Biomedical subjects

K Otani

Publications and source records attributed to K Otani.

At least 73 records · Page 4Linked to original sources

PubMed1999

Relationship between bone mineral density and tooth loss in elderly Japanese women.

OBJECTIVE: To evaluate the relationship between vertebral bone mass and tooth loss and jaw bone mass in elderly Japanese women. METHODS: Mandibular cortical bone mass, alveolar bone height and number of teeth present (total, anterior, and posterior) were compared with the 3rd lumbar vertebral bone mineral density (L3BMD), measured by dual energy computed tomography (DEQCT), in 90 Japanese women by means of multiple regression analysis, controlling for body mass index, menopausal status, years since menopause and self-reported periodontal condition. RESULTS: Mandibular cortical bone mass and number of posterior teeth were associated with both alveolar bone height and L3BMD, but there was no association between alveolar bone height, number of anterior teeth present and L3BMD. CONCLUSION: Our results suggest that the loss of posterior teeth may be associated with a decrease not only in alveolar bone height, but also alveolar bone mineral density (BMD). The latter may be related to a decrease of lumbar vertebral BMD.

Adult↗

PubMed1999

Characteristics and risk factors of acute dystonia in schizophrenic patients treated with nemonapride, a selective dopamine antagonist.

The occurrence of acute dystonia was prospectively monitored in 39 schizophrenic patients (18 male and 21 female) treated with 9 to 27 mg/day of nemonapride, a selective dopamine antagonist, and the relationship of acute dystonia with characteristics of patients and plasma concentrations of the drug and prolactin was investigated. Twenty (51.3%) of 39 patients had dystonic reactions, the onsets of which occurred within 3 days after the initiation of treatment in 90% of dystonic patients. The incidence of acute dystonia was significantly higher in male than in female patients (77.8% vs. 28.6%, p < 0.05). Younger male patients (< or = 30 years) especially had an extremely high incidence of this side effect (91.7%). A positive correlation between prolactin response after 1 week of treatment and dystonia rating scores was found in male (Spearman rank correlation: r(s) = 0.606,p < 0.01) but not in female patients (r(s) = -0.378,p = not significant). These results suggest that young male patients have the highest risk of neuroleptic-induced dystonia. Prolactin response after 1 week of treatment as an index of dopamine blockade may reflect vulnerability to the development of acute dystonia at least in male patients treated with nemonapride.

Acute Disease↗

PubMed1999

Effects of itraconazole on the steady-state plasma concentrations of haloperidol and its reduced metabolite in schizophrenic patients: in vivo evidence of the involvement of CYP3A4 for haloperidol metabolism.

The effects of itraconazole, a potent inhibitor of cytochrome P450 (CYP) 3A4, on the steady-state plasma concentrations of haloperidol and reduced haloperidol were examined in schizophrenic patients. Thirteen schizophrenic patients treated with haloperidol 12 or 24 mg/day received 200 mg/day of itraconazole for 7 days. Plasma concentrations of haloperidol and reduced haloperidol were measured by high-performance liquid chromatography together with clinical assessment by the Brief Psychiatric Rating Scale (BPRS) and the Udvalg for Kliniske Undersogelser side effect rating scale just before and during itraconazole treatment and 1 week after its discontinuation. Plasma concentrations of haloperidol and reduced haloperidol during the itraconazole treatment (16.9 +/- 11.2 and 6.1 +/- 6.6 ng/mL, respectively) were significantly (p < 0.01) higher than those observed before itraconazole treatment (13.0 +/- 7.9 and 4.9 +/- 5.1 ng/mL) or 1 week after its discontinuation (13.5 +/- 8.2 and 4.9 +/- 5.0 ng/mL). No change was found in clinical symptoms assessed by BPRS, whereas neurologic side effects were significantly (p < 0.05) increased during itraconazole coadministration. The elevated plasma concentrations of haloperidol and reduced haloperidol during itraconazole coadministration were likely due to the inhibitory effects of itraconazole on the metabolism of haloperidol and reduced haloperidol. Thus, this study may provide in vivo evidence of involvement of CYP3A4 in the metabolism of haloperidol and possibly in that of reduced haloperidol. Deterioration of neurologic side effects during itraconazole treatment may result from the increased plasma concentrations of haloperidol and reduced haloperidol during itraconazole treatment.

