Clomipramine and Exposure for Compulsive Rituals: II. Plasma Levels, Side Effects and Outcome

1980 ◽  
Vol 136 (2) ◽  
pp. 161-166 ◽  
Author(s):  
R. S. Stern ◽  
I. M. Marks ◽  
D. Mawson ◽  
D. K. Luscombe
Keyword(s):  
Side Effects ◽  
Plasma Levels ◽  
Plasma Concentrations ◽  
Therapeutic Window ◽  
Obsessive Compulsive ◽  
Behavioural Treatment ◽  
Primary Metabolite ◽  
Exposure In Vivo

SummaryForty obsessive-compulsive ritualizers received nightly placebo or clomipramine up to 225 mgs nocte for 8 months, and received behavioural treatment (exposure in vivo) from weeks 4 to 10. Plasma concentrations of clomipramine and its primary metabolite N-desmethylclomipramine steadily increased over the first 4 weeks of treatment after which they remained relatively steady. Plasma levels correlated significantly with dose and with outcome but not with side effects. Patients with plasma clomipramine levels in the range 100–250 ng/ml and N-desmethylclomipramine levels between 230–550 ng/ml were found to improve significantly more than patients outside these ranges, thus suggesting a therapeutic window for clomipramine and its primary metabolite.

Ibuprofen: Plasma Concentrations in Man

1985 ◽  
Vol 13 (1) ◽  
pp. 68-73 ◽  
Author(s):  
G M E Janssen ◽  
J F Venema
Keyword(s):  
Side Effects ◽  
Crossover Study ◽  
Plasma Levels ◽  
Healthy Subjects ◽  
Peak Plasma ◽  
Plasma Concentrations ◽  
Repeated Dose ◽  
Similar Range ◽  
The Mean ◽  
Peak Value

The plasma levels of Ibuprofen were measured in five healthy subjects who took 600 mg tablets of Ibuprofen twice daily, three times daily and four times daily in a crossover study. Peak plasma levels were obtained 1 hour after the first dose in all but one subject (slow absorber), the mean peak value being 51·3 μg.ml−1 (range 39·4–63·7 μg.ml−1). After the repeated dose regimens of two, three or four times daily of ibuprofen, the peak levels achieved were in a similar range to those seen after the first dose: Twice daily 39·4–66·4 μg.ml−1 Three times daily 43·6–63·3 μg.ml−1 Four times daily 44·1–58·4 μg.ml−1 There was no evidence of accumulation of the drug and no side-effects occurred during the trial.

scholarly journals Chemical and biological assessment of metal organic frameworks (MOFs) in pulmonary cells and in an acute in vivo model: relevance to pulmonary arterial hypertension therapy

2017 ◽  
Vol 7 (3) ◽  
pp. 643-653 ◽  
Author(s):  
Nura A. Mohamed ◽  
Robert P. Davies ◽  
Paul D. Lickiss ◽  
Blerina Ahmetaj-Shala ◽  
Daniel M. Reed ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Pulmonary Arterial Hypertension ◽  
Side Effects ◽  
Arterial Hypertension ◽  
Therapeutic Window ◽  
Endothelin 1 ◽  
Wide Range ◽  
Metal Organic ◽  
Pulmonary Arterial

Pulmonary arterial hypertension (PAH) is a progressive and debilitating condition. Despite promoting vasodilation, current drugs have a therapeutic window within which they are limited by systemic side effects. Nanomedicine uses nanoparticles to improve drug delivery and/or reduce side effects. We hypothesize that this approach could be used to deliver PAH drugs avoiding the systemic circulation. Here we report the use of iron metal organic framework (MOF) MIL-89 and PEGylated MIL-89 (MIL-89 PEG) as suitable carriers for PAH drugs. We assessed their effects on viability and inflammatory responses in a wide range of lung cells including endothelial cells grown from blood of donors with/without PAH. Both MOFs conformed to the predicted structures with MIL-89 PEG being more stable at room temperature. At concentrations up to 10 or 30 µg/mL, toxicity was only seen in pulmonary artery smooth muscle cells where both MOFs reduced cell viability and CXCL8 release. In endothelial cells from both control donors and PAH patients, both preparations inhibited the release of CXCL8 and endothelin-1 and in macrophages inhibited inducible nitric oxide synthase activity. Finally, MIL-89 was well-tolerated and accumulated in the rat lungs when given in vivo. Thus, the prototypes MIL-89 and MIL-89 PEG with core capacity suitable to accommodate PAH drugs are relatively non-toxic and may have the added advantage of being anti-inflammatory and reducing the release of endothelin-1. These data are consistent with the idea that these materials may not only be useful as drug carriers in PAH but also offer some therapeutic benefit in their own right.

