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Biomedical subjects

C L DeVane

Publications and source records attributed to C L DeVane.

At least 37 records · Page 2Linked to original sources
PubMed2000

Olanzapine pharmacokinetics in pediatric and adolescent inpatients with childhood-onset schizophrenia.

Well-designed studies investigating how pediatric or adolescent patients with mental disorders respond to and metabolize the newer antipsychotic drugs are practically nonexistent. Without such data, clinicians have difficulty designing appropriate dosage regimens for patients in these age groups. The results from a study of olanzapine pharmacokinetics in children and adolescents are described. Eight inpatients (ages 10-18 years) with treatment-resistant childhood-onset schizophrenia received olanzapine (2.5-20 mg/day) over 8 weeks. Blood samples, collected during dose titration and at a steady state provided pharmacokinetic data. The final evaluation (week 8) included extensive sampling for 36 hours after a 20-mg dose. Olanzapine concentrations in these eight pediatric patients were of the same magnitude as those for nonsmoking adult patients with schizophrenia but may be as much as twice the typical olanzapine concentrations in patients with schizophrenia who smoke. Olanzapine pharmacokinetic evaluation gave an apparent mean oral clearance of 9.6 +/- 2.4 L/hr and a mean elimination half-life of 37.2 +/- 5.1 hours in these young patients. The determination of the initial olanzapine dose for adolescent patients should take into consideration factors such as the patient's size. In general, however, the usual dose recommendation of 5 to 10 mg once daily with a target dose of 10 mg/day is likely a good clinical guideline for most adolescent patients on the basis of our pharmacokinetics results.

Adolescent↗
PubMed2000

Single-dose pharmacokinetics of methylphenidate in CYP2D6 extensive and poor metabolizers.

Six adults phenotyped as either extensive (N = 4) or poor (N = 2) metabolizers for cytochrome P450 (CYP) 2D6 were given a 10-mg oral dose of methylphenidate (MPH) on two separate occasions with and without quinidine, a potent CYP2D6 inhibitor. Quinidine had no significant effect on the pharmacokinetics of either MPH or ritalinic acid, its major metabolite, in either group of CYP2D6 metabolizers. These data suggest a lack of involvement of CYP2D6 in the metabolism of MPH. Drugs that are inhibitors of CYP2D6 when taken concurrently with MPH should not affect its plasma concentration.

Adolescent↗
PubMed2000

An assessment of selective serotonin reuptake inhibitor discontinuation symptoms with citalopram.

The selective serotonin reuptake inhibitors (SSRIs) have recently been associated with a variety of somatic and psychiatric symptoms upon abrupt drug discontinuation. These symptoms have been variously termed SSRI withdrawal, or SSRI discontinuation syndrome. Although all of the available SSRIs have been reported to cause discontinuation symptoms, some appear to have a greater propensity to cause these adverse events than others. Data from a previously completed placebo-controlled, double-blind study designed to assess citalopram in depression relapse prevention were analysed to assess patients for the emergence of discontinuation effects following randomization to placebo after 8 weeks of active drug treatment. Side-effects that occurred during the first 2 weeks following randomization to active drug (n = 150) or placebo (n = 72) were measured using the UKU unwanted side-effect list. The proportion of patients that experienced one or more events over the 2-week period following randomization was similar in the two groups, and there was no association between citalopram dose prior to randomization and the reporting of symptoms. Most of the events that did occur were mild in intensity and none resulted in discontinuation from the study. Events occurring at a higher frequency in the placebo group were most associated with the central nervous system (CNS). These events may reflect a re-emergence of depressive symptoms, since only 14.8% of patients randomized to placebo who did not relapse experienced CNS events, a low symptom incidence that was non-significant (P = 0.562) compared to patients continuing treatment (10.9%). Therefore, this assessment suggests that any symptoms associated with rapid discontinuation of citalopram are mild and transient, and emphasizes the significant role re-emerging depression and / or anxiety may play in the assessment and identification of SSRI discontinuation symptoms.

Citalopram↗
PubMed2000

Avoiding psychotropic drug interactions in the cardiovascular patient.

Recent advances in our understanding of the hepatic cytochrome P450 inhibitory effects of the newer antidepressants have increased concern about drug interactions in the practice of psychiatry. The authors summarize the potential interactions of psychoactive drugs with cardiovascular medications. Practicing psychiatrists encounter many patients with cardiovascular disease, and an awareness of these interactions will improve knowledgeable prescribing for medically ill patients with comorbid mental disorders.

