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Biomedical subjects

E Yukawa

Publications and source records attributed to E Yukawa.

68 records · Page 4Linked to original sources
PubMed1989

The effect of concurrent administration of sodium valproate on serum levels of primidone and its metabolite phenobarbital.

The effect of associated therapy on serum primidone (PRM) and derived phenobarbital (PB) concentrations, and on serum concentrations to PRM dose ratios (L/D ratio) were evaluated retrospectively from 100 consecutive PRM and derived PB determinations in 100 chronically treated epileptic patients. PRM administered was significantly (P less than 0.01) correlated with both serum PRM (r = 0.799 approximately 0.933) and derived PB levels (r = 0.545 approximately 0.870) in patients taking PRM. Derived PB L/D ratios and PB/PRM concentration ratios were higher in patients taking PRM in combination with phenytoin (PHT) and/or sodium valproate (VPA). Therefore, serum levels of PRM and derived PB should be monitored closely in patients taking PRM with PHT and/or VPA.

Adolescent↗
PubMed1989

Clinical utility of a new and simple technique for individualizing phenytoin dosage.

Wagner proposed a new and simple method to predict dosage of drugs obeying simple Michaelis-Menten elimination kinetics. From his theory the following equation, Dn = Do + 1n (Cd/Co)/S can be derived, which forms the basis of predicting the required dosage (Dn) to obtain a desired steady-state concentration (Cd), using initial steady-state concentration (Co), obtained with initial dose (Do) and a population value of S for the drug. We retrospectively investigated the value of S for phenytoin (PHT) in a population of 55 outpatients who had three or more reliable measurements of the steady-state concentration of PHT in serum, measured while they were taking different daily doses. The value of S for PHT was estimated to be 0.0122759 in Japanese patients. The predictive performance of this equation was compared with Bayesian feedback method (B) using retrospective data from 220 outpatients. This equation yielded mean error (ME) of 0.0, mean absolute error (MAE) of 30.7 and root mean squared error (RMSE) of 40.9 mg/d compared to ME of -2.5, MAE of 30.3 and RMSE of 40.1 mg/d for B method. These results indicate that this equation may be a useful adjunct for prediction of PHT dosage as well as B method. Moreover, the simplicity of the equation allows calculation on a hand-held calculator.

Adolescent↗
PubMed1989

Clinical evaluation of population pharmacokinetic parameters in phenytoin dosage adjustment.

We investigated the influence of the population pharmacokinetic parameters on the performance of the Bayesian feedback method in predicting the phenytoin (PHT) dosage needed to achieve a desired PHT serum concentration. Population pharmacokinetic parameters studied were taken from reports by Sheiner et al. (I), Grasela et al. (II), Miller et al. (III), and the authors (IV). The predictive abilities of the Bayesian feedback method were evaluated by using retrospective data from 70 patients. The mean prediction error, mean absolute prediction error (MAE), and root mean squared error (RMSE) served as measures of prediction bias and precision. The precision of the initial estimates based on the population parameter set IV was superior to those of other initial estimates studied. The performance of the Bayesian feedback method to predict PHT dosage at the steady state was relatively insensitive to bias in the estimates of the population parameters. However, the revised estimates derived from the Bayesian feedback method using the population parameter set IV with one feedback gave the lowest MAE and RMSE in predicting PHT dosage.

Adult↗
PubMed1988

Comparison of single-point phenytoin dosage prediction techniques.

To dose the anticonvulsant phenytoin (PHT) in a clinical situation is difficult because of the non-linear metabolism of the drug. Therefore many techniques have been advocated to aid dosage adjustments based on a single-point PHT concentration determined at steady-state (ss). We retrospectively investigated six methods in a population of 130 out-patients treated with PHT. The dose needed to achieve a desired PHT concentration at ss was calculated based on an observed ss dose-concentration pair using a Bayesian feedback method (B), the Richens and Dunlop nomogram (RD), the Rambeck nomogram (R), the Martin nomogram (M), a population clearance equation (PC), and the Wagner equation (W). The mean prediction error (ME), mean absolute error (MAE), and root mean squared error (RMSE) were separately calculated for each method, and served as a measure of prediction bias and precision. The MEs for B, RD, R, M, PC, and W, respectively, were -0.4, 1.2, 6.9, 3.4, -1.8, and 0.0 mg/day. The MAEs were 33.9, 38.5, 44.3, 50.4, 43.5, and 53.7 mg/day. The RMSEs were 43.7, 53.1, 65.2, 63.5, 56.0, and 68.2 mg/day. The MAE and RMSE showed lowest values for method B, followed by method RD. Therefore, we assume that method B is the most accurate in making routine PHT dosage adjustments.

