Plasma Levels Of Risperidone Research Articles

Plasma Concentrations of Risperidone and Olanzapine during Coadministration with Oxcarbazepine

Oxcarbazepine (OZC) is a second-generation antiepileptic drug (AED) that also may be used as a mood stabilizer. Unlike carbamazepine (CBZ), which is an inducer of the cytochrome P-450 isoforms and may accelerate the elimination of several therapeutic agents, OXC seems to have only a modest inducing action. The aim of this investigation was to evaluate the effect of a treatment with OXC on plasma concentrations of the new antipsychotics risperidone and olanzapine. OXC, at a dosage of 900-1,200 mg/day, was administered for 5 consecutive weeks to 25 outpatients, 10 men and 15 women, aged 25 to 64 years, with bipolar or schizoaffective disorder. Twelve patients were stabilized on risperidone therapy (2-6 mg/day) and 13 on olanzapine (5-20 mg/day). Steady-state plasma concentrations of risperidone and its active metabolite 9-hydroxyrisperidone (9-OH-risperidone) and olanzapine were measured by high-pressure liquid chromatography (HPLC) before addition of OXC and after 5 weeks from the start of adjunctive treatment. OXC caused only minimal and no significant changes in the mean plasma levels of risperidone (from 5.6 +/- 3.6 ng/ml at baseline to 4.8 +/- 2.6 ng/ml at week 5), 9-OH-risperidone (from 23.6 +/- 7.5 to 24.7 +/- 7.4 ng/ml), and olanzapine (from 26.5 +/- 5.7 ng/ml at baseline to 27.8 +/- 5.1 ng/ml). OXC coadministration with either risperidone or olanzapine was well tolerated. Our findings indicate that OXC does not affect the elimination of risperidone and olanzapine, thus confirming its weak inducing effect on hepatic drug-metabolizing enzymes.

Increase in Risperidone Plasma Level With Lamotrigine

Back to table of contents Previous article Next article Letter to the EditorFull AccessIncrease in Risperidone Plasma Level With LamotrigineSARA DORIS BIENENTREU, M.D., and KLAUS-THOMAS HELMUT KRONMÜLLER, M.D., SARA DORIS BIENENTREUSearch for more papers by this author, M.D., and KLAUS-THOMAS HELMUT KRONMÜLLERSearch for more papers by this author, M.D., Heidelberg, GermanyPublished Online:1 Apr 2005https://doi.org/10.1176/appi.ajp.162.4.811-aAboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail To the Editor: A combination of clozapine and risperidone is effective in treating patients with schizophrenia who are unresponsive to other atypical antipsychotics or monotherapy with clozapine (1). Nevertheless, there are patients who respond only partially or even fail to respond to this combination. Saba et al. (2) and Dursun et al. (3) reported on patients who showed a substantial improvement of persistent positive symptoms when lamotrigine was added to clozapine therapy. There is evidence supporting the positive effects of lamotrigine based on its glutamate excess-release inhibition (4).Because of these interesting reports, we decided to supplement the clozapine-risperidone combination of Ms. A, a 26-year-old inpatient who suffers from therapy-resistant schizophrenia with imperative auditory hallucinations, with lamotrigine. She had been taking clozapine, 550 mg/day, for 5 years and risperidone, 8 mg/day, for 4 weeks and had only responded partially. Her plasma levels of risperidone (55–70 ng/ml) and clozapine (800–1100 ng/ml) were stable. Her lamotrigine dose was titrated up to 250 mg/day in steps of 25 mg per week. After Ms. A had been taking 175 mg/day of lamotrigine for 5 days, her plasma level was 5 mg/liter, and her risperidone plasma level was 69 ng/ml. We further increased her dose of lamotrigine to 200 mg/day. Her risperidone level rose to 284 ng/ml, and in follow-up measures, it showed a value of 263 ng/ml. Her clozapine level rose to 1300 ng/ml. Ms. A did not have any intoxication symptoms. Because we did not assume any connection of increased plasma level of risperidone with lamotrigine, we heightened the dose to 225 mg/day. The next measurement of both plasma levels indicated an exorbitant increase of risperidone plasma level, up to 412 ng/ml. Ms. A complained of dizziness and tiredness. We quickly reduced the dose of risperidone to 2 mg/day and withdrew the drug 1 week later. An overdose of risperidone was unlikely since it was taken under supervision.Metabolism of risperidone occurs mainly in the liver and is dependent mostly on cytochrome P450 isoenzyme CYP 2D6. Lamotrigine does not inhibit CYP 2D6. It is eliminated by the kidneys after glucuronidation in the liver. Until now, we have had no explanation for the increase of the risperidone plasma level during concomitant therapy with clozapine and lamotrigine. Clinicians should be aware of this effect.