Cardiovascular Agents↗
PubMed2000

Ethylphenidate formation in human subjects after the administration of a single dose of methylphenidate and ethanol.

Ethylphenidate was recently reported as a novel drug metabolite in two overdose fatalities where there was evidence of methylphenidate and ethanol coingestion. This study explores the pharmacokinetics of ethylphenidate relative to methylphenidate and the major metabolite ritalinic acid, in six healthy subjects who received methylphenidate and ethanol under controlled conditions. Subjects (three males, three females) received a single oral dose of methylphenidate (20 mg; two 10-mg tablets) followed by consumption of ethanol (0.6 g/kg) 30 min later. Methylphenidate, ritalinic acid, and ethylphenidate were quantified using liquid chromatography-tandem mass spectrometry. Ethylphenidate was detectable in the plasma and urine of all subjects after ethanol ingestion. The mean (+/-S.D.) area under the concentration versus time curve for ethylphenidate was 1.2 +/- 0.7 ng/ml/h, representing 2.3 +/- 1.3% that of methylphenidate (48 +/- 12 ng/ml/h). A significant correlation was observed between the area under the concentration versus time curve of methylphenidate and that of ethylphenidate. In view of the known dopaminergic activity of racemic ethylphenidate, it remains possible that under certain circumstances of higher level dosing, e.g., in the abuse of methylphenidate and ethanol, the metabolite ethylphenidate may contribute to drug effects.

Adult↗
PubMed2000

Pharmacologic characteristics of ideal antidepressants in the 21st century.

The availability of drugs for use as antidepressants has expanded greatly in the past 2 decades. Not only has the number of drugs increased but so has the diversity in associated pharmacologic effects. Drug development for central nervous system agents is proceeding at an accelerated pace. The coming decades hold the promise for the introduction of newer antidepressants that have novel mechanisms of action, improved adverse event profiles, and expanded indications. Unfortunately, the ideal antidepressant is yet to be formulated. Pharmacologic characteristics for desirable improvements are discussed relative to the currently available drugs.

Adrenergic Uptake Inhibitors↗
PubMed1999

Metabolism and pharmacokinetics of selective serotonin reuptake inhibitors.

1. Five drugs with the predominant pharmacologic effect of inhibiting the neuronal reuptake of serotonin are available worldwide for clinical use. This class of psychoactive drugs, known as selective serotonin reuptake inhibitors (SSRIs), is comprised of fluoxetine, sertraline, paroxetine, fluvoxamine, and citalopram. 2. The SSRIs appear to share similar pharmacodynamic properties which translate to efficacy in the treatment of depression and anxiety syndromes. The drugs are differentiated by their pharmacokinetic properties with regard to stereochemistry, metabolism, inhibition of cytochrome enzymes, and participation in drug-drug interactions. Studies focusing on the relationship of plasma drug concentration to therapeutic and adverse effects have not confirmed the value of plasma concentration monitoring. 3. This review summarizes the metabolism and relevant pharmacokinetic properties of the SSRIs.

Age Factors↗
PubMed1999

Drug interactions with psychostimulants.

The psychostimulants methylphenidate, dextroamphetamine, and pemoline are among the most common medications used in child and adolescent psychiatry. Often, these agents are used in combination with other medications. This review summarizes reported drug interactions and assesses both causality and clinical significance. A computerized search was undertaken using MEDLINE (1966 to 1998) to obtain all pertinent reports of adverse events associated with the coadministration of psychostimulants and other drugs. A total of 38 reports involving 25 different drugs from various classes were systematically evaluated along with research studies conducted to specifically assess drug interactions. Methylphenidate appeared to be involved primarily in pharmacokinetic interactions suggestive of cytochrome P450 inhibition while dextroamphetamine and pemoline were more often involved in apparent pharmacodynamic interactions. The published data support the safe use of psychostimulants with most classes of medications with few absolute contraindications.

Anticonvulsants↗
PubMed1999

Evaluation of the efficacy, safety and physiological effects of fluvoxamine in social phobia.