Adult↗

PubMed1999

Lack of significant pharmacokinetic interaction between haloperidol and grapefruit juice.

The effects of repeated ingestion of grapefruit juice, an inhibitor of cytochrome P4503A4 (CYP3A4), on the steady-state plasma concentrations of haloperidol and reduced haloperidol were examined. Twelve schizophrenic inpatients receiving haloperidol 12 mg/day, ingested grapefruit juice 600 ml/day for 7 days. Blood samples were collected before and during grapefruit juice coadministration and 1 week after its discontinuation together with an assessment of clinical status. Plasma drug concentrations were measured using high-performance liquid chromatography. Clinical status for each patient was assessed by the Brief Psychiatric Rating Scale (BPRS) and the UKU side-effect rating scale (UKU). Plasma concentrations of haloperidol and reduced haloperidol during grapefruit juice coadministration (9.0 +/- 3.0 and 2.6 +/- 1.4 ng/ml, respectively) were not significantly different from those before grapefruit juice coadministration (9.1 +/- 2.8 and 2.6 +/- 1.5 ng/ml) or those 1 week after its discontinuation (8.8 +/- 2.7 and 2.6 +/- 1.3 ng/ml). There was no change in the scores of BPRS or UKU during the study period. The present results shows that grapefruit juice does not affect the plasma concentrations of haloperidol and reduced haloperidol or clinical status in patients receiving haloperidol.

Adult↗

PubMed1999

Nucleus pulposus-induced nerve root injury: relationship between blood flow and motor nerve conduction velocity.

OBJECTIVE: It is well known that nucleus pulposus induces nerve root injury. The aim of this study was to assess the relationship between intraneural blood flow and motor nerve conduction velocity (NCV) after incision of the adjacent disc. METHODS: A total of 65 dogs were used. A left hemilaminotomy was performed, the annulus fibrosus of the L6-L7 intervertebral disc was incised, and nucleus pulposus was gently pushed into the epidural space by saline solution injection. A left hemilaminotomy without disc incision was used as the sham operation. Seven dogs were used for incision and five dogs for sham treatment for each of the following time points: 1 day, 3 days, 1 week, 1 month, and 2 months of exposure. Five additional dogs were used to establish baseline data. Blood flow in the nerve root was measured in the left L7 nerve root with a tissue blood flowmeter, using an electrolytic hydrogen clearance method. Motor NCV over the exposed area of the nerve root was measured using a neurophysiological technique. RESULTS: There was a reduction in blood flow in the nerve root after disc incision that began after 1 day and was maximal after 1 week. This reduction had resolved by 1 month, however. The motor NCV showed a reduction pattern similar to that for blood flow in the nerve root, but reduction did not begin until 3 days after disc incision and was not fully resolved until 2 months. CONCLUSION: This study demonstrates that the reduction and recovery of motor NCV are related to, and preceded by, a reduction in blood flow in the nerve root. The data might provide important information regarding the basic pathophysiological mechanisms of nucleus pulposus-induced nerve root injury.

Animals↗

PubMed1999

Effects of carbamazepine coadministration on plasma concentrations of the enantiomers of mianserin and of its metabolites.

Concentrations of the enantiomers of unconjugated and of total (unconjugated plus conjugated) mianserin, desmethylmianserin and 8-hydroxymianserin were measured in 12 patients before and after the introduction of carbamazepine. The dose of mianserin was 60 mg/d, carbamazepine was coadministered at 400 mg/d for 4 weeks, and blood samples were taken at weekly intervals after the introduction of carbamazepine. Each week, carbamazepine significantly decreased plasma concentrations of unconjugated and total (S)-mianserin (the more potent enantiomer) and of unconjugated and total (R)-mianserin. On average, plasma concentrations of unconjugated and total (S)-mianserin and of unconjugated and total (R)-mianserin were 55%, 56%, 66%, and 55%, respectively, of the corresponding values before introduction of carbamazepine. These results strongly suggest the involvement of CYP3A4, the major CYP enzyme induced by carbamazepine, in the metabolism of both enantiomers of mianserin. A strong decrease in the concentrations of (S)-8-hydroxymianserin was also measured (on average, the concentrations were 69% of the corresponding values before carbamazepine introduction). Conversely, plasma concentrations of unconjugated and of total (S)-desmethylmianserin, (R)-desmethylmianserin, and (R)-8-hydroxymianserin were only slightly modified by carbamazepine. From a clinical point of view, as a therapeutic window for (S)-mianserin has been recently suggested, the dose of racemic mianserin for a patient whose (S)-mianserin concentrations have been stabilized within this therapeutic window would need to be approximately doubled if carbamazepine, at 400 mg/d, is introduced as a comedication.