Prediction of response to risperidone treatment with respect to plasma concencentrations of risperidone, catecholamine metabolites, and polymorphism of cytochrome P450 2D6

In the present study, we examined the relationships between plasma concentrations of risperidone and clinical responses, extrapyramidal symptoms, plasma levels of cotinine and caffeine, or cytochrome (cyp)2D6 genotypes. In addition, we also investigated the relationships between plasma levels of 3-methoxy-4-hydroxyphenylglycol (MHPG) or homovanillic (HVA) acid and clinical responses to risperidone. One hundred and 36 patients (male/female: 58/78, age 37+/-13 years) who met DSM-IV criteria for schizophrenia, schizoaffective disorder, delusional disorder and brief psychotic disorder, and who were being treated with risperidone alone, were evaluated regarding their clinical improvement and extrapyramidal symptoms using the Positive and Negative Syndrome Scale (PANSS) and Simpson and Angus (SAS), respectively, and plasma levels of cotinine, caffeine, MHPG and HVA were analysed by high-performance liquid chromatography. The cyp2D6*5 and *10 alleles were identified using the polymerase chain reaction. There was a positive correlation between plasma levels of risperidone plus 9-hydroxyrisperidone (active moiety) and SAS scores, but not the PANSS. Pretreatment HVA levels in responders were higher than those in nonresponders. In addition, there was a negative correlation between changes in HVA levels and improvement in PANSS scores. There was no association between plasma levels of risperidone and plasma levels of cotinine or caffeine. Furthermore, there were no differences in the risperidone/9-hydroxyrisperidone ratio, clinical improvements and extrapyramidal symptoms among cyp2D6 genotypes. These results indicate that pretreatment HVA levels and plasma concentrations of active moiety might play a part in predicting the clinical response and occurrence of extrapyramidal symptoms, respectively, when treating patients with risperidone.

Risperidone Plasma Levels, Clinical Response and Side-Effects

Introduction: Assessment of the relation between oral neuroleptic dose, serum drug levels and clinical response may provide important information for rational treatment decisions.

Risperidone plasma levels, clinical response and side–effects

Assessment of the relation between oral risperidone dose, serum drug levels and clinical response may provide important information for rational treatment decisions. Inter-individual differences in the liver cytochrome P450 system, especially in the CYP2D6 subsystem, which account for a significant portion of risperidone metabolism, may also influence plasma drug levels and alter clinical response parameters. We thus prospectively investigated risperidone serum concentrations in relation to clinical efficacy and side-effects and genotyped major CYP2D6 polymorphisms to determine their effect upon these parameters. Neuroleptic monotherapy with risperidone was administered to schizophrenia patients in a 6-week open dose clinical trial. Weekly assessments including CGI and PANSS ratings to assess psychopathology; SAS to assess medication side effects; and blood draws to quantify steady state plasma levels of risperidone and 9-OH-risperidone were carried out. In addition, major CYP2D6 polymorphisms including alleles *4, *6 and *14 were genotyped. Eighty-two patients were recruited. Mean oral dose of risperidone was 4.3 +/- 0.9 mg. Mean plasma level of both risperidone and 9-OH-risperidone together ("active moiety") was 41.6 +/- 26.6 ng/ml. Significant improvements in PANSS scales and the various subscales ensued. There was a positive linear correlation between active moiety plasma levels and dose (r = 0.291, p = 0.015) and between risperidone and 9-OH-risperidone levels (r = 0.262; p = 0.016). Nonresponders to pharmacotherapy (PANSS-Improvement < 30%) showed significantly higher active moiety plasma levels (49.9 +/- 30.7 ng/ml) than responders (38.2 +/- 17.0 ng/ml; p = 0.045) without significantly higher oral doses (p = 0.601). Patients with longer illness duration (> or = 3 years) had significantly higher plasma drug levels than those with a shorter course (< 3 years; p = 0.039). Extrapyramidal side effects (EPS) and plasma levels were not correlated (r = 0.028; p = 0.843), but higher plasma levels at week 2 predicted an incidence for EPS (p < 0.050). Accordingly, patients initially receiving higher oral doses of risperidone were significantly more likely to respond with EPS in the trial course. Eight patients (9.8%) were heterozygous carriers of the CYP2D6 allele *4. CYP2D6 polymorphisms did not predict clinical response, but predicted a tendential increase in the plasma risperidone to 9-OH-risperidone ratio (0.5 +/- 0.6 vs. 1.9 +/- 1.8; p = 0.120). The major finding was that responders to risperidone treatment had significantly lower blood levels of risperidone and 9-OH risperidone than patients who did not respond to the treatment despite administration of similar oral doses. The observed CYP2D6 polymorphisms did not contribute to altered clinical efficacy, but affected risperidone to 9-OH-risperidone ratios. Increased plasma levels of the active moiety in patients with longer illness may represent general aging effects. Conversely, the observed higher plasma levels in nonresponders may derive from unaccounted genetic metabolism abnormalities or Phase II metabolism disturbances. Patients initially receiving higher oral risperidone doses were more likely to respond with extrapyramidal side effects which reaffirms the need for careful titration. The high inter-individual variability in risperidone and 9-OH-risperidone metabolization and the relationship between clinical outcome and plasma levels warrants regular plasma level monitoring of both compounds to assess for the clinically relevant active moiety.

