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C L DeVane

Publications and source records attributed to C L DeVane.

At least 55 records · Page 3Linked to original sources
PubMed1998

Differential pharmacology of newer antidepressants.

New antidepressants have become available for clinical use in the 1990s. Before this decade, the drugs available to treat depression consisted essentially of lithium, the monoamine oxidase inhibitors, and tricyclic antidepressants. Trazodone and bupropion, introduced in the mid-1980s, were the first major departures from the pharmacology of the tricyclics. Following the introduction in 1988 of the first serotonin selective reuptake inhibitor (SSRI) in the United States, the options have expanded and now include four SSRIs (fluoxetine, sertraline, paroxetine, fluvoxamine), nefazodone, venlafaxine, and mirtazapine. Citalopram and reboxetine are expected to be available by the end of the decade. These newer drugs possess a variety of pharmacological characteristics that are relevant to the choice of an antidepressant for clinical use. This review summarizes some of the major pharmacokinetic and pharmacodynamic similarities and differences among these drugs.

Absorption↗
PubMed1997

Extrapyramidal symptoms associated with cyclic antidepressant treatment: a review of the literature and consolidating hypotheses.

Extrapyramidal symptoms (EPS) including parkinsonism, akathisia, dystonia, and tardive dyskinesia have commonly been associated with acute or chronic administration of neuroleptic drugs. A review of the medical literature reveals a substantial number of cases with similar clinical characteristics associated with the tricyclic antidepressants, monoamine oxidase inhibitors, and selective serotonin reuptake inhibitors (SSRIs). Although the data are not sufficient to make definitive pharmacoepidemiologic conclusions, the available number of case reports suggests the SSRIs may be more common offenders in producing these adverse drug effects. The exact mechanism is elusive but likely involves complex interactions of dopamine, serotonin, and norepinephrine between cortical structures and the basal ganglia. The final common pathway for production of EPS seems to be indirect modulation of dopaminergic function. Predictors of patients at risk for antidepressant-induced EPS are not established, but a greater awareness of the potential for these drug side effects to occur may increase their recognition and decrease antidepressant-induced morbidity.

Antidepressive Agents, Second-Generation↗
PubMed1997

Clinical pharmacokinetics of fluvoxamine: applications to dosage regimen design.

BACKGROUND: The disposition characteristics and pharmacokinetic parameters of drugs provide fundamental data for designing safe and effective dosage regimens. A drug's volume of distribution, clearance, and the derived parameter, half-life, are particularly important, as they determine the degree of fluctuation between a maximum and minimum plasma concentration during a dosage interval, the magnitude of the steady-state concentration, and the time to reach a steady-state plasma concentration upon chronic dosing. Potential drug-drug interactions can be predicted with knowledge of affinities for various cytochrome P450 (CYP) isozymes. METHOD: The literature was searched for information related to the pharmacokinetic properties of fluvoxamine and reports of its involvement in drug interactions. RESULTS: The primary pharmacokinetic variables for fluvoxamine have been estimated in single and multiple dose studies in animals, health volunteers, and patients. Fluvoxamine is well absorbed after oral administration, widely distributed in the body, and eliminated with a mean half-life of 15 hours and a range from 9 hours to 28 hours. Its disposition is altered in hepatic, but not renal, disease. Data from elderly subjects reflect a modest need for dosage adjustment in this population. Fluvoxamine produces no active metabolites. The specific cytochrome isozymes involved in the hepatic elimination of the drug are undefined. Data from studies relating the plasma concentration of fluvoxamine to its clinical effects do not support routine plasma concentration monitoring in depression or anxiety disorders. Fluvoxamine has prominent affinity for the CYP12 isozyme, lesser affinity for the CYP3A4 and CYP2C isozymes, and minimal affinity for CYP2D6. This profile suggests the need for careful dosage adjustment when used together with some drugs that have a narrow therapeutic range in order to minimize inhibiting their metabolism. CONCLUSION: Overall, the pharmacokinetic profile of fluvoxamine is adequately defined to provide guidelines for developing safe and effective dosage regimens for most types of patients.

Adolescent↗
PubMed1996

Pharmacokinetics of clozapine and risperidone: a review of recent literature.