Adult↗

PubMed1999

No pharmacokinetic but pharmacodynamic interactions between cisapride and bromperidol or haloperidol.

Pharmacokinetic and pharmacodynamic interactions between the gastrokinetic drug cisapride and the antipsychotic drugs bromperidol and haloperidol were studied in 29 schizophrenic inpatients. Fourteen patients were taking bromperidol (12-24 mg/d), and 15 were taking haloperidol (12-36 mg/d). Cisapride 10 mg/d was coadministered for 1 week, and blood sampling was performed before cisapride treatment, 1 week after starting cisapride treatment, and I week after stopping cisapride treatment. On the same days as the blood sampling, psychotic symptoms and side effects were evaluated using the Brief Psychiatric Rating Scale (BPRS) and the Udvalg for Kliniske Undersøgelser (UKU) side effect rating scale (UKU), respectively. Plasma concentrations of bromperidol, haloperidol, and their reduced metabolites were measured by high-performance liquid chromatography. The mean BPRS scores after adding cisapride were significantly higher than those before cisapride (p<0.01) and after stopping cisapride (p<0.001) in the haloperidol group in this uncontrolled study. A similar tendency was observed in the bromperidol group, although it did not reach statistical significance (p = 0.08). Cisapride coadministration caused no significant changes in the mean plasma concentrations of bromperidol, haloperidol, and their reduced metabolites or in the mean UKU score. The present study suggests that there is no significant pharmacokinetic interaction between cisapride and bromperidol or haloperidol, but cisapride appears to deteriorate psychotic symptoms by a pharmacodynamic interaction in schizophrenic patients treated with haloperidol.

Antipsychotic Agents↗

PubMed1999

Ictal video-EEG recording of three partial seizures in a patient with the benign infantile convulsions associated with mild gastroenteritis.

PURPOSE: In infants, benign convulsions can be triggered by febrile illness or mild diarrhea such as Rotavirus gastroenteritis. The triggering mechanism of these convulsions is still unknown. In spite of several reports concerning clinical features, the ictal EEG recordings were rarely analyzed by a video-EEG monitoring system. To reveal a clue for the triggering mechanism of these convulsions, we analyzed the correlation of clinical manifestations and the EEG discharges during the ictal events and compared with previous reports. METHODS: The ictal EEG of a cluster of three afebrile convulsions associated with mild gastroenteritis was recorded by an EEG closed-circuit TV (EEG-CCTV) monitoring system in a 6-month-old healthy female infant. RESULTS: All seizures began as complex partial seizures (CPSs), which exhibited a motionless stare with or without leftward deviation of both eyes, and evolved to secondarily generalized tonic-clonic seizures (SGTCSs) for approximately 90 s. Each of three ictal discharges began from the right occipital, right centroparietotemporal, and left occipital regions, respectively. CONCLUSIONS: Although initiating sites of ictal discharges of benign infantile convulsions associated with mild gastroenteritis (BICE) were previously reported to be variable among patients, these results indicated that those differ among seizures even in a same infant.

Cerebral Cortex↗

PubMed1999

Clomipramine treatment of delusional disorder, somatic type.

Four patients of delusional disorder, somatic type, were treated with clomipramine 60-120 mg/day. All patients showed marked clinical improvement after 27-57 days of clomipramine treatment. In one case, previous treatments by various antipsychotic drugs including pimozide had been unsuccessful. This report suggests that clomipramine is effective at least for some patients with delusional disorder, somatic type, including pimozide-resistant cases. It is also suggested that there is some association between delusional disorder, somatic type, and serotonergic dysfunction.