Small effects of low dosage levomepromazine on plasma risperidone levels in a steady state

Yoshimura, Reiji; Shinkai, Koji; Kakihara, Shingo; Kaji, Kyoko; Yamada, Yasuhisa; Goto, Makiko; Ueda, Nobuhisa; Nakamura, Jun Author Information

Intra- and interindividual variations in steady-state plasma concentrations of risperidone and 9-hydroxyrisperidone in schizophrenic patients treated chronically with various doses of risperidone.

The intra- and interindividual variability in apparent steady-state plasma levels of risperidone (RSP) and its metabolite 9-hydroxyrisperidone (9-OHRSP) in schizophrenic patients was investigated. Patients (n = 46, age 26.4 +/- 5.3 years) with diagnosed schizophrenia were treated with a fixed daily oral dose of RSP (1-12 mg/d). The steady-state plasma samples from these patients were collected over a period of 5 years and a total of 549 visits. Plasma concentrations of RSP and 9-OHRSP were determined using a highly sensitive and specific LC-MS-MS method with a detection limit of 0.1 ng/mL. All plasma samples had measurable amounts of 9-OHRSP; however, RSP was nondetectable (<0.1 ng/mL) in 18% of the plasma samples. 9-OHRSP levels were, on average, approximately 22 times higher than those of RSP. The plasma levels of RSP and 9-OHRSP varied widely among patients receiving similar doses of RSP, and the intra- and interindividual variations of RSP and 9-OHRSP plasma levels were found to be large. The data indicated that there was no significant change in the steady-state levels of either RSP or 9-OHRSP during the treatment period. Similarly, the dose-normalized concentration did not vary significantly during the treatment period or with the administered dose. The absence of RSP in many plasma samples (<0.1 ng/mL) and presence of 9-OHRSP at severalfold higher concentrations than RSP indicate that measuring plasma levels of RSP alone may lead to erroneous interpretation in plasma level monitoring studies. The current data support the fact that it is important to measure steady-state levels of total active moiety by analyzing both RSP and 9-OHRSP for plasma drug monitoring.

Estudio de biodisponibilidad comparativa de dos formulaciones de risperidona existentes en el mercado chileno

Bioavailability of a particular drug can vary according to the formulation used. Therefore, studies of comparative bioavailability of different formulations of a same drug are worthwhile. To compare the bioavailability of two risperidone formulations available in the Chilean market. The bioavailability of a local risperidone formulation (Spiron) was compared with the original formulation of the drug (Risperdal) in 12 healthy volunteers, aged 19 +/- 1 years. A single dose of 3 mg was given orally, using a randomized double blind protocol in two periods. Fifteen blood samples were obtained at regular intervals, until 24 h after drug administration. Risperidone plasma levels were measured by high pressure liquid chromatography. pharmacokinetic parameters were calculated using a computer program that is independent of compartmental analysis. The area under the curve of plasma concentration versus time, from 0 to infinite (ABC0-infinity) and from 0 to 24 h (ABC0-24), early exposure (ABC from 0 to maximal time) and maximal plasma concentrations were significantly lower for Spiron. Half life time and time to achieve the maximal concentration were similar for the two formulations. According to bioequivalence tests suggested by the Food and Drug Administration (FDA) of the United States (90% confidence interval for the difference of long transformed mean pharmacokinetic parameters), the formulations Risperdal and Spiron, cannot be considered interchangeable.

