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Biomedical subjects

Sheldon H Preskorn

Publications and source records attributed to Sheldon H Preskorn.

At least 37 records · Page 2Linked to original sources
PubMed2005

Effect of study criteria on recruitment and generalizability of the results.

OBJECTIVE: Clinical trials are indispensable to drug approval process. This research examined the effect of a specific study criteria on recruitment and generalizability of the results. METHODS: The following were reviewed: (a) the usual inclusion and exclusion criteria for the antipsychotic trials performed at the Institute; (b) epidemiologic data, to determine the effect of study criteria on the target population; and (c) the recruitment procedures/strategies used to identify potential candidates. A survey was conducted to determine the percentage of schizophrenic patients in a conventional outpatient psychiatric clinic conforming to the usual enrollment criteria for antipsychotic trials. RESULTS: Intensive recruitment efforts in a general population of 3.6 million would have been expected to yield only 632 eligible subjects out of 36,000 suffering from schizophrenia. Out of 632, only 50 contacted the research site after an intensive recruitment effort. From those 50, 30 were excluded during a telephone interview. Of the 20 remaining, 6 were excluded for a variety of reasons during a face-to-face interview. Thus, only 14 subjects out of a population of 3.6 million met the study criteria. CONCLUSIONS: These results emphasize the rarified nature of patients-volunteers who enter a clinical trial. Inclusion and exclusion study criteria can severely restrict the number of eligible subjects, dictate recruitment strategies, and in turn affect generalizability of the results.

Clinical Trials as Topic↗
PubMed2005

Pharmacokinetics and therapeutics of acute intramuscular ziprasidone.

Patients with acute psychosis often exhibit agitation, which can be distressing and hazardous to others as well as to the patient. In such psychiatric emergencies, intramuscular antipsychotic agents can be easier to administer than oral formulations, and they have the added advantage of more rapid absorption and a faster onset of action. However, intramuscular formulations of conventional antipsychotics, which have been the standard treatment, are associated with acute dystonia and other movement disorder-related adverse events. Ziprasidone is the first atypical antipsychotic to be clinically available in both intramuscular and oral formulations in the US. The intramuscular formulation of ziprasidone, ziprasidone mesylate, uses sulfobutylether beta-cyclodextrin to solubilise the drug by complexation. The pharmacokinetics of intramuscular ziprasidone include rapid attainment of therapeutic drug level (time to reach peak serum concentration [tmax]<or=60 minutes postdose), a mean terminal elimination half-life ranging from 2 to 5 hours, bioavailability of approximately 100%, exposure to drug that increases in a dose-related manner and little drug accumulation even after 3 days of repeated intramuscular administration. The metabolism and elimination of intramuscular ziprasidone have not been extensively evaluated. The principal difference between any oral versus intramuscular formulations of a drug is in first-pass metabolism. Oral ziprasidone is eliminated mainly via the hepatic route and <1% is eliminated in urine and <4% in faeces as unchanged drug. That would not be expected to change with the intramuscular route of administration. Low concentrations of ziprasidone are seen 12-18 hours after the last intramuscular injection. The rapid clearance of ziprasidone from plasma after an intramuscular administration results in little to no persistence of plasma drug level when switching from intramuscular to oral drug administration. No clinically significant age-, sex- or race-related effects on the pharmacokinetics of intramuscular or oral ziprasidone have been noted, and the tolerability and cardiovascular safety profiles of intramuscular ziprasidone have been well characterised in clinical trials.

Antipsychotic Agents↗
PubMed2004

Demonstration of the efficacy and safety of a novel substance P (NK1) receptor antagonist in major depression.

The efficacy and safety of a selective NK(1) antagonist, L-759274, was investigated in outpatients with diagnosis of major depressive disorder with melancholic features, following evidence obtained with the novel compound aprepitant that Substance P (NK(1)) antagonists may provide a unique mechanism of antidepressant activity. A randomized, double-blind placebo-controlled study was carried out. Patients, male or female, aged 18-60, scoring >/=25 points on total of first 17 items of 21-item Hamilton Depression Scale (HAMD), and scoring >/=4 (moderately ill) on Clinical Global Impressions-Severity Scale were randomized to oral L-759274 40 mg daily (n=66) or placebo (n=62) for 6 weeks. For patients receiving L-759274, improvement (mean decrease from baseline) in HAMD-17 total score was 10.7 points, compared with a mean 7.8 point improvement in patients receiving placebo (p<0.009). Mean scores for item 1 of HAMD-17 (depressed mood) also improved to a greater extent in the active group compared with the placebo group (0.3 points, p<0.058). Compared with placebo, mean scores on Clinical Global Impressions-Improvement Scale improved significantly by the end of the trial (p=0.009). L-759274 was generally safe and well-tolerated. The incidence of sexual side effects was on par with that observed in patients receiving placebo, and the incidences of gastrointestinal effects were low. Antidepressant actions have now been observed with two different highly selective NK(1) antagonists (aprepitant and L-759274). NK(1) antagonism is a replicated and generally well-tolerated antidepressant mechanism.

