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A Yokono

Publications and source records attributed to A Yokono.

15 recordsLinked to original sources
PubMed2001

The effect of CYP2C19 and CYP2D6 genotypes on the metabolism of clomipramine in Japanese psychiatric patients.

In this study, the authors investigated the relationship between the metabolism of clomipramine (C) and the genotypes of cytochrome P450 (CYP) CYP2C19 and CYP2D6. Fifty-one Japanese patients (18 men and 33 women) were administered 10 to 250 mg/day of C by mouth and maintained on the same daily dose of C for at least 2 weeks to obtain steady-state concentrations. Plasma levels of C and its metabolites N-desmethylclomipramine (DC), 8-hydroxyclomipramine, and 8-hydroxy-N-desmethylclomipramine (HDC) were determined by high-performance liquid chromatography. The allele frequencies of CYP2C19*2, CYP2C19*3, CYP2D6*5, and CYP2D6*10 were 27.5%, 12.8%, 2.9%, and 43.1%, respectively. Subjects who were homozygous for mutated alleles of CYP2C19 showed approximately 75% higher concentrations of C corrected by dose and body weight compared with those who were homozygous for wild-type alleles. Also, subjects who were homozygous for mutated alleles of CYP2C19 showed an approximately 68% higher value of C/DC compared with those who were homozygous for wild-type alleles. No significant difference in the ratio of DC/HDC was observed between subjects who were homozygous for mutated alleles of CYP2D6 and those who were homozygous for wild-type alleles. These results suggest that genotyping CYP2C19 is useful for grossly predicting the risk of getting high plasma concentrations of C and the low individual capacity to demethylate C because there is marked interindividual variability within each genotype. However, the genotyping of CYP2D6 is not useful for predicting the individual capacity to hydroxylate DC.

Adolescent↗
PubMed2001

Importance of the cytochrome P450 2D6 genotype for the drug metabolic interaction between chlorpromazine and haloperidol.

The authors studied the interactive effects of the coadministration of haloperidol and chlorpromazine on plasma concentrations of haloperidol and reduced haloperidol. The subjects were 43 Japanese male schizophrenic inpatients who were concomitantly treated with chlorpromazine before or after monotherapy with haloperidol. Coadministration of chlorpromazine produced significant increases in the plasma concentrations of haloperidol (P < 0.01) and reduced haloperidol (P < 0.001) by an average of 28.5% +/- 83.3% and 160.8% +/- 288.9%, respectively. However, there were marked interindividual variations in the interactive effects of chlorpromazine. The authors analyzed the importance of five CYP2D6 genotypes, *1/ *1, *1/ *10, *10/ *10, *1/*5, and *5/*10 on the percentage of change in plasma concentrations of haloperidol and reduced haloperidol. Patients with the CYP2D6*5 allele (n = 4) showed a significantly smaller increase in plasma concentrations of haloperidol (P < 0.05) and a slightly smaller increase in those of reduced haloperidol (P = 0.074) in response to the coadministration of chlorpromazine compared than those with the CYP2D6*1/*1 genotype (n = 8). Those with the CYP2D6*1/*1 genotype (n = 8) showed a trend toward greater increases in plasma concentrations of haloperidol than those with other genotypes (P = 0.087).

Adult↗
PubMed2000

CYP2D6*10 alleles are not the determinant of the plasma haloperidol concentrations in Asian patients.

The authors we investigated the relationship between plasma levels of haloperidol (HAL) and the number of CYP2D6*10 (*10) alleles in 66 Japanese inpatients with schizophrenia (male = 61, female = 5) on HAL. Plasma HAL level was determined by an enzyme immunoassay method. Daily dose of HAL was 1.5-36 (mean +/- SD = 12.3 +/- 7.6) mg or 0.02-0.49 (0.21 +/- 0.13) mg/kg body weight. Plasma HAL levels ranged from 1.4 to 47.4 (12.4 +/- 9.5) ng/mL. No significant difference in the plasma HAL levels was observed between the subjects with no, one, and two *10 alleles (one-way analysis of variance: 56.1 +/- 20.3, 61.0 +/- 20.3, and 63.3 +/- 20.3 ng/mL/mg/kg, respectively, F(2,63) = 0.65, p = 0.52). These results are not supportive of the previous report that plasma HAL levels can be predicted by the number of *10 alleles in Asian patients.

Adult↗
PubMed2000

Metabolism of desipramine in Japanese psychiatric patients: the impact of CYP2D6 genotype on the hydroxylation of desipramine.