Inhibition of risperidone metabolism by fluoxetine in patients with schizophrenia: a clinically relevant pharmacokinetic drug interaction.

The effect of fluoxetine on the steady-state plasma concentrations of risperidone and its active metabolite 9-hydroxyrisperidone (9-OH-risperidone) was evaluated in 10 patients with schizophrenia or schizoaffective disorder. Patients stabilized on risperidone (4-6 mg/day) received additional fluoxetine (20 mg/day) to treat concomitant depression. One patient dropped out after 1 week due to the occurrence of akathisia associated with markedly increased plasma risperidone concentrations. In the other subjects, mean plasma concentrations of risperidone increased during fluoxetine administration from 12 +/- 9 ng/mL at baseline to 56 +/- 31 at week 4 (p < 0.001), while the levels of 9-OH-risperidone were not significantly affected. After 4 weeks of combined treatment, the levels of the active moiety (sum of the concentrations of risperidone and 9-OH-risperidone) increased by 75% (range, 9-204%, p < 0.01) compared with baseline. The mean plasma risperidone/9-OH-risperidone ratio also increased significantly. During the second week of adjunctive therapy, two patients developed Parkinsonian symptoms, which were controlled with anticholinergic medication. These findings indicate that fluoxetine, a potent inhibitor of the cytochrome P450 enzyme CYP2D6 and a less potent inhibitor of CYP3A4, reduces the clearance of risperidone by inhibiting its 9-hydroxylation or alternative metabolic pathways. This interaction may lead to toxic plasma risperidone concentrations. In addition to careful clinical observation, monitoring plasma risperidone levels may be of value in patients given adjunctive therapy with fluoxetine.

Risperidone metabolism in relation to CYP2D6*10 allele in Korean schizophrenic patients.

Risperidone is known to be biotransformed to its active metabolite, 9-hydroxyrisperidone, by the polymorphic CYP2D6 in Caucasians. This study aimed to investigate the relationship between the CYP2D6*10 allele and the plasma levels of risperidone and 9-hydroxyrisperidone in Korean schizophrenic patients. Eighty-two Korean schizophrenic patients in monotherapy with oral doses of risperidone from 1 mg/day to 8 mg/day (mean +/- SD 4.3 +/- 1.9, median 4) participated in this study. Plasma concentrations of risperidone and 9-hydroxyrisperidone were analyzed using high-performance liquid chromatography. The CYP2D6*10 allele, which contains C188T mutation in exon 1, was identified using allele-specific polymerase chain reaction amplification. Seventeen of 82 patients were homozygous for CYP2D6*1, 22 for *10, while the remaining 43 patients were heterozygous for these alleles. The plasma levels of risperidone and 9-hydroxyrisperidone ranged from 1.0 nM to 168 nM and 6.2 nM to 235 nM, respectively. The median concentrations/dose (C/Ds) (range) of risperidone in CYP2D6*1/*1, *1/*10, and *10/*10 groups were 1.7 (0.2-7.9), 2.6 (0.3-27.1), and 6.7 nM/mg (2.4-21.0), respectively. There was a statistically significant difference among the three genotypes (Kruskal-Wallis test, P<0.001). For 9-hydroxyriperidone, the corresponding median C/Ds were 13.1 (3.3-25.4), 11.9 (4.2-30.8), and 13.6 nM/mg (6.5-52.8), respectively, with no significant difference between the genotypes (P=0.54). The medians of the ratios between risperidone and 9-hydroxyrisperidone concentrations were 0.13 (0.01-0.93), 0.28 (0.01-2.77), and 0.46 nM/mg (0.05-1.28) in *1/*1, *1/*10, and *10/*10 genotypes, respectively, and they were significantly different (P=0.004). The active moieties (sum of the C/Ds of risperidone and 9-hydroxyrisperidone) were not significantly different between the genotypes (P=0.063). In Korean schizophrenic patients, the metabolism of risperidone is dependent on CYP2D6, and the CYP2D6*10 allele is important for the regulation of the activity of this enzyme. There were no significant differences in the plasma concentration of parent drug plus its active metabolite between the genotypes. This suggests that the clinical significance of this polymorphism is limited. Our study confirms previous studies on risperidone metabolism in Caucasians.