Adolescent↗
PubMed1988

Evaluation of single-point phenytoin dosage prediction methods in pediatric patients.

Phenytoin (PHT) dosage adjustment in a clinical situation is difficult because of the nonlinear metabolism of the drug. Therefore, many techniques have been advocated to aid in dosage adjustments based on single-point PHT concentration determined at steady-state (SS). We retrospectively investigated seven methods in a population of 90 outpatients treated with PHT. The dose needed to achieve a desired PHT concentration at SS was calculated based on an observed SS dose-concentration pair using the Richens and Dunlop nomogram (RD), the Rambeck nomogram, the Martin nomogram, the Chiba nomogram, a population clearance method, the Wagner dosing equation and the Bayesian feedback method(B). Mean prediction error, mean absolute error (MAE), and root mean squared error (RMSE) were separately calculated for each method, and served as a measure of prediction bias and precision. The MAE and RMSE were lowest for method B (MAE = 28.7 mg/d, RMSE = 36.8 mg/d), followed by method RD (MAE = 30.3 mg/d, RMSE = 40.8 mg/d). Therefore, we recommend the use of method B to make routine PHT dosage adjustments in pediatric patients when only one dose and one concentration are available.

Adolescent↗
PubMed1977

Treatment of the intestinal tuberculosis.

Twenty-seven cases of patients with intestinal tuberculosis were reported. Seventeen cases showed good response to antituberculosis chemotherapy. The numbers and size of ulceration, pseudopolyp and deformity of intestinal tract were checked by endoscopic and X-ray studies on comparative evaluation between prechemotherapeutic and postchemotherapeutic stage. In these cases, subjective symptoms were disappeared parallel with the marked improvement on X-ray and endoscopic findings. These data suggest that with current well planned antituberculosis chemotherapy program, tuberculous colitis is controlled fairly while tuberculous enteritis in controlled inadequately. Therefore, surgical procedures are commly indicated to the treatment of tuberculous enteritis.

Adult↗
PubMedDate not supplied

CYP2C19 polymorphism effect on phenobarbitone. Pharmacokinetics in Japanese patients with epilepsy: analysis by population pharmacokinetics.

OBJECTIVE: The aim of this study was to clarify the effect of genetic polymorphisms of CYP2C19 on the pharmacokinetics of phenobarbitone (PB) using a nonlinear mixed-effects model (NONMEM) analysis in Japanese adults with epilepsy. METHODS: A total of 144 serum PB concentrations were obtained from 74 subjects treated with both PB and phenytoin but without valproic acid. All patients were classified into three groups by CYP2C19 genotyping: G1, G2 and G3 were homozygous for the wild type of CYP2C19 (*1/*1), heterozygous extensive metabolizers (EMs), (*1/*2 or *1/*3), and poor metabolizers (PMs), (*2/*2, *2/*3), respectively. All data were analyzed using NONMEM to estimate pharmacokinetic parameters of PB with respect to the CYP2C19 genotype. RESULTS: Thirty-three patients belonged to G1 (44.6%), 35 to G2 (47.3%), and 6 to G3 (8.1%). The total clearance (CL) of PB significantly decreased by 18.8% in PMs (G3) relative to EMs (G1 and G2). The CL tended to be lower in G2 than in G1. CONCLUSION: In this study, we first demonstrated the effect of the CYP2C19 polymorphism on pharmacokinetics of PB by genotyping. The contribution of other metabolic enzymes in the metabolism of PB in humans remains to be elucidated; however, it appears that the disposition of PB is mediated in part by this enzyme. The estimated population clearance values in the three genotype groups can be used to predict the PB dose required to achieve an appropriate serum concentration in an individual patient.

Adolescent↗