The current literature describing the pharmacokinetics of the atypical antipsychotics clozapine and risperidone is reviewed, and discussion on the clinical significance of these data is presented. These drugs are well absorbed when taken orally but are poorly bioavailable because of presystemic elimination. They are highly cleared by hepatic metabolism involving specific P450 isozymes. Risperidone elimination produces a potent active metabolite. Neither of the drugs has received extensive study related to drug-drug interactions, but several are potentially important because a purported therapeutic plasma concentration range is proposed for clozapine and a possible curvilinear dose response relationship has been reported for risperidone. The current clinical pharmacokinetic database for these atypical antipsychotics suggests that much can be learned with additional study that would be of value in individualizing their dosage regimens.

Antipsychotic Agents↗
PubMed1996

Newer antidepressants and the cytochrome P450 system.

OBJECTIVE: This review evaluates the in vitro and in vivo evidence for inhibition of cytochrome P450 enzymes by the newer antidepressants and provides clinical recommendations for avoiding and managing drug interactions. METHOD: The international literature on the cytochrome P450 system and related drug interactions from 1966 to 1995 was reviewed. In vitro studies, pharmacokinetic trials in human subjects, and case reports were assessed. RESULTS: The newer antidepressants each inhibit a different cluster of cytochrome P450 enzymes, which are of relevance to the potential for drug interactions. Cytochrome P450 1A2 is inhibited by fluvoxamine and is implicated in drug interactions with theophylline, clozapine, and others. Fluoxetine, norfluoxetine, sertraline, and paroxetine are potent in vitro inhibitors of cytochrome P450 2D6 and are capable of causing marked elevations in plasma desipramine and nortriptyline concentrations. Fluoxetine, sertraline, and fluvoxamine are believed to inhibit cytochrome P450 2C because of observed interactions with phenytoin, diazepam, and other drugs metabolized by these enzymes. Cytochrome P450 3A4 metabolizes terfenadine, astemizole, carbamazepine, alprazolam, triazolam, and other benzodiazepines. Plasma concentrations of these drugs have increased when they are administered with fluvoxamine, nefazodone, fluoxetine, and sertraline. CONCLUSIONS: The majority of the newer antidepressants are associated with a risk for clinically significant drug interactions. A rapidly growing body of literature provides evidence for a distinct profile of cytochrome P450 inhibition and drug interaction risks by individual antidepressants. These findings underscore the need for definitive in vivo interaction studies of plasma from phenotyped patients treated with clinically effective antidepressant doses of medication, for direct comparative clinical studies, and for studies assessing the utility of phenotyping in clinical practice.

Antidepressive Agents↗
PubMed1996

Alopecia and mood stabilizer therapy.

Alopecia is a common side effect in patients managed on the mood stabilizers lithium, valproate, and carbamazepine. Clinicians may be reluctant to discontinue medications in patients suffering from hair loss if the mood stabilizer is otherwise efficacious. Therefore it is important to be familiar with the epidemiology, diagnosis, and management of alopecia. A single representative case is provided to illustrate briefly the common presentation of a patient with mood stabilizer-induced alopecia. A literature search was conducted to provide the basis for discussion of diagnosis, the association of mood stabilizers with alopecia, and some management options of this side effect. The diagnosis of alopecia requires an understanding of normal hair growth and is best made following a careful history, an examination, and the maintenance of a high level of suspicion. Alopecia occurs in about 10% of persons managed on lithium, up to 12% of persons on valproate, and less than 6% of individuals on carbamazepine. Management of alopecia includes reassurance, hair care techniques, trace mineral supplementation, treatment with minoxidil, and hair replacement pieces. Alopecia due to mood stabilizer drugs can be potentially identified and managed without medication discontinuation.

Adult↗
PubMed1996

The practical use of carbon dioxide-induced anxiety in the diagnosis and care of patients with panic disorder.

The authors utilized inhalation of 35% carbon dioxide and 65% oxygen as a diagnostic tool in the evaluation of suspected panic disorder. In two inpatients admitted for a medical evaluation for pheochromocytoma and carcinoid syndrome, respectively, a positive response to the double-blind administration of CO2/O2 or room air was consistent with a diagnosis of panic disorder by psychiatric history. In two additional patients in whom denial of mental illness was a psychological impediment to proper treatment, a positive CO2/O2 challenge resulted in therapeutic benefit.

Administration, Inhalation↗
PubMed1996

Serotonin selective reuptake inhibitors in child and adolescent psychopharmacology: a review of published experience.