Possible Relationship between Combined Plasma Concentrations of Risperidone plus 9-Hydroxyrisperidone and Extrapyramidal Symptoms

We investigated the relationships between extrapyramidal symptoms (EPS) induced by risperidone, the dosage of risperidone and the combined plasma concentrations of risperidone plus its active metabolite, 9-hydroxyrisperidone, in 20 schizophrenic patients. There was a positive correlation between the scores on the Simpson and Angus Scale and both the dosage of risperidone and the sum of the plasma levels of risperidone and 9-hydroxyrisperidone. These results suggest that EPS induced by risperidone increase in conjunction with both the dosage of risperidone and the total plasma concentrations of the parent compound and its active metabolite.

Plasma concentrations of risperidone and 9-hydroxyrisperidone during combined treatment with paroxetine.

The effects of paroxetine on steady-state plasma concentrations of risperidone and its active metabolite 9-hydroxyrisperidone (9-OH-risperidone) were studied in 10 patients with schizophrenia or schizoaffective disorder. Patients stabilized using risperidone therapy (4-8 mg/d) also received paroxetine (20 mg/d) for 4 weeks. During paroxetine administration, mean plasma concentrations of risperidone increased significantly (P < 0.01), whereas levels of 9-OH-risperidone decreased slightly but not significantly. After 4 weeks of paroxetine treatment, the sum of the concentrations of risperidone and 9-OH-risperidone (active moiety) increased significantly by 45% (P < 0.05) over baseline. The mean plasma risperidone/9-OH-risperidone ratio was also significantly modified (P < 0.001) during paroxetine treatment. The drug combination was generally well tolerated with the exception of one patient who developed Parkinsonian symptoms in the second week of adjunctive therapy. In this patient total plasma levels of risperidone and its active metabolite increased by 62% during paroxetine co-administration. The authors' findings indicate that paroxetine, a potent inhibitor of CYP2D6, may impair the elimination of risperidone, primarily by inhibiting CYP2D6-mediated 9-hydroxylation and to a lesser extent by simultaneously affecting the further metabolism of 9-OH-risperidone or other pathways of risperidone biotransformation. Careful clinical observation and possibly monitoring of plasma risperidone levels may be useful whenever paroxetine is co-administered with risperidone.

A Pilot Study on Risperidone Metabolism

The limited available information on plasma risperidone levels shows a stable relationship between daily doses of risperidone and total plasma concentration (risperidone plus its active metabolite 9-hydroxyrisperidone). The ratio between risperidone and 9-hydroxyrisperidone characterizes cytochrome P450 2D6 (CYP2D6) status. According to the manufacturer, the CYP2D6 genotype or drugs that influence CYP2D6 or other cytochrome P450 isoenzyme activity are not expected to be clinically significant. One case report suggests that CYP3A participates in the metabolism of risperidone. A case series of 13 risperidone patients (the initial case and 12 new cases) who were genotyped for CYP2D6 were followed, and another 20 risperidone patients from a case-control study for the CYP2D6 genotype were reviewed. The CYP2D6 poor metabolizers, who are enzyme deficient (2/13 in the case series and 3/20 in the case-control study), did not appear to tolerate risperidone well. Drugs affecting CYP3A, in particular powerful inducers and inhibitors, resulted in at least a 2-fold decrease or increase in plasma risperidone levels. The anecdotal nature of this study is clearly a limitation. Drugs influencing CYP3A and CYP2D6 metabolic activity may significantly affect risperidone levels. Thus, plasma level monitoring of risperidone in a clinical setting may be useful, especially if patients are taking multiple medications or a CYP2D6 deficiency is suspected. New prospective studies under more controlled conditions are needed to verify these hypotheses.

Pharmacokinetic-pharmacodynamic modeling of risperidone effects on electroencephalography in healthy volunteers.