Adult↗

PubMed1998

Effects of various factors including the CYP2D6 genotype and coadministration of flunitrazepam on the steady-state plasma concentrations of bromperidol and its reduced metabolite.

The effects of various factors, including the cytochrome P450 (CYP) 2D6 genotype and the coadministration of flunitrazepam, on the steady-state plasma concentrations (Css) of bromperidol and its reduced metabolite were studied in 62 schizophrenic inpatients receiving bromperidol 12 mg/day. By use of allele-specific PCR analysis, the wild type allele (CYP2D6*1A) and four mutated alleles causing either absent (CYP2D6*3, CYP2D6*4 and CYP2D6*5) or decreased (CYP2D6*10) CYP2D6 activity were identified. The means (ranges) of the Css of bromperidol and reduced bromperidol corrected to the median body weight were 7.2 (1.3-17.4) and 2.2 (0.4-8.9) ng/ml, respectively. Neither the Css of bromperidol nor that of reduced bromperidol significantly differed among the patients with no (n = 28), one (n = 30) and two mutated alleles (n = 4). The patients coadministered with flunitrazepam (n = 52) had significantly (P < 0.05) higher Css of bromperidol, but not reduced bromperidol, than those not (n = 10). Age, sex and smoking had no significant effects on the Css of these compounds. The present study thus suggests that the polymorphic CYP2D6 is not involved in the metabolism of bromperidol and reduced bromperidol to a major extent. The coadministration of flunitrazepam inhibits the metabolism of bromperidol, but age, sex and smoking do not affect it.

Adolescent↗

PubMed1998

Effect of itraconazole on the single oral dose pharmacokinetics and pharmacodynamics of alprazolam.

To assess the effect of itraconazole, a potent inhibitor of cytochrome P450 (CYP) 3A4, on the single oral dose pharmacokinetics and pharmacodynamics of alprazolam, the study was conducted in a double-blind randomized crossover manner with two phases of treatment with itraconazole-placebo or placebo-itraconazole. Ten healthy male subjects receiving itraconazole 200 mg/day or matched placebo orally for 6 days took an oral 0.8 mg dose of alprazolam on day 4 of each treatment phase. Plasma concentration of alprazolam was measured up to 48 h after alprazolam dosing, together with the assessment of psychomotor function by the Digit Symbol Substitution Test, Visual Analog Scale and Udvalg for kliniske undersøgelser side effect rating scale. Itraconazole significantly (P < 0.01) increased the area under the concentration-time curves from 0 h to infinity (252 +/- 47 versus 671 +/- 205 ng h/ml), decreased the apparent oral clearance (0.89 +/- 0.21 versus 0.35+/-0.10 ml/min per kg) and prolonged the elimination half-life (15.7 +/- 4.1 versus 40.3 +/- 13.5 h) of alprazolam. The test performed during itraconazole treatment showed significantly depressed psychomotor function. It is suggested that itraconazole, a potent CYP3A4 inhibitor, increases plasma concentration of alprazolam via its inhibitory effects on alprazolam metabolism. Thus, this study supports previous studies suggesting that CYP3A4 is the major enzyme catalyzing the metabolism of alprazolam. Enhanced side effects of alprazolam by itraconazole coadministration were probably reflected by these pharmacokinetic changes.

Administration, Oral↗

PubMed1998

Correlation between steady-state plasma concentrations of mianserin and trazodone in depressed patients.

OBJECTIVE: The correlations between steady-state plasma concentrations of mianserin and its active metabolite desmethylmianserin and those of trazodone and its active metabolite m-chlorophenylpiperazine (m-CPP) were examined in 19 depressed patients. METHODS: Ten patients received first mianserin (30 mg per day) and second trazodone (150 mg per day), while 9 patients received these treatments in the opposite sequence, with at least 2-week intervals between the two phases. Blood was sampled at steady state, 1-3 weeks after initiation of each treatment. Plasma concentrations of mianserin, the separate enantiomers S(+)- and R(-)-mianserin, desmethylmianserin, trazodone and m-CPP were measured by means of high-performance liquid chromatography. RESULTS: There was a significant correlation between steady-state plasma concentrations of trazodone and total mianserin (r = 0.59) or S(+)-mianserin (r = 0.57), but not R(-)-mianserin (r = 0.33). CONCLUSION: The present study thus suggests that the metabolic capacity of mianserin, especially the more active S(+)-enantiomer, and that of trazodone correlate to each other. This finding supports the previous suggestions that cytochrome P4502D6 is involved in the metabolism of mianserin and trazodone.