BACKGROUND: This review summarizes the published clinical experience with the serotonin selective reuptake inhibitors (SSRIs) in children and adolescents. METHOD: A computerized literature search was conducted using MEDLINE back to 1986 to retrieve all reports of SSRI use in children and adolescents. Additional hand searches were performed with key journals. All reports relating clinical experience of SSRIs in children or adolescents were collated according to primary diagnosis. RESULTS: We found 3 double-blind, placebo-controlled clinical trials (65 patients), 16 open- label trials (322 Patients), and 23 case reports (41 patients) on the use of SSRIs in younger populations. The reports described clinical effects, mostly benefits, for 13 indications. A theoretical rationale exists for use of SSRIs in most conditions for which they are prescribed. CONCLUSION: The most convincing evidence for efficacy for SSRIs in adolescents exists for treatment of depression and obsessive-compulsive disorder. Only sparse evidence, mostly anecdotal, exists for efficacy in other conditions. The reported side effects were modest, but behavioral disturbances in some cases limit recommendations and warrant caution for widespread use.

Adolescent↗
PubMed1995

Brief comparison of the pharmacokinetics and pharmacodynamics of the traditional and newer antipsychotic drugs.

The pharmacokinetics and pharmacodynamics of chlorpromazine, haloperidol, clozapine, and risperidone are described. Most traditional antipsychotic drugs have similar pharmacokinetic profiles that differ from the newer agents in several key respects. Traditional agents tend to be completely absorbed and undergo extensive presystemic elimination, but clearance tends to be almost exclusively by hepatic-enzyme metabolism. The volume of distribution is large, steady-state plasma concentrations are highly variable, and many traditional antipsychotic drugs have pharmacologically active metabolites. The newer antipsychotic agents clozapine and risperidone are also well absorbed and undergo extensive presystemic elimination. They are cleared mostly through hepatic-enzyme metabolism, but a small portion of risperidone is cleared renally. Steady-state plasma concentrations of clozapine and risperidone exhibit large interpatient differences at therapeutic dosages. The primary metabolite of risperidone, 9-hydroxyrisperidone, has activity equipotent to that of the parent drug. It is not clear whether clozapine produces active metabolites. Basic information on the pharmacokinetics and pharmacodynamics of clozapine and risperidone is known; however, more information is needed.

Antipsychotic Agents↗
PubMed1995

Pharmacokinetics of single- and multiple-dose bupropion in elderly patients with depression.

A study of a dopaminergic antidepressant that may have an advantageous profile for use in elderly patients, bupropion, was conducted to determine the pharmacokinetics of bupropion in the elderly. Pharmacokinetics of single- and multiple-dose bupropion were examined in six elderly patients (five women and one man) diagnosed with depression. Mean (+/- SD) CL app of bupropion was 1.6 +/- 0.4 L/hr/kg, approximately 80% of the corresponding value reported for younger patients. Mean bupropion t1/2 was 34.2 +/- 8.7 hours, and average apparent Vd (Vd app) was 79.3 +/- 29.4 L/kg. Apparent half-lives (t1/2 app) of the metabolites hydroxybupropion, erythrobupropion, and threohydrobupropion were 34.2 +/- 4.6 hours, 61.4 +/- 21.6 hours, and 38.8 +/- 7.6 hours, respectively. After multiple dosing, the mean t1/2 for bupropion and its metabolites did not change significantly, although in some patients the t1/2 app of the metabolites was substantially prolonged. There was also evidence of inordinate accumulation of metabolites. The elderly are at risk for accumulation of bupropion and its metabolites. Specification of therapeutic drug monitoring parameters for bupropion treatment of the elderly is needed.

Administration, Oral↗
PubMed1994

Pharmacokinetics of the newer antidepressants: clinical relevance.

The newer antidepressants are a diverse group of compounds with distinct pharmacokinetic properties. The selective serotonin reuptake inhibitors (SSRIs)--paroxetine, sertraline, and fluvoxamine--have elimination half-lives of 15-26 hours. The extended half-life of fluoxetine (4-6 days) and its active metabolite, norfluoxetine (4-16 days), results in an extended time to steady-state and a prolonged washout period when dosing is discontinued. The SSRIs are administered as a single daily dose. Venlafaxine and nefazodone have short half-lives, 2-5 hours, and are dosed > or = 2 times daily. The newer antidepressants are all highly cleared from the body through hepatic metabolism. The biotransformation of all the drugs except paroxetine and fluvoxamine results in the formation of pharmacologically active metabolites. The newer antidepressants display a broad variability similar to the tricyclic antidepressants (TCAs) in steady-state drug concentrations. Due largely to a safer toxicity profile, the variability in clearance is of lesser importance with the newer antidepressants than with the TCAs. No useable concentration versus therapeutic effect relationship has been found with the newer drugs, and widely varying concentrations appear to have little relationship to adverse effects. Knowledge of kinetic characteristics is important for designing dosage regimens and avoiding potentially serious drug-drug interactions that are mediated through inhibition of specific hepatic cytochrome P450 enzyme pathways. Each of the SSRIs inhibits at least one cytochrome P450 enzyme, and all of the SSRIs increase serum concentrations of concomitantly administered TCAs.