We investigated the impact of the genotype of CYP2D6 on the hydroxylation of desipramine in eighteen patients who were administered desipramine hydrochloride per os. Significantly higher plasma concentration of desipramine/daily dose of desipramine/body weight was observed in the subjects with two mutated alleles than in the subjects with either no mutated alleles or one mutated allele (two mutated alleles versus no mutated alleles=530.4+/-215.2 versus 118.1+/-63.9 ng/ml/mg/kg, t=5.68, P<0.001; two mutated alleles versus one mutated allele=530.4+/-215.2 versus 176.2+/-62.3 ng/ml/mg/kg, P<0.001; One-way analysis of variance followed by Bonferroni's multiple comparison test, respectively). Significantly higher ratio of desipramine/2-hydroxy-desipramine was observed in the subjects with two mutated alleles compared to subjects with no mutated alleles or the subjects with one mutated allele (two mutated alleles versus one mutated allele= 4.39+/-0.36 versus 2.00+/-0.64, t=5.12, P<0.001; two mutated alleles versus no mutated alleles=4.39+/-0.36 versus 2.02+/-0.59, t=4.42, P<0.01). The genotyping of CYP2D6 only grossly predicts the steady state concentration of desipramine, mainly predicts the risk of getting very high plasma levels. Within each genotype there is marked interindividual variability.

Adult↗
PubMed1999

The effect of cytochrome P450 2D6 genotypes on haloperidol metabolism: a preliminary study in a psychiatric population.

We investigated the effect of cytochrome P450 (CYP2D6) genotypes on plasma levels of haloperidol (HAL) and reduced haloperidol (RHAL) in 47 Japanese male schizophrenic inpatients being treated with HAL. Mutation-specific polymerase chain reaction (PCR) analysis was used to detect CYP2D6*10 as the C188C1T mutation in exon 1. A long-PCR analysis method was used to detect CYP2D6*5. Allele frequencies of CYP2D6*5 and CYP2D6*10 were 4.3% and 34.0%, respectively. Plasma concentrations of HAL and RHAL were measured using high-performance liquid chromatography. The ranges of the plasma concentration of HAL and RHAL corrected to the dose were 0.28-1.60 (mean +/- SD, 0.66+/-0.25, n = 47) ng/mL/mg and 0.03-3.00 (mean+/-SD, 0.36+/-0.46, n = 47) ng/mL, respectively. Plasma RHAL/HAL ratios (R/H ratios) ranged from 0.06 to 1.88 (mean +/- SD, 0.48+/-0.32, n = 47). The analysis was performed among the four genotype groups: CYP2D6*1/CYP2D6*1 (n = 11), CYP2D6*1/CYP2D6*10 (n = 11), CYP2D6*10/CYP2D6*10 (n = 6) and those who have CYP2D6*5 allele (CYP2D6*1/ CYP2D6*5 or CYP2D6*5/CYP2D6*10 (n = 4). We observed significant tendency in effects of CYP2D6 genotypes on plasma concentration of HAL and significant effects on plasma concentration of RHAL, and R/H ratio. These results we obtained suggested that the plasma concentration of HAL and RHAL were determined partly by CYP2D6 polymorphic activity.

Adult↗
PubMed1999

Lower plasma levels of haloperidol in smoking than in nonsmoking schizophrenic patients.

The impact of smoking on plasma haloperidol (HAL) concentrations was investigated in 66 Japanese male schizophrenic inpatients treated orally with HAL. The subjects consisted of 22 nonsmokers and 44 smokers each smoking ten cigarettes per day. Plasma concentrations of HAL were determined by an enzyme immunoassay method. There were significant positive correlations between the plasma HAL concentration and the daily dose of HAL per kg body weight (Y = 58.1X-0.01 (r = 0.86)). Smokers had significantly lower HAL concentrations per daily dose of HAL/kg body weight than nonsmokers (smokers vs. nonsmokers = 54.3+/-16.6 vs. 70.6+/-23.2 ng/mL/mg/kg). In doses less than 0.2 mg/kg of HAL, smokers showed significantly lower HAL concentrations per daily dose of HAL/kg body weight than nonsmokers (smokers vs. nonsmokers = 55.1+/-14.4 vs. 79.5+/-27.1 ng/mL/mg/kg), whereas no significant difference in HAL concentrations per daily dose of HAL/kg body weight was observed between smokers and nonsmokers when treated with more than 0.2 mg/kg (smokers vs. nonsmokers = 52.9+/-20.7 vs. 60.0+/-11.1 ng/mL/mg/kg). Our results indicate that smoking may induce the enzyme(s) metabolizing HAL, which results in lower plasma HAL concentrations in smokers than in nonsmokers, particularly at low doses of HAL.

Administration, Oral↗
PubMed1998

Plasma concentrations of timiperone and its reduced metabolite in the patients on timiperone.