scholarly journals Cognitive therapy and exposure in vivo in the treatment of obsessive compulsive disorder

1995 ◽  
Vol 33 (4) ◽  
pp. 379-390 ◽  
Author(s):  
Patricia Van Oppen ◽  
Else De Haan ◽  
Anton J.L.M. Van Balkom ◽  
Philip Spinhoven ◽  
Kees Hoogduin ◽  
...  
Keyword(s):  
Cognitive Therapy ◽  
Obsessive Compulsive Disorder ◽  
Obsessive Compulsive ◽  
Compulsive Disorder ◽  
Exposure In Vivo

scholarly journals Localized Delivery of Amifostine Enhances Salivary Gland Radioprotection

2018 ◽  
Vol 97 (11) ◽  
pp. 1252-1259 ◽  
Author(s):  
J.J. Varghese ◽  
I.L. Schmale ◽  
D. Mickelsen ◽  
M.E. Hansen ◽  
S.D. Newlands ◽  
...  
Keyword(s):  
Salivary Gland ◽  
Side Effects ◽  
Cellular Level ◽  
Systemic Administration ◽  
Therapeutic Window ◽  
Saliva Secretion ◽  
Life Issues ◽  
Localized Delivery ◽  
Gland Function

Radiotherapy for head and neck cancers commonly causes damage to salivary gland tissue, resulting in xerostomia (dry mouth) and numerous adverse medical and quality-of-life issues. Amifostine is the only Food and Drug Administration–approved radioprotective drug used clinically to prevent xerostomia. However, systemic administration of amifostine is limited by severe side effects, including rapid decrease in blood pressure (hypotension), nausea, and a narrow therapeutic window. In this study, we demonstrate that retroductal delivery of amifostine and its active metabolite, WR-1065, to murine submandibular glands prior to a single radiation dose of 15 Gy maintained gland function and significantly increased acinar cell survival. Furthermore, in vivo stimulated saliva secretion was maintained in retrograde-treated groups at levels significantly higher than irradiated-only and systemically treated groups. In contrast to intravenous injections, retroductal delivery of WR-1065 or amifostine significantly attenuated hypotension. We conclude that localized delivery to salivary glands markedly improves radioprotection at the cellular level, as well as mitigates the adverse side effects associated with systemic administration. These results support the further development of a localized delivery system that would be compatible with the fractionated dose regimen used clinically.

Treatment of Obsessive-Compulsive Neurosis with History of Childhood Autism

1977 ◽  
Vol 130 (6) ◽  
pp. 592-597 ◽  
Author(s):  
Peter Lindley ◽  
Isaac Marks ◽  
Robin Philpott ◽  
John Snowden
Keyword(s):  
Social Skills Training ◽  
Skills Training ◽  
Childhood Autism ◽  
Obsessive Compulsive ◽  
Behavioural Treatment ◽  
History Of Childhood ◽  
History Of ◽  
Made In

SummaryA young man was followed-up over three years who had severe obsessive-compulsive rituals and ruminations, interpersonal deficits, complicating depression and a history of childhood autism. Intensive behavioural treatment was given in an operant framework, with exposure in vivo, modelling, response prevention and social skills training. Compulsive rituals improved markedly and lastingly, but ruminations and social defects persisted. When intercurrent depression occurred dothiepin facilitated behavioural treatment. Adjustment remained fragile. Minimum maintenance treatment in the community could not be adequately arranged, so that gains made in hospital were partly lost at follow-up, despite continuing improvement in rituals.

scholarly journals High Dose Lopinavir/Ritonavir Does Not Lead to Sufficient Plasma Levels to Inhibit SARS-CoV-2 in Hospitalized Patients With COVID-19

2021 ◽  
Vol 12 ◽  
Author(s):  
Mario Karolyi ◽  
Sara Omid ◽  
Erich Pawelka ◽  
Bernd Jilma ◽  
Thomas Stimpfl ◽  
...  
Keyword(s):  
Plasma Levels ◽  
Plasma Concentrations ◽  
Antiviral Effect ◽  
High Dose ◽  
Loading Dose ◽  
Reactive Protein ◽  
Net Clinical Benefit ◽  
Trough Levels

