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Larry Ereshefsky

Publications and source records attributed to Larry Ereshefsky.

7 recordsLinked to original sources
PubMed2005

Pharmacokinetic profile and clinical efficacy of long-acting risperidone: potential benefits of combining an atypical antipsychotic and a new delivery system.

Continuous long-term antipsychotic therapy is required for patients with schizophrenia to optimise treatment benefits. The use of long-acting antipsychotic preparations can help to ensure compliance with therapy and has been shown to improve efficacy in relapse prevention when compared with oral agents. How- ever, the use of long-acting agents has been limited, since this approach to patient care has only been available with conventional drugs. The atypical antipsychotic agents have provided a new option for the treatment of schizophrenia. However, entwined with health system limitations, partial or non-compliance remains a problem with oral atypical antipsychotic agents. Combining the attributes of the atypical antipsychotic class with the pharmacokinetic profile and compliance advantages of a long-acting formulation could potentially be an important advance in the management of patients requiring continuous anti- psychotic therapy. This review considers the available clinical data supporting possible advantages for the only long-acting atypical agent currently available, long-acting risperidone, as a microsphere formulation. The drug-delivery technology employed provides a sustained therapeutic plasma level, with administration once every 2 weeks, and this is translated into improved symptom control and improved quality of life, even in patients already deemed clinically stable on an oral agent or on a conventional depot antipsychotic.

Antipsychotic Agents↗
PubMed2004

The Texas Medication Algorithm Project antipsychotic algorithm for schizophrenia: 2003 update.

BACKGROUND: The Texas Medication Algorithm Project (TMAP) has been a public-academic collaboration in which guidelines for medication treatment of schizophrenia, bipolar disorder, and major depressive disorder were used in selected public outpatient clinics in Texas. Subsequently, these algorithms were implemented throughout Texas and are being used in other states. Guidelines require updating when significant new evidence emerges; the antipsychotic algorithm for schizophrenia was last updated in 1999. This article reports the recommendations developed in 2002 and 2003 by a group of experts, clinicians, and administrators. METHOD: A conference in January 2002 began the update process. Before the conference, experts in the pharmacologic treatment of schizophrenia, clinicians, and administrators reviewed literature topics and prepared presentations. Topics included ziprasidone's inclusion in the algorithm, the number of antipsychotics tried before clozapine, and the role of first generation antipsychotics. Data were rated according to Agency for Healthcare Research and Quality criteria. After discussing the presentations, conference attendees arrived at consensus recommendations. Consideration of aripiprazole's inclusion was subsequently handled by electronic communications. RESULTS: The antipsychotic algorithm for schizophrenia was updated to include ziprasidone and aripiprazole among the first-line agents. Relative to the prior algorithm, the number of stages before clozapine was reduced. First generation antipsychotics were included but not as first-line choices. For patients refusing or not responding to clozapine and clozapine augmentation, preference was given to trying monotherapy with another antipsychotic before resorting to antipsychotic combinations. CONCLUSION: Consensus on algorithm revisions was achieved, but only further well-controlled research will answer many key questions about sequence and type of medication treatments of schizophrenia.

Algorithms↗
PubMed2003

Pharmacokinetic and pharmacodynamic interactions of oral midazolam with ketoconazole, fluoxetine, fluvoxamine, and nefazodone.

The objective of this study was to investigate pharmacokinetic and pharmacodynamic interactions between midazolam and fluoxetine, fluvoxamine, nefazodone, and ketoconazole. Forty healthy subjects were randomized to receive one of the four study drugs for 12 days in a parallel study design: fluoxetine 60 mg per day for 5 days, followed by 20 mg per day for 7 days; fluvoxamine titrated to a daily dose of 200 mg; nefazodone titrated to a daily dose of 400 mg; or ketoconazole 200 mg per day. All 40 subjects received oral midazolam solution before and after the 12-day study drug regimen. Blood samples for determination of midazolam concentrations were drawn for 24 hours after each midazolam dose and used for the calculation of pharmacokinetic parameters. The effects of the study drugs on midazolam pharmacodynamics were assessed using the symbol digit modalities test (SDMT). The mean area under the curve (AUC) for midazolam was increased 771.9% by ketoconazole and 444.0% by nefazodone administration. However, there was no significant change in midazolam AUC as a result of fluoxetine (13.4% decrease) and a statistical trend for fluvoxamine (66.1% increase) administration. Pharmacodynamic data are consistent with pharmacokinetic data indicating that nefazodone and ketoconazole resulted in significant increases in midazolam-related cognition impairment. The significant impairment in subjects' cognitive function reflects the changes in midazolam clearance after treatment with ketoconazole and nefazodone. These results suggest that caution with the use of midazolam is warranted with potent CYP3A4 inhibitors.

Administration, Oral↗
PubMed2003

Comparison of the effects of different routes of antipsychotic administration on pharmacokinetics and pharmacodynamics.

Clinicians face a dilemma when choosing between short-acting atypical antipsychotics and long-acting conventional antipsychotics. Atypical antipsychotics offer better safety and efficacy, while depot formulations of conventional antipsychotics provide more reliable drug delivery, reduced differences in peak and trough plasma levels of drug, and greater dosing precision. Risperidone was recently approved by the U.S. Food and Drug Administration as the first atypical long-acting antipsychotic medication, given as biweekly gluteal injections. This long-acting formulation is synthesized using a microsphere encapsulation process, and gradual hydrolysis of the copolymer encapsulating the drug provides a steady release of medication. Consistent with other long-acting medications, plasma drug level fluctuation is reduced more with long-acting than with oral risperidone. Analyses are currently underway to further examine safety outcomes with long-acting risperidone.

Administration, Oral↗
PubMed2002

CYP2D6 inhibition by selective serotonin reuptake inhibitors: analysis of achievable steady-state plasma concentrations and the effect of ultrarapid metabolism at CYP2D6.

STUDY OBJECTIVE: To assess the correlation between plasma concentrations of four commonly administered selective serotonin reuptake inhibitors (SSRIs) and the magnitude of cytochrome P450 (CYP) 2D6 inhibition. DESIGN: Prospective analysis. SETTING: University-affiliated research laboratory. PATIENTS: Thirty-two healthy, drug-free volunteers. INTERVENTION: Subjects were randomized to four groups and received daily administration of either fluoxetine 60 mg (as a loading dose), fluvoxamine 100 mg, paroxetine 20 mg, or sertraline 100 mg for 8 days. MEASUREMENTS AND MAIN RESULTS: The urinary concentration ratio of dextromethorphan:dextrorphan (interpreted as an in vivo index of CYP2D6 activity) was determined for each subject before and after the 8 days of receiving SSRIs. Plasma SSRI trough concentrations were measured on days 6-9. The CYP2D6 genotype was determined in a subject with an undetectable paroxetine concentration. Inhibition of CYP2D6 correlated significantly with plasma concentrations of paroxetine and fluoxetine. In contrast, no significant correlations emerged between CYP2D6 inhibition and plasma concentrations of sertraline or fluvoxamine. The subject with an undetectable paroxetine concentration was found to carry at least three functional CYP2D6 genes. CONCLUSIONS: For paroxetine and fluoxetine, plasma concentrations and dosage strongly influence the magnitude of enzyme inhibition. The potential of paroxetine (a CYP2D6 substrate) as an inhibitor may be affected by the genotypes and metabolic capacities of individual subjects.

Cyclooxygenase Inhibitors↗