Kazuyo Nishihara
University of Tokyo
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Epilepsia | 1979
Kazuyo Nishihara; Katsuyoshi Uchino; Yukiya Saitoh; Yutaka Honda; Fujio Nakagawa; Zenzo Tamura
Summary: Relationships among plasma total (Ct), plasma protein unbound (Cf) and mixed salivary (Cs) concentrations of phenobarbital (PB) were studied in 29 epileptic patients. A highly significant correlation was observed between C, and Cf. Although a significant correlation was observed between Cf and Cs, Cs/Cf ratio was only 0.63. When Cs was corrected by using pKa (7.41) and pH of saliva to estimate free PB concentration (Cest f), a highly significant correlation was obtained between Cf and Cestf, and Cest f/Cf ratio was 0.96. The temporal course of Cest f obtained from Cs after an oral single dose of 50 mg PB in a healthy adult male volunteer was approximated as a triexponential equation. The peak time was 2 hr after ingestion and apparent half‐life was 66 hr. The prediction of minimum concentrations at steady state on the basis of these parameters corresponded well with actually obtained Cest f following repetitive administration of PB.
Therapeutic Drug Monitoring | 1984
Kazuyo Nishihara; Yukinao Kohda; Yukiya Saitoh; Fujio Nakagawa; Yutaka Honda
Summary A new determination method of pemoline in plasma, plasma water, mixed saliva, and urine using high-performance liquid chromatography was developed. The detection limit of pemoline using 0.2 ml of the sample was 0.02 μg/ml in plasma, plasma water, saliva, and urine. The recoveries of pemoline added to plasma, saliva, and urine (each 6 μg/ml) were more than 98%. The coefficients of variation of within-run and between-run precisions for 5 concentrations of pemoline in plasma were less than 5 and 6%, respectively. The elimination half-lives of pemoline obtained from the plasma concentration-time curves after a single oral administration of pemoline in two subjects were 6.7 and 10.3 h. Mean values of the ratio between saliva and plasma total concentration in two subjects were 0.55 and 0.64, and mean values of plasma protein binding percent were 35.7 and 25.2%, respectively. The saliva concentrations were in proportion to the plasma unbound pemoline concentrations at simultaneous samplings, and the ratios between saliva and plasma unbound concentration were about 0.9 in two subjects. Usefulness of saliva in the estimation of plasma protein-unbound pemoline concentration was noted.
Biopharmaceutics & Drug Disposition | 1999
Kazuyo Nishihara; Junko Hibino; Hajime Kotaki; Yasufumi Sawada; Tatsuji Iga
The effect of itraconazole (ITZ) on the pharmacokinetics of digoxin (DGX) was investigated in guinea pigs. The plasma concentrations of DGX in guinea pigs following treatment with ITZ (20 mg/kg intraperitoneally (ip)) after intravenous (iv) administration of DGX (0.125 mg/kg) were significantly higher than in the controls. The percentage cumulative excretion (6.9%) of DGX in bile of the ITZ‐treated group up to 6 h after administration of DGX was significantly reduced (p<0.05) compared with 10.5% in the control. The percentage cumulative excretion (3.1%) of DGX in urine of the ITZ‐treated group up to 6 h after administration was also one third that in the controls. The total, biliary, renal and metabolic clearances for DGX in the ITZ‐treated group were significantly reduced, while the Vdss was unaffected. The plasma unbound fraction of DGX (ranged 47–58%) in the ITZ‐treated group was generally similar to that in the controls (50–57%). The blood‐to‐plasma concentration ratio of DGX (range 1.28–1.42) in the absence of ITZ did not change in the presence of ITZ. Based on these results, the pharmacokinetic interaction between DGX and ITZ may be due not only to a reduction in the renal clearance but also to a reduction in the metabolic clearance of DGX by ITZ. Copyright
Annals of Pharmacotherapy | 1994
Tomofumi Santa; Kazuyo Nishihara; Shigeo Horie; Hajime Kotaki; Koujiro Yamamoto; Fuminori Shibuya; Kiyomi Ito; Yasufumi Sawada; Kazuki Kawabe; Tatsuji Iga
HAJlME KOTAKI, Ph.D. ministration of GoLytely and the blood concentration of cyclosporine returned to the therapeutic range after GoLytely lavage was stopped, we believe that the decrease resulted from poor cyclosporine absorption caused by the GoLytely lavage of the gastrointestinal tract. Proper maintenance of the blood concentration of cyclosporine is important to prevent rejection. With a gastrointestinal dysfunction such as diarrhea or treatment with a laxative such as GoLytely, the whole blood cyclosporine concentration must be monitored carefully, and intravenous administration of cyclosporine may be suitable for providing adequate immunosuppression. Decreased cycIosporine absorption after treatment with GoLytely lavage solution in a kidney transplant patient
Journal of Pharmacy and Pharmacology | 1994
Tomofumi Santa; Kazuyo Nishihara; Shigeo Horie; Hajime Kotaki; Yasufumi Sawada; Kazuki Kawabe; Tatsuji Iga
Abstract— Recently we observed a case in which the cyclosporin A absorption decreased after treatment with GoLytely lavage solution in a kidney transplant patient. In this study, we confirmed the decrease of the blood concentration of cyclosporin A after oral administration by GoLytely (Macrogol 3350) based on experiments with rats. The peak blood cyclosporin A concentration, and the area under the blood drug concentration‐time curve from 0 to 24 h in the GoLytely‐administered group were significantly lower than the control group. In the case of gastrointestinal dysfunction such as diarrhoea, or in treatment with laxatives such as GoLytely lavage solution, whole blood cyclosporin levels must be carefully monitored, and intravenous cyclosporin A may be more suitable for providing adequate immunosuppression.