There is no US Food and Drug Administration (FDA) approved treatment for social phobia although data suggest efficacy for several drug classes, including beta-blockers, benzodiazepines, monoamine oxidase inhibitors, and selective serotonin reuptake inhibitors (SSRIs). The SSRIs are particularly attractive due to their favourable tolerance and safety profile. An open label trial of fluvoxamine was conducted to evaluate its efficacy and safety in the treatment of social phobia (DSM-III-R) and to assess physiological changes that may accompany treatment. Fifteen non-depressed patients, aged 22-44 years (mean 31.6 years), entered the study. A 5-min performance task (public speaking simulation) preceded and concluded the active treatment period. Cardiovascular monitoring was performed during this time and blood sampled for plasma cortisol and steady-state plasma fluvoxamine concentration (at week 7). Ten patients (5 men and 5 women) completed an active 6 week treatment period of flexible dosing (50-150 mg/day). Five patients failed to complete the study due to drowsiness (n = 2), nausea (n = 1), or were lost to follow-up (n = 2). Analysis of clinical ratings indicated a statistically significant decrease in all scales from baseline to week 7 at the conclusion of the active treatment period. Clinical benefits were still evident at follow-up 1 week after drug discontinuation. Neither physiological effects nor plasma drug concentration correlated with clinical change. Fluvoxamine appeared to be effective and well tolerated in completers. Randomized clinical trials are needed to further demonstrate the efficacy of fluvoxamine in the treatment of social phobia.

Adult↗
PubMed1999

Disposition of morphine in tissues of the pregnant rat and foetus following single and continuous intraperitoneal administration to the mother.

Foetal exposure to maternally administered opiates such as morphine represent a serious human health problem but disposition studies in man are difficult to perform. Morphine disposition was therefore investigated in pregnant rats and their foetuses near term as a model. Disposition was examined either following intraperitoneal dosing as a single dose or continuous infusion. A high-pressure liquid chromatography assay for morphine in plasma and tissue was developed and validated. Following the single morphine dose, foetal distribution was rapid and concentrations in foetal and placental tissue were from 2.6 (whole foetus) to 27.6 (placenta) times higher compared with maternal plasma. The rank order of the area under the concentration vs time curve (AUC) of morphine in tissues was: placenta > or = foetal liver > foetal brain > whole foetus > maternal brain. The foetal brain to maternal brain AUC ratio for morphine was 9.5, suggesting large differences in their blood-brain barrier permeability. Following continuous administration of morphine there were significant linear relationships between maternal plasma and tissue concentrations with the same rank order as the single dose study. However, following continuous administration the relative amount of morphine in placenta and foetal liver was reduced by half and one-third, respectively, compared with the single dose study. These results document why the rat foetus is particularly susceptible to the pharmacodynamic effects of morphine following maternal administration.

Analgesics, Opioid↗
PubMed1999

No mourning for the conventional antipsychotics: the dawn of the atypical agents.

As Markowitz et al. explain, the atypical antipsychotics should become the first-line agents for the treatment of schizophrenia. There is much to be learned about these drugs, but their displacement of the conventional antipsychotics will be a continuous process. The loss of the older drugs will not be mourned.

Antipsychotic Agents↗
PubMed1999

Mirtazapine in major depression with comorbid generalized anxiety disorder.

BACKGROUND: A high proportion of patients with generalized anxiety disorder (GAD) have comorbid depressive illness. The presence of anxiety in depression has significant prognostic implications. Because of mirtazapine's early anxiolytic effects, the present study was undertaken as a preliminary investigation in patients with a diagnosis of major depression with comorbid GAD. METHOD: Mirtazapine was administered to 10 patients with DSM-IV major depressive disorder and comorbid GAD in an 8-week open-label study. Mirtazapine was increased from an initial daily dose of 15 mg to a maximum daily dose of 45 mg. RESULTS: Patients were found to have significant reductions in Hamilton Rating Scale for Depression scores, Hamilton Rating Scale for Anxiety scores, and Beck Depression Inventory scores, with improvement noted after the first week of therapy and continuing improvement over the 8 weeks of study. CONCLUSION: These positive preliminary findings support the further investigation of mirtazapine's potential value as a treatment for generalized anxiety disorder in addition to its established efficacy as an antidepressant drug.

Adult↗
PubMed1999

Pharmacokinetic considerations of antidepressant use in the elderly.