CNS-active drugs produce specific electroencephalographic changes and the concentration-effect relationship of antipsychotics may be elucidated by adopting electroencephalography (EEG) as an effect measurement tool. The purpose of the present study was to determine the concentration-effect relationship of risperidone by assessing the EEG effect after oral administrations of single dose risperidone in healthy young males. Nine healthy male volunteers received a 1 mg single oral dose of risperidone according to a placebo controlled crossover design. Plasma levels of risperidone and its active metabolite 9-hydroxyrisperidone were measured by radioimmunoassay. Quantitative EEG parameters were obtained for each of four frequency bands through spectral EEG analysis. The difference in the absolute power in the delta frequency band for the F3 lead between risperidone and placebo was used as a drug effect parameter. For pharmacokinetic-pharmacodynamic modeling, the hypothetical effect compartment kinetically linked to plasma by a first-order process was postulated. All curve fittings were done with the non-linear curve-fitting program NONLIN. Our results showed that absolute powers in delta and theta frequency bands were higher for risperidone administration than for placebo at all EEG leads, and the maximum effects were detected at about 3 h after administration of the drug. The hysteresis loop was observed in the plot of plasma concentration of risperidone or sum of risperidone and 9-hydroxyrisperidone (Cp) versus EEG effect for each subject. A linear model adequately described the relationship between the effect compartment concentrations (Ce) and EEG effects, and the two limbs of hysteresis in the Cp-effect plot were collapsed in the Ce-effect plot for risperidone or risperidone plus 9-hydroxyrisperidone. The increases of absolute power for delta and theta frequency bands of EEG were induced by single oral administration of risperidone. The linear PK-PD model fit well with the relationship between effect compartment concentrations (Ce) and EEG effects of risperidone.

Distribution after repeated oral administration of different dose levels of risperidone and 9-hydroxy-risperidone in the brain and other tissues of rat.

Rats were treated with daily oral doses of 1, 4, and 6 mg/kg risperidone (RSP) and its metabolite, 9-hydroxy-risperidone (9-OH-RSP), for 15 consecutive days. Concentrations of RSP and 9-OH-RSP were measured in plasma, brain, liver, kidney, lungs and fat tissue by high-performance liquid chromatography with electrochemical detection. Non-specific distribution of RSP and 9-OH-RSP in various brain regions was also studied after administration of 6 mg/kg per day oral dose for 15 days. After RSP treatment, concentrations of 9-OH-RSP were higher than those of RSP in plasma and tissues except in brain, where both compounds were present in nearly equal concentrations. Similarly, after 9-OH-RSP treatment, levels of 9-OH-RSP were higher than levels of either RSP or 9-OH-RSP or the sum of RSP and 9-OH-RSP levels measured after treatment with RSP. There was a moderate relationship between RSP dose and tissue levels of RSP and 9-OH-RSP (all rs > or = 0.62, P < 0.01), except in fat. There was also a strong relationship between the dose and tissue levels of 9-OH-RSP (all rs > or = 0.68, P < 0.005). A significant relationship was found between plasma levels of RSP and brain levels of RSP and 9-OH-RSP (all rs > or = 0.57, P < 0.03) after treatment with RSP. After 9-OH-RSP treatment, a much stronger relationship was observed between plasma and brain 9-OH-RSP levels (rs > or = 0.90, P < 0.005). The plasma concentrations of RSP and 9-OH-RSP appear to reflect their concentrations in brain. The tissue-to-plasma ratios of RSP and 9-OH-RSP were relatively low compared to other antipsychotics. In liver, kidney and lung the tissue to plasma ratio for RSP and 9-OH-RSP after treating with RSP ranged from 0.85 to 3.4. The brain to plasma ratio for RSP and 9-OH-RSP was several-fold lower than that in peripheral tissues. After RSP administration, the mean brain to plasma level ratio for RSP was 0.22, and for 9-OH-RSP to it was 0.04. The brain to plasma ratio of 9-OH-RSP after giving 9-OH-RSP was similarly low (0.04). The low brain/plasma ratio of high potency RSP and 9-OH-RSP may in part be due to their low lipophilicity, log P = 3.04 and 2.32, respectively, resulting in limited non-specific accumulation in brain tissue.

Determination of Risperidone in Plasma by High-Performance Liquid Chromatography with Electrochemical Detection: Application to Therapeutic Drug Monitoring in Schizophrenic Patients

A highly sensitive high-performance liquid chromatography method with electrochemical detection for the determination of risperidone in plasma has been developed. Remoxipride is used as an internal standard. A simple one-step extraction with 25% methylene dlchloride In pentane is used to isolate the drug from the plasma. This is followed by high-performance liquid chromatography analysis on a cyano column with electrochemical detection. Under the experimental conditions described here, commonly coadministered drugs and other antipsychotic drugs did not interfere with the analysis of either risperidone or the internal standard. Also, the available two metabolites of risperidone did not Interfere in the assay. This method has sufficient sensitivity to quantitate risperidone accurately at 0.1 ng/mL, whenl mL of plasma was used for the analysis, with a coefficient of variation of <9%. This method has been successfully used In the determination of plasma levels of risperidone in schizophrenic patients treated with 4-, 6-, and 8-mg oral doses per day.