Psychopharmacology of Attention Deficit Disorder: Pharmacokinetic, Neuroendocrine, and Behavioral Measures Following Acute and Chronic Treatment with Methylphenidate

PEDIATRICS ◽  
1982 ◽  
Vol 69 (6) ◽  
pp. 688-694
Author(s):  
Sally E. Shaywitz ◽  
Robert D. Hunt ◽  
Peter Jatlow ◽  
Donald J. Cohen ◽  
J. Gerald Young ◽  
...  

Despite the frequent use of methylphenidate (MPH) in school-aged children with disorders of attention, impulsivity, and activity regulation (attention deficit disorder, ADD), little is known of its clinical pharmacology. The pharmacokinetics of MPH as well as its effects on growth hormone and prolactin were examined after oral administration in 14 boys with ADD ranging in age from 7 to 12 years (mean 10.4 years). Peak concentrations determined in these acute studies were compared with concentrations obtained two hours after MPH administration in another group of children with ADD who were receiving MPH chronically. After a lag phase of approximately ½ to 1 hour, MPH reached a peak plasma concentration at 2.5 ± 0.65 hours after 0.34 mg/kg and 1.9 ± 0.82 hours after 0.65 mg/kg (mean ± SD). Terminal half-lives were 2.53 ± 0.59 and 2.61 ± 0.29 hours after administration of 0.34 and 0.65 mg/kg, respectively. Observed maximal concentrations ranged from 11.2 ± 2.7 ng/ml after administration of 0.34, and 20.2 ± 9.1 ng/ml after administration of 0.65 mg/kg. The mean area under the curve after administration of 0.65 mg/kg was approximately double that calculated at 0.34 mg/kg. Plasma growth hormone increased significantly from an initial (pre-MPH) mean concentration of 4.4 to peak at two hours at 10.5 ng/ml. Prolactin concentration declined significantly from a pre-MPH level of 9.5 to a nadir at 1½ hours of 3.80 ng/ml, supporting the notion that MPH is acting via central dopaminergic mechanisms. MPH concentrations in children receiving doses of 0.34 mg/kg chronically averaged 8.00 ± 0.91 at two hours, after medication, approximating the mean concentration at the same time observed in the acute study. The concentration of MPH in single "spot" samples obtained at two to three hours after administration of medication were significantly correlated with the percentage of improvement in the abbreviated Conners rating scale, indicating a relationship between plasma MPH concentration and clinical response.

2021 ◽  
Vol 12 ◽  
Author(s):  
Abhijeet K. Kohat ◽  
Samuel Y. E. Ng ◽  
Aidan S. Y. Wong ◽  
Nicole S. Y. Chia ◽  
Xinyi Choi ◽  
...  

Background: Various classifications have been proposed to subtype Parkinson's disease (PD) based on their motor phenotypes. However, the stability of these subtypes has not been properly evaluated.Objective: The goal of this study was to understand the distribution of PD motor subtypes, their stability over time, and baseline factors that predicted subtype stability.Methods: Participants (n = 170) from two prospective cohorts were included: the Early PD Longitudinal Singapore (PALS) study and the National Neuroscience Institute Movement Disorders Database. Early PD patients were classified into tremor-dominant (TD), postural instability and gait difficulty (PIGD), and indeterminate subtypes according to the Movement Disorder Society's Unified PD Rating Scale (MDS-UPDRS) criteria and clinically evaluated for three consecutive years.Results: At baseline, 60.6% patients were TD, 12.4% patients were indeterminate, and 27.1% patients were PIGD subtypes (p < 0.05). After 3 years, only 62% of patients in TD and 50% of patients in PIGD subtypes remained stable. The mean levodopa equivalent daily dose (LEDD) was higher in the PIGD subtype (276.92 ± 232.91 mg; p = 0.01). Lower LEDD [p < 0.05, odds ratio (OR) 0.99, 95% confidence interval (CI): 0.98–0.99] and higher TD/PIGD ratios (p < 0.05, OR 1.77, 95% CI: 1.29–2.43) were independent predictors of stability of TD subtype with an area under the curve (AUC) of 0.787 (95%CI: 0.669–0.876), sensitivity = 57.8%, and specificity = 89.7%.Conclusion: Only 50–62% of PD motor subtypes as defined by MDS-UPDRS remained stable over 3 years. TD/PIGD ratio and baseline LEDD were independent predictors for TD subtype stability over 3 years.


2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 381-381
Author(s):  
Yavuz Yagiz ◽  
Gary Wang ◽  
Liwei Gu