The elderly can be more difficult to treat with antidepressants than are young adults. Older patients take more medications, which increases the potential for drug interactions. Their altered physiology results in widely variable plasma drug concentrations from standard doses. Pharmacokinetic and pharmacodynamic changes in this population may predispose patients to experience an increased number of adverse events. The newer antidepressants have been studied for pharmacokinetic changes in the elderly compared with younger volunteers. Most antidepressants show some changes, including slower metabolic clearance and an extended elimination half-life, although the changes described are not uniform between drugs. Recommended initial doses are lower for the elderly for all antidepressants, although optimal doses may not differ from those for younger patients once dosing is individualized.

Adult↗
PubMed1998

Bupropion slow-release response in depression: diagnosis and biochemistry.

BACKGROUND: Bupropion has been previously shown to be particularly beneficial in bipolar and atypical depression. Previous research has supported a possible association of response to plasma levels and to changes in plasma homovanillic acid (HVA). These findings were here extended to bupropion slow-release (SR), a formulation with slower release kinetics. METHODS: Forty-one patients with major depressive disorder (DSM-III-R) completed 8 weeks of a fixed dose of 300 mg/day in two doses/day. Clinical outcome measures were the Hamilton Depression Rating Scale (HDRS) and Beck Depression Inventory (BDI). Biological parameters included plasma HVA and 3-methoxy-4-hydroxyphenyl-glycol (MHPG), as well as a final measurement of plasma bupropion and its metabolites. RESULTS: Response to bupropion SR differed among the three groups: results for change in HDRS and in BDI were greater in the bipolar and atypical than in the "typical" depressed patients. Mean change in HDRS was, respectively, of 15.6, 17.1, and 7.6 (F = 5.57, p < .01); mean change in the BDI, 21.1, 16.9, and 7.3 (F = 3.32, p < .05). Threobupropion levels correlated with HDRS scores (r = .47, p = .02, n = 23); plasma HVA and MHPG increased significantly (t = 2.31, p = .03; t = 2.15, p = .04, n = 17). Bipolar depressed patients' improvement in HDRS was related to increases in MHPG (r = .87, p = .01) and in HVA (r = .70, p = .08). CONCLUSIONS: This fixed-dose study indicates that there may be specific benefits for bupropion SR in atypical and bipolar depression, and that these benefits may be related also to plasma levels and biochemical changes in catecholamines. Due to the small sample size, replication is of key importance.

Adult↗
PubMed1998

Therapeutic drug monitoring of alprazolam in adolescents with asthma.

Children and adolescents with severe asthma frequently experience anxiety or depression with anxiety, which can undermine their response to treatment. In addition, these patients often receive theophylline and a variety of adrenergic stimulants, which can exacerbate or worsen anxiety. Such children occasionally are candidates for treatment with anxiolytic therapy. There is a paucity of drug disposition data in adolescents for benzodiazepines, the most frequently used antianxiety drugs. The authors monitored the steady state alprazolam plasma concentration in six children with severe asthma who were administered standard doses of alprazolam. In one patient administered concurrent therapy with troleandomycin, a recognized cytochrome 3A4 inhibitor, alprazolam plasma concentration was markedly elevated. Overall, the disposition data of alprazolam was consistent with data previously reported in adults. Alprazolam appeared to be safe and effective for use in adolescents with asthma.

Adolescent↗
PubMed1998

Translational pharmacokinetics: current issues with newer antidepressants.

Translational pharmacokinetics involves the application of our knowledge of drug metabolism and disposition to clinical practice. The newer antidepressants are a diverse group of compounds in terms of pharmacokinetic properties and the potential for participation in drug interactions. Clinical questions have been taken into the laboratory and the results back into the clinic. Unfortunately, several issues are unresolved. The clinical significance of the stereochemistry of the newer antidepressants is poorly investigated. Several drugs produce pharmacologically active metabolites and demonstrate nonlinearity in their disposition. Plasma concentration ranges associated with therapeutic benefits have not been established to guide drug dosing in nonresponsive patients. Each of the newer antidepressants has a distinct profile of affinity for cytochrome P-450 isozymes. Even within the class of selective serotonin reuptake inhibitors (SSRIs), inhibition of P-450 isozymes differ substantially. Care must be taken when prescribing certain drug combinations to control drug interactions. Translating the pharmacokinetic differences among the newer antidepressants to clinical practice has significance for designing effective drug dosage regimens.

Antidepressive Agents↗