Antidepressive Agents, Second-Generation↗

PubMed1998

Correlation between steady-state plasma concentrations (Css) of bromperidol and haloperidol.

1. Bromperidol is a close structural analogue of haloperidol, and its metabolic pathways are similar to those of haloperidol. The authors studied the correlation between the Css of bromperidol and haloperidol. 2. The subjects were 16 schizophrenic inpatients. Fourteen patients received firstly bromperidol 12 mg/day and secondly haloperidol 12 mg/day, while the remaining two patients received the two treatments in the opposite sequence. 3. Blood samplings were performed 2-3 weeks after the initiation of each treatment, and the Css of bromperidol, haloperidol and their reduced metabolites were measured by high-performance liquid chromatography. 4. Neither the correlation between the Css of bromperidol and haloperidol (r = 0.246) nor that between the Css of reduced bromperidol and reduced haloperidol (r = 0.142) was significant. 5. The present study thus suggests that the Css of bromperidol and haloperidol do not correlate well in individuals.

Adult↗

PubMed1998

Effect of carbamazepine on the single oral dose pharmacokinetics of alprazolam.

The effect of carbamazepine, an inducer of cytochrome P450 (CYP) 3A4, on the single oral dose pharmacokinetics of alprazolam was examined in a double-blind, randomized crossover study with two phases. Seven healthy male subjects took carbamazepine 300 mg/day or matched placebo orally for 10 days, and on the 8th day they took a single oral 0.8 mg dose of alprazolam. Blood samples were taken and psychomotor function was assessed by the Digit Symbol Substitution Test, Visual Analog Scale, and UKU Side Effect Rating Scale up to 48 h after alprazolam dosing. Carbamazepine significantly (p < .01 to .001) decreased the plasma alprazolam concentrations during the elimination phase. Carbamazepine significantly (p < .001) increased the apparent oral clearance (0.90 +/- 0.21 vs. 2.13 +/- 0.54 ml/min/kg) and shortened the elimination half-life (17.1 +/- 4.9 vs. 7.7 +/- 1.7 h), with no significant effect on the peak plasma concentration (11.7 +/- 1.5 vs. 13.0 +/- 3.5 ng/ml). The majority of psychomotor function parameters during the carbamazepine treatment were not significantly different from those during the placebo treatment, probably because of the sedative effect of carbamazepine itself. The present study suggests that carbamazepine decreases plasma concentration of alprazolam by inducing its metabolism. It also supports the previous studies, suggesting that alprazolam is metabolized predominantly by CYP3A4.

Adult↗

PubMed1998

Single oral dose kinetics of zotepine and its relationship to prolactin response and side effects.

The authors investigated the single oral dose kinetics of zotepine and its relationship with prolactin response and side effects in 14 healthy male volunteers. Each subject took a single oral 25-mg dose of zotepine, and plasma concentrations of zotepine, prolactin, and their side effects were monitored up to 36 hours after dosing. The means +/- SD of the time of maximal plasma concentration (tmax), the apparent oral clearance, the apparent volume of distribution, and the elimination half-life (t1/2) were 3.8 +/- 1.2 hours, 4.6 +/- 4.2 1/h.kg, 109.0 +/- 59.0 1/kg, and 21.0 +/- 8.9 hours, respectively. The change in prolactin concentrations and side effect scores were parallel with that of drug concentrations, although no significant correlation was found between these three parameters at any time-point. The current results clearly indicate that the tmax and t1/2 of zotepine are much longer than those previously reported, which are reflected in the changes in prolactin concentrations and side effect scores.

Administration, Oral↗

PubMed1998

Prolactin response to bromperidol treatment in schizophrenic patients.

