on days 2 and 7, respectively, indicating prompt renal damage and delayed hepatic damage in the elder patients.These results suggest that the pharmacokinetic differences among age groups were evoked by the decreased renal function at the early stage of infusions. Furthermore, drug monitoring in the early stage following the infusion is important for preventing the onset of the severe toxicity common with HD-MTX therapy in the elder patients.

Stability of Disodium Sulfobenzylpenicillin in Large Volume Parenteral Solutions

The importance of patient counseling has been recognized recently not only by pharmacists but also by other medical staffs and patients. We have started patient counseling from July 1988 on patients and developed to seven clinical departments up to the present. In practicing patient counseling, we attempt to incorporate and to put to practical use not only the drug information but also the data obtained from TDM and clinical tests. Many of the patients being seen at the Clinical Department of Neurosurgery are those who need comprehensive patient counseling involving such as drug information to continuous drug monitoring. In addition to this pharmaceutical basis, one of most important elements is that we have to know well about patients, inclusive of their physical and mental conditions, since these patients are so sensitive and nervous to change unstably.We would like to report a case of patient counseling practice using a patient of our Clinical Department of Neurosurgery as an example case cojoined with TDM and clinical data.

Pharmacokinetics of maprotiline and its demethylated metabolite in serum and specific brain regions of rats after acute and chronic administration of maprotiline

SummarySpecificity of Shore’s method for the histamine determination was investigated by examining the fluorescence spectrum of the extract from rat gastric mucosa, biopsy specimen of human gastric mucosa, human gastric juice and human whole blood. An almost identical spectrum to that of pure histamine was obtained with the extract from rat gastric mucosa and human whole blood, whereas the spectrum with the extract of human gastric biopsy specimen and human gastric juice was different from that of histamine. By means of high-performance liquid chromatography, an approximately three times more concentrated extract from human gastric mucosa gave a distinct peak of histarnine while a hundred times concentrated gastric juice gave no measurable peak of histamine.Fluorescence spectrum of the substances which might be extracted with histamine was examined. The ratio of the fluorescence of histidine to that of equimolar concentration of histamine at the wave length for histamine determination was 4.62%.From the above results, it has been concluded that Shore’s method is useful for the determination of histamine contents in the gastric mucosa and whole blood if approximately 5% contamination with histidine is taken into consideration.

Pharmacokinetic Interaction of Zonisamide in Rats. Effect of Other Antiepileptics on Zonisamide

The stability of disodium sulfobenzylpenicillin (SB-PC) in several large-volume parenteral solutions was studied. A study was also made of the influences of other additive drugs upon the stability of SB-PC in SB-PC IV fluid admixtures. Quantitative determinations were made by iodometry of the residual rate over time of SB-PC. The residual rate of SB-PC in 5-fluorouracil (5-FU injection)-10 percent glucose admixture was 67 percent after 24 hours at 25 °C, (77 °F) and in aminophylline (aminophylline injection J.P.)-10 percent glucose admixture it was 54 percent after 24 hours. It was found that the decomposition of SB-PC was due to amines which were added to these injections. In an admixture of amino acid and SB-PC, the residual rate of SB-PC decreased linearly with the increase in amino acid concentration. In the 12 kinds of amino acids used in this study, the greatest decrease was observed in the admixture with lysine, the residual rate being 76.7 percent. For the study of degradation products of SB-PC, thin layer chromatography was employed and a spot of the degradation product was detected at an Rf value of 0.2.