Plasma levels of timiperone (TIM) and reduced timiperone (RTIM) were determined in 10 schizophrenic patients who were treated with TIM. Activities of ketone reductase in red blood cells (RBC) were assayed using TIM and haloperidol (HAL) as substrates. Plasma levels of TIM and RTIM ranged from 3.2 ng/mL to 9.5 ng/mL and from 1.7 ng/mL to 7.6 ng/mL, respectively, and approximately four-fold inter-individual variations in RTIM/TIM (0.37-1.43, 0.67 +/- 0.25) were observed. There were significant and positive correlations between plasma levels of TIM or RTIM with the daily doses of TIM (mg/kg body weight); TIM (ng/mL)= 19.5 x daily dose of TIM (mg/kg) + 1.3, r = 0.79, n = 18, P < 0.01; RTIM (ng/mL) = 13.1 x daily dose of TIM (mg/kg) + 0.7, r = 0.73, n = 18, P < 0.001). Given 0.3 mg/kg of TIM, a plasma level of TIM as 7.15 ng/mL was predicted, which is approximately 60% that of HAL. The activity of TIM reductase in RBC was determined as approximately 70% of HAL reductase in RBC, although the correlation between the activities of TIM reductase and HAL reductase in RBC was high (r = 0.98, n = 10, P < 0.001).

Adolescent↗
PubMed1995

[Malnutrition].

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Adult↗
PubMed1992

Local anesthetic-sensitive electrodes: preparation of coated-wire electrodes and their basic properties in vitro.

Coated-wire electrodes with local anesthetic (LA) cation-selective membranes were prepared, and their properties in vitro were investigated. Copper wires (0.8-mm diameter) were coated with gel membranes of 110 mg of poly(vinyl chloride), 5 mg of ion pairs of tetraphenylborate anion with LA cation, 100 mg of dioctylphtalate, and 1.5 mL of tetrahydrofuran. This was the composition determined to be most suitable. Their electromotive force relative to an Ag/AgCl electrode was measured in LA solutions. The lidocaine, dibucaine, and mepivacaine electrodes all showed good Nernstian response at 25 degrees C in aqueous solutions in the concentration ranges of 1 x 10(-4) to 1 x 10(-2) mol/L, 4 x 10(-5) to 1 x 10(-2) mol/L, and 5 x 10(-5) to 1 x 10(-2) mol/L, respectively. The response time was within 10 s. The electrode potential decreased as the pH in the solution increased, with a corresponding decrease of the protonated form of LA. The hydrophobic nature of the LA was closely related to the electromotive force and to the selectivity of the electrode toward various LA cations. Dibucaine, the most hydrophobic, had the highest electrode potential. The more hydrophobic the LA of the electrode, the less it is interfered with by other LA molecules. The more hydrophobic the interferent cation, the more it acts on the electrode potential. The electrode system could also measure LA in human plasma at 37 degrees C, although the responsiveness was depressed in the low concentration range owing to binding of LA to the serum protein.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthetics, Local↗
PubMed1991

[A case of hysterical conversion manifested by pain in face and head].

We report a case of hysterical conversion, which was initially diagnosed as trigeminal neuralgia. The pain in the face and head which the patient complained seemed to be consistent with symptoms of trigeminal neuralgia. But it could not be relieved by repeated peripheral nerve blocks and even by Gasserian blocks. Failure to relieve pain by such blocks and concomitant hemifacial spasm with closure of the eye appeared to afford indication of microvascular decompression surgery. Injection of edrophonium before operation, for the purpose of differential diagnosis of myasthenic ptosis, made the patient free from all symptoms, i.e. facial pain, spasm, and ptosis. The diagnosis of hysterical conversion was made on this irrational episode. When we looked back the total clinical course, it was revealed that the patient's complaints and symptoms had been rather atypical, too various, and not anatomical. We also confirmed that various other episodes of this patient which had not received our attention during treatment were psychological features of hysteria, but we could not make his psychological stress clear, which had been in the background of hysterical conversion.

Conversion Disorder↗
PubMed1990

[Relationship between three phase bone scintigram and prognosis after sympathetic blockade in reflex sympathetic dystrophy of the hand].

We attempted to correlate the changes in three phase bone scintigram (TPBS) with prognosis after sympathetic blockade in reflex sympathetic dystrophy (RSD) of the hand. Subjects were 12 patients of RSD in acute or dystrophic stage, who all had increased images on TPBS. Either intravenous regional sympathectomy with guanethidine or stellate ganglion block was performed repeatedly. We compared TPBS obtained just before and after this series of sympathetic blocks and evaluated the eventual recovery of function of the hand. In 8 patients, blood flow (phase 1) image of TPBS decreased after the blockade. Of these patients, those who showed almost normalized tracer activity not only on flow image but on blood pool (phase 2) and delayed (phase 3) image, returned to normal. But others with normalized blood flow and still increased activity in blood pool and delayed image, remained with mild contracture of the hand. These results suggest that normalization of blood pool and delayed image on TPBS is a predictor of subsequent recovery after sympathetic blockade in RSD.

Adult↗