The prolactin response to an antipsychotic drug, bromperidol was studied in 24 schizophrenic in-patients (13 males. 11 females). Eight patients were given 6 mg/day, 8 were given 18 mg/day. Duration of treatment was 3 weeks. Plasma concentrations of bromperidol and reduced bromperidol were measured by high-performance liquid chromatography, and that of prolactin was measured by radioimmunoassay. Bromperidol treatment significantly (P < 0.01) increased plasma concentration of prolactin each week. The mean +/- S.D. of the delta-prolactin (the mean concentration during treatment minus the pretreatment concentration) was 13.3 +/- 12.4 ng/ml. Multiple regression analysis showed that the delta-prolactin concentration was significantly greater in females than in males (P < 0.05) and correlated to plasma concentrations of bromperidol (P < 0.001) and reduced bromperidol (P < 0.0001). These results suggest that the prolactin response to bromperidol treatment depend on plasma concentrations of both bromperidol and reduced bromperidol and gender, and that reduced bromperidol is involved in the pharmacological effects during bromperidol treatment.

Adult↗

PubMed1998

Polyamine metabolism of rat gastric mucosa after oral administration of hypertonic sodium chloride solution.

Oral administration of 1 ml of 3.42 M NaCl solution to rats induced spermidine/spermine N1-acetyltransferase (SSAT) activity in gastric mucosa as well as ornithine decarboxylase (ODC) activity. SSAT activity increased and peaked at 5 h and again at 7 h, whereas ODC activity peaked at 6 h. SSAT mRNA also increased after 3.42 M NaCl administration to an extent similar to the increase in SSAT activity at 5 h. Intracellular putrescine level and DNA synthesis were increased by NaCl administration. A polyamine oxidase inhibitor, N,N'-bis(2,3-butadienyl)-1,4-butanediamine (MDL-72527), but not an ODC inhibitor, alpha-difluoromethylornithine (DFMO), inhibited the increases in putrescine level and DNA synthesis at 5 h. The inhibition of DNA synthesis by MDL-72527 was reversed by putrescine administration. In contrast, both MDL-72527 and DFMO inhibited the increase in putrescine level and DNA synthesis at 16.5 h. These findings suggest that putrescine produced from preexistent spermidine by SSAT is responsible for the initial DNA synthesis after mucosal injury induced by NaCl and that both SSAT and ODC are involved in formation of putrescine, which is required for subsequent DNA synthesis.

Acetyltransferases↗

PubMed1998

Effects of the novel tricyclic quinoxalinedione derivatives, SM-18400 and its analogs, on N-methyl-D-aspartate (NMDA) receptor-mediated synaptic transmission in the isolated neonatal rat spinal cord in vitro.

We examined the effects of novel tricyclic quinoxalinedione derivatives, SM-18400 ((S)-9-chloro-5-[p-aminomethyl-o-(carboxymethoxy)phenylcarbamoylmethy l]-6,7-dihydro-1H,5H-pyrido[1,2,3-de]quinoxaline-2,3-dione hydrochloride trihydrate) and its analogs (i.e., ID-17263 and ID-17332), on the N-methyl-D-aspartate (NMDA) receptor-mediated polysynaptic reflex (PSR) in the isolated spinal cord of neonatal rats in vitro. Application of SM-18400 selectively suppressed the PSR activity in a concentration-dependent manner without affecting the monosynaptic reflex (MSR). Differential suppression of the PSR was also obtained with ID-17263, ID-17332 and other known NMDA receptor glycine-binding site antagonists, 5,7-dichlorokynurenate (5,7-diClkyn) and L-689,560 (4-trans-2-carboxy-5,7-dichloro-4-phenylaminocarbonylamino-1,2,3,4 -tetrahydroquinoline). Relative potencies of the test drugs for inhibition of the PSR were as follows: SM-18400 >> L-689,560 > ID-17332 > ID-17263 > 5,7-diClkyn. In addition, the inhibitory effects of SM-18400 on PSR were markedly antagonized by simultaneous application of D-serine, an agonist for NMDA receptor glycine-binding sites. These findings suggest that SM-18400 is a potent NMDA receptor glycine-binding site antagonist and blocks the NMDA receptor-mediated synaptic neurotransmission in the spinal cord in vitro.

Aminoquinolines↗