Antidepressive Agents↗
PubMed1994

Pharmacogenetics and drug metabolism of newer antidepressant agents.

A wide variety of drugs are metabolized by the human cytochrome P450 system, including antidepressants such as tricyclic antidepressants and serotonin selective reuptake inhibitors (SSRIs). Each P450 isoenzyme is the product of a separate gene; a number of genes have multiple alleles that result in genetic polymorphism in the population. Both CYP2D6 and CYP2C gene families are polymorphic; both families are important in antidepressant metabolism. A number of polymorphisms result in dysfunctional or inactive enzymes. The clinical importance is highly dependent upon the patient's clinical state, coadministered drugs, therapeutic index, and the relative importance of the defective pathway in the total process of drug elimination. In addition, a number of drugs can also act as P450 enzyme inhibitors, which have the potential of causing drug interactions. In patient management, it is important to consider the fact that most antidepressants can also act as enzyme inhibitors. A number of adverse reactions resulting from coadministration of tricyclic antidepressants and SSRIs have been described. Such drug interactions can be minimized or avoided by following simple clinical logic.

Alleles↗
PubMed1994

Fetoplacental growth and placental protein synthesis in rats after chronic maternal cocaine administration.

This study evaluated the effects of chronic exposure to cocaine during pregnancy on the morphology and function of the placenta. Pregnant rats received either 45 or 60 mg/kg of cocaine hydrochloride by i.p. injection as a divided daily dose on days 8 to 18 of gestation. The maternal weight gain decreased by 20% to 24% (P < .05) in the two cocaine treatment groups, whereas the placental weight was not significantly altered. Fetal growth showed a dose-related decrease in the 45- and 60-mg/kg cocaine treatment groups; fetal body weights and length were significantly decreased by 5% to 10%. The plasma levels of cocaine were 0.79 and 1.09 micrograms/ml in the 45- and 60-mg treatment dose groups, respectively; the level in the fetal plasma was 3-fold higher in the latter group. Placental tissue explants were cultured in the presence of [35S]-methionine to investigate whether cocaine exposure altered placental protein synthesis. Secreted proteins were analyzed by polyacrylamide gel electrophoresis followed by fluorography or by western blotting and immunostaining with antibodies to placental prolactin-like proteins-B and -C and growth hormone-related protein-1. The data showed that there were no quantitative or qualitative changes in placental peptide hormone secretion as a result of the cocaine treatment. These data indicate that chronic cocaine exposure in the pregnant rat is associated with fetal growth retardation in the absence of alterations in placental morphology or secretory protein synthesis.

Amino Acid Sequence↗
PubMed1993

Evaluation of population pharmacokinetics in therapeutic trials. IV. Application to postmarketing surveillance.

The feasibility of incorporating blood sampling for population pharmacokinetic analysis into postmarketing surveillance was evaluated. Demographic and drug disposition data, consisting of two blood samples collected at a random time during two different dose intervals, was prospectively collected for 94 psychiatric inpatients (mean age, 48 +/- 13 years) receiving alprazolam. Mixed-effect modeling was used to estimate population pharmacokinetic parameters. The mean alprazolam clearance, volume of distribution, and absorption rate constant were 0.05 L/hr/kg, 0.7 L/kg, and 1.1 hr-1, respectively. Clearance was increased by 59% in women, decreased by 26% in patients with multiple organ disease, and decreased by 23% in patients older than 60 years of age. These estimates are similar to those determined from rigorous premarketing clinical trials. Interindividual variability in alprazolam clearance was relatively small (40%) after adjustment for significant patient covariates. Population pharmacokinetic analysis represents a reasonable approach to assessment of pharmacokinetic variability in a large, heterogenous patient population.

Adult↗