Japanese Journal of Hospital Pharmacy | 1996
Yayoi Tanazawa; Hajime Kotaki; Hideki Nakagawa; Kazuyo Nishihara; Yasufumi Sawada; Tatsuji Iga
We studied retrospectively the relationship between the clinical effect of development of side effects and blood cyclosporin (CyA) concentration in patients with psoriasis, based on the blood concentration monitoring data of CyA and the clinical chart. Sixty-five percent of 50 patients received CyA within the range of 3-5 mg/kg/day dose. Although the blood concentration rose as the dose increased, intra-individual variation of the blood concentration of CyA was extremely large. The blood CyA concentration in the patients evaluated as “fully effective” was within the range of 34-297 ng/ml, and that as “insufficiently effective” was 51-375 ng/ml. Based on the evaluation of the individual patients (n=9), the clinical effects were related to the blood CyA concentration in half of the patients. Hypertension (23%) as the side effect appeared with the highest frequency, followed by the reduction of renal function (12%).We found that hypertension developed frequently more over 100 ng/ml and renal function was reduced a more over 180 ng/ml.In conclusion, It was shown that the blood CyA concentration should be monitored individually, since the optimum concentration for onset of effect was largely different among patients. Furthermore, it was demonstrated that we could advise doctors to ensurer the proper therapy through the blood CyA concentration monitoring in an attempt to avoid the onset of hypertension and renal failure which was dependent on the increasing blood CyA concentration.
Japanese Journal of Hospital Pharmacy | 1982
Kazuyo Nishihara; Yukinao Kohda; Yukiya Saitoh; Fujio Nakagawa; Zenzo Tamura
The immunoprecipitation inhibition technique (i-PiT method) was used in the clinical application to determine the concentration of carbamazepine (CBZ) and theophylline (TH) in serum. Each coefficient of variation for the 3 levels of CBZ or TH was less than 9% within-run and betweenrun. The serum CBZ concentration determined by the i-PiT method was compared with that determined by high-performance liquid chromatography (HPLC). The correlation coefficient was 0.990, but serum CBZ concentration determined by the i-PiT method was about 15% higher than that determined by HPLC because of the cross reactivity in carbamazepine-10, 11-epoxide. Other antiepileptic drugs, such as phenytoin, phenobarbital and primidone, did not interfere with the i-PiT method under therapeutic condition. The serum TH concentration determined by the i-PiT method was compared with that determined by HPLC. There was good agreement between the i-PiT method and HPLC results, where the correlation coefficient was 0.994. The metabolites of TH, such as caffeine and theobromine, did not interfere with the i-PiT method under therapeutic conditions. Therefore, the i-PiT method may be useful for the serum level monitoring of patients undergoing TH therapy.
Psychiatry and Clinical Neurosciences | 1979
Kazuyo Nishihara; Yukinao Kohda; Yukiya Saitoh; Yutaka Honda
Interaction between phenytoin (PHT) and phenobarbital( PB) in epileptic patients was studied by simultaneously determining their plasma concentrations. The subjects of study were 158 adult epileptic outpatients at the Department of Neuropsychiatry, Tokyo University Hospital, and at Fujisawa Hospital. Most of the patients suffered bilateral generalized convulsions, and were maintained at steady state concentrations of PHT and/or PB. Patients consisted of PHT group (51 patients with PHT only), PB group (6 patients with PB only) and PHT + PB group (101 patients). Plasma PHT and PB concentrations were determined by the UV method.* In both PHT and PHT + PB groups the dose-level relationships of PHT showed Michaelis-Menten type curves. In the PHT + PB group the dose-level relationship of PHT was not different from that of the PHT group when plasma PB concentrations were less than 20pg/ml. When PB concentrations were higher than 20 pg/ml, and when the PHT doses were higher than about 4.5mglkg per day, the PHT concentrations of the PHT + PB group showed a decrease when compared to the PHT group. This finding suggests that PB either accelerates the metabolism of PHT in the liver or inhibits the absorption of PHT
Journal of Pharmaceutical Sciences | 2003
Hisashi Iizasa; Naomi Genda; Tomohide Kitano; Mikio Tomita; Kazuyo Nishihara; Masahiro Hayashi; Kayako Nakamura; Shizuko Kobayashi; Emi Nakashima
Chemical & Pharmaceutical Bulletin | 1970
Tokuji Suzuki; Yukiya Saitoh; Kazuyo Nishihara