Adolescent↗
PubMed2004

Duloxetine.

Explore the source record for details and available documents.

Antidepressive Agents↗
PubMed2004

Concurrent administration of donepezil HCl and risperidone in patients with schizophrenia: assessment of pharmacokinetic changes and safety following multiple oral doses.

AIM: This open-label, multiple-dose trial investigated the effect of concurrent administration of donepezil HCl with risperidone on the pharmacokinetics (PK) and safety profiles of both drugs. METHODS: Sixteen male patients with schizophrenia, who were receiving stable, physician-optimized risperidone (1-4 mg twice daily), and 15 healthy age- and weight-matched male controls, received donepezil HCl 5 mg daily for 7 days. Patients with schizophrenia remained on their physician-optimized dose of risperidone throughout the study. Pharmacokinetic parameters (C(max), t(max) and AUC) were assessed from plasma drug concentrations measured in blood collected before, during and after administration (for 12 h after risperidone on days 0 and 7, and for 24 h after donepezil HCl on day 7). RESULTS: The mean age of all the subjects was 38.5 years. Donepezil PK parameters were similar between patients taking donepezil HCl + risperidone (AUC(0-24 h) = 329.0 +/- 17.2 ng x h ml(-1)) and controls taking donepezil HCl alone (AUC(0-24 h) = 354.7 +/- 28.2 ng x h ml(-1)). Pharmacokinetic parameters for risperidone and 9-OH risperidone were not altered in patients with schizophrenia after 7 days of donepezil HCl administration (AUC(0-12 h) standardized by dose: risperidone = 59.6 +/- 16.3 ng.h ml(-1) at day 0, 56.0 +/- 15.8 ng x h ml(-1) at day 7; 9-OH risperidone = 162.1 +/- 19.2 ng x h ml(-1) at day 0, 163.3 +/- 15.0 ng x h ml(-1) at day 7). The most common adverse event in both treatment groups was diarrhoea (6/16 risperidone + donepezil HCl patients and 9/16 donepezil HCl only subjects). There were no significant changes in physical examination, ECG, vital signs or treatment-emergent abnormal laboratory values associated with either of the treatment regimens. No subject developed extrapyramidal side-effects following donepezil administration. CONCLUSIONS: These results suggest that once-daily dosing of 5 mg donepezil HCl does not alter the PK of risperidone in patients with schizophrenia. The combination of risperidone and donepezil HCl was well tolerated.

Administration, Oral↗
PubMed2004

Intramuscular haloperidol or lorazepam and QT intervals in schizophrenia.

The objective of this study was to estimate the effects of intramuscular haloperidol and lorazepam on the QT interval in volunteers with schizophrenia. Intramuscular haloperidol and intramuscular lorazepam are standard treatments in the acute management of agitation and aggression. Although prolongation of the QT interval and sequelae, including torsade de pointes and death, have been reported for haloperidol (but not lorazepam), formal studies have been lacking. Volunteers with schizophrenia (n = 12) were administered a single intramuscular injection of 7.5 mg haloperidol or 4 mg lorazepam in a blinded, randomized, placebo-controlled crossover design. Serial EKGs and concurrent blood samples were obtained over 6 hours following each injection. Changes in the QT interval were evaluated, as were plasma drug and prolactin concentrations. Haloperidol injection increased the heart rate-corrected QT interval an average of 5.1 msec using Bazett's correction (QTb 90% confidence interval [CI]: 0.3, 9.8), 3.6 msec using Fridericia's correction (QTf 90% CI: 0.02, 7.2), and 4.2 msec using an empirically derived "baseline correction" (QT(ii) 90% CI: 0.3, 8.0). Effects of lorazepam on QT were nullified by correction for the heart rate elevation (QTb 3.8 msec, 90% CI: 0.6, 7.1; QTf 0.0 msec, 90% CI: -3.2, 3.4; QTii -2.3 msec, 90% CI: -6.6, 2.0). An association between QT prolongation and occurrence of extrapyramidal symptoms was observed. On average, intramuscular haloperidol led to minimal prolongation of the QT interval. This propensity is of theoretical concern in individuals with risk factors for torsade de pointes but seems unlikely to be a problem in the vast majority of patients.

Adult↗
PubMed2004

How drug-drug interactions can impact managed care.

DDIs have important implications for managed care. They can adversely impact patient outcomes and can also have serious cost implications. The problem posed by unintended and adverse DDIs will continue to grow in importance as the complexity and uniqueness of medication regimens escalate in an aging population using increasingly sophisticated and varied pharmacological agents. In this paper, antidepressants and SSRIs in particular were used to illustrate these important points.

Antidepressive Agents↗