Background: Despite lopinavir/ritonavir (LPV/RTV) demonstrating in-vitro activity against SARS-CoV-2, large trials failed to show any net clinical benefit. Since SARS-CoV-2 has an EC50 of 16.4 μg/ml for LPV this could be due to inadequate dosing.Methods: COVID-19 positive patients admitted to the hospital who received high dose LPV/RTV were included. High dose (HD) LPV/RTV 200/50 mg was defined as four tablets bid as loading dose, then three tablets bid for up to 10 days. Trough plasma concentrations were measured after the loading dose and on day 5–7 in steady state (SS). Post loading dose (PLD) and SS plasma trough levels were compared with SS trough levels from COVID-19 patients who received normal dose (ND) LPV/RTV (2 tablets bid) at the beginning of the pandemic.Results: Fifty patients (30% female) with a median age of 59 years (interquartile range 49–70.25) received HD LPV/RTV. Median HD-PLD concentration was 24.9 μg/ml (IQR 15.8–30.3) and significantly higher than HD-SS (12.9 μg/ml, IQR 7.2–19.5, p < 0.001) and ND-SS (13.6 μg/ml, IQR 10.1–22.2, p = 0.013). HD-SS and ND-SS plasma levels did not differ significantly (p = 0.507). C-reactive-protein showed a positive correlation with HD-SS (Spearman correlation-coefficient rS = 0.42, p = 0.014) and ND-SS (rS = 0.81, p = 0.015) but not with HD-PLD (rS = 0.123, p = 0.43).Conclusion: HD-PLD plasma trough concentration was significantly higher than HD-SS and ND-SS concentration, but no difference was detected between HD-SS and ND-SS trough levels. Due to the high EC50 of SARS-CoV-2 and the fact that LPV/RTV is highly protein bound, it seems unlikely that LPV/RTV exhibits a relevant antiviral effect against SARS-CoV-2 in vivo.

Obsessive-compulsive Disorder in Children and Adolescents

1995 ◽  
Vol 12 (1) ◽  
pp. 51-58 ◽  
Author(s):  
Neville J. King ◽  
Thomas H. Ollendick ◽  
Iain M. Montgomery
Keyword(s):  
Obsessive Compulsive Disorder ◽  
Mental Health Professionals ◽  
Antidepressant Medication ◽  
Behavioural Intervention ◽  
Obsessive Compulsive ◽  
Behavioural Treatment ◽  
Compulsive Disorder ◽  
Relationship Of ◽  
The Relationship

This selective review shows that childhood obsessive-compulsive disorder (OCD) is a serious condition that requires early identification and treatment. Initially, we examine the relationship of childhood rituals to OCD, and discuss recent findings on the epidemiology of childhood OCD. The DSM-IV criteria for OCD are presented, along with recent findings on psychopathology. Clinical management of childhood OCD is a challenging and difficult task for mental health professionals. We briefly describe and evaluate advances in behavioural treatment — mainly in vivo exposure and response prevention. The adjunctive use of antidepressant medication is also examined. Whilst these clinical innovations are promising, further controlled evaluations are necessary before the efficacy of behavioural intervention can be confidently asserted.

scholarly journals LGD-5552, an Antiinflammatory Glucocorticoid Receptor Ligand with Reduced Side Effects, in Vivo

Endocrinology ◽  
2008 ◽  
Vol 149 (5) ◽  
pp. 2080-2089 ◽  
Author(s):  
Francisco J. López ◽  
Robert J. Ardecky ◽  
Bruce Bebo ◽  
Khalid Benbatoul ◽  
Louise De Grandpre ◽  
...  
Keyword(s):  
Side Effects ◽  
Glucocorticoid Receptor ◽  
Therapeutic Window ◽  
Glucocorticoid Treatment ◽  
Receptor Ligand ◽  
Monocyte Chemoattractant Protein 1 ◽  
Inflammatory Conditions ◽  
Differential Gene Regulation ◽  
Antiinflammatory Effects

Treatment of inflammation is often accomplished through the use of glucocorticoids. However, their use is limited by side effects. We have examined the activity of a novel glucocorticoid receptor ligand that binds the receptor efficiently and strongly represses inflammatory gene expression. This compound has potent antiinflammatory activity in vivo and represses the transcription of the inflammatory cytokine monocyte chemoattractant protein-1 and induces the antiinflammatory cytokine IL-10. The compound demonstrates differential gene regulation, compared with commonly prescribed glucocorticoids, effectively inducing some genes and repressing others in a manner different from the glucocorticoid prednisolone. The separation between the antiinflammatory effects of LGD-5552 and the side effects commonly associated with glucocorticoid treatment suggest that this molecule differs significantly from prednisolone and other steroids and may provide a safer therapeutic window for inflammatory conditions now commonly treated with steroidal glucocorticoids.

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