Abstract Objectives Berberine is a botanical alkaloid used widely for the prevention of several diseases. However, the absorption rate of berberine is less than 1% in human. The objectives of this study were to determine whether emulsification by TPGS or Quillaja extract affect the absorption and metabolism of orally ingested berberine in human volunteers. Methods Twelve healthy subjects (7 male and 5 females, 21–50-year-old) participated this study. Each subject received 800 mg berberine in a powder form or emulsified with TPGS or Quillaja extract using a randomized crossover design with one-week washout period. Blood samples were collected at 0, 0.5, 1, 2, 3, 4, 6, 8, and 12 hours after dose. Plasma was hydrolyzed with glucuronidase and sulfatase before total content of berberine and its metabolites were analyzed on LC/MS/MS. Free forms of metabolites were determined in plasma without hydrolysis. Pharmacokinetic parameters were calculated using a non-compartment model before they were compared by analysis of covariance. Results The area under the curve (AUC) and peak plasma concentration (Cmax) of berberine was 6.6 μM.hr and 0.9 μM in participants received berberine powder. They were increased to 18.3 μM.hr and 4.5 μM by TPGS emulsification and 28 μM.hr and 5.1 μM by Quillaja extract emulsification, respectively. Berberrubine and demethylberberine were major metabolites of berberine. The AUC of free Berberrubine and demethylberberine was increased by 1.9 fold and 1.6 fold by TPGS and 5.9 folds and 2.7 folds by Quillaja extract, respectively, compared to berberine powder. Participants received berberine powder had AUC of 254 μM.hr and Cmax of 33 μM for total berberrubine. TPGS emulsification increased these values to 425 μM.hr and 54 μM, while Quillaja extract increased them to 341 μM.hr and 44 μM, respectively. Significant increases of AUC and Cmax were also observed for total demethylberberine by TPGS or Quillaja extract emulsification. Conclusions Emulsification of berberine with TPGS or Quillaja extract significantly increased the absorption of berberine and its metabolites in human compared to berberine supplement without emulsifiers. Funding Sources Florida High Tech Corridor Council and Designs for Health.


1982 ◽  
Vol 10 (5) ◽  
pp. 379-382 ◽  
Author(s):  
Kari Soininen ◽  
Hannu Allonen ◽  
Juhani Posti

The bioavailability of the calcium and potassium salts of Phenoxymethylpenicillin (dose 38,000 I.U./kg) was investigated in eight healthy adult volunteers. Administration of the calcium salt as an aqueous oral mixture resulted in a mean peak plasma concentration of 8·52 mg/l (SD 1·96) and that of the potassium salt mixture in a concentration of 8·40 mg/ml (SD 2·61), p > 0·1. The median time-to-peak levels were 0·75 h and 1·0 h, respectively (p > 0·1). The mean AUC for the calcium salt mixture was 16·94 mg·h/l (SD 3·31) and for the potassium salt 15·84 mg·h/l (SD 4·76), p > 0·09. These findings confirm that an aqueous mixture of calcium phenoxymethylpenicillin is equivalent to a mixture of potassium Phenoxymethylpenicillin.


Life Sciences ◽  
1990 ◽  
Vol 46 (9) ◽  
pp. 625-633 ◽  
Author(s):  
Bennett A. Shaywitz ◽  
Sally E. Shaywitz ◽  
Mark M. Sebrechts ◽  
George M. Anderson ◽  
Donald J. Cohen ◽  
...  

PEDIATRICS ◽  
1994 ◽  
Vol 93 (1) ◽  
pp. 70-75 ◽  
Author(s):  
Bennett A. Shaywitz ◽  
Colleen M. Sullivan ◽  
George M. Anderson ◽  
Sheila M. Gillespie ◽  
Barbara Sullivan ◽  
...  

Objective. To determine the effects of large doses of aspartame on behavior, cognition, and monoamine metabolism in children with attention deficit disorder. Design. A randomized, double-blind, placebo-controlled crossover study of unmedicated children meeting Diagnostic and Statistical Manual of Mental Disorders (3rd ed) criteria for attention deficit disorder. Setting. Behavioral assessments were performed in the child's home by their parents and in the classroom by a teacher. Cognitive tests were administered and blood drawing was performed during a 2-day inpatient admission to our Children's Study Center. Interventions. Administration of aspartame (single morning dose, 34 mg/kg) or placebo for alternate 2-week periods. Main outcome measures. Behavioral and cognitive tests included the Matching Familiar Figures Test (MFFT), Children's Checking Task (CCT), the Airplane Test, the Wisconsin Card Sorting Test (WCST), the Subjects Treatment Emergent Symptom Scale (STESS), the Multigrade Inventory for Teachers (MIT), and the Conners Behavior Rating Scale. Blood was drawn for complete blood cell count and liver function tests, as well as amino acid, methanol, formate, serotonin, and monoamine metabolite analyses, and urine was collected for measurement of catecholamine and monoamine metabolite excretion. Results. No clinically significant differences between aspartame and placebo were found for the STESS, MIT, or Conners ratings, or for the MFFT, CCT, WCST, or Air-plane cognition tests. Also, no differences were noted for any of the biochemical measures, except for the expected increase in plasma phenylalanine and tyrosine following aspartame. Conclusions. The findings indicate that aspartame at greater than 10 times usual consumption has no effect on the cognitive and behavioral status of children with attention deficit disorder. In addition, aspartame does not appear to affect urinary excretion rates of monoamines and metabolites.


Author(s):  
Ameneh Panah ◽  
Shahram Zare

The purpose of this study was to determine the prevalence of attention deficit disorder/hyperactivity in medical students of Bandar Abbas University of Medical Sciences in 2011-2014. This research is a descriptive study. In this study, 176 students were selected through available sampling among medical students from Bandar Abbas University of Medical Sciences from 2011 to 2014.In this study, the Wender Utah and rating scale were completed by students through self-reporting The population of the study included 176 students who 105 were female students, and 71 were male students. Based on the findings of this study, the rate of attention deficit disorder hyperactivity among students was 1.7%, and 10.8% of students were suspected of this disorder. In this study, there was no statistically significant relationship between the items such as gender, marital status, age, total score, and history of mental disorders and mean scores for attention-deficit / hyperactivity disorder. The prevalence of attention deficit disorder hyperactivity in students is significant. Due to the interactions that this disturbance causes in the student's academic and occupational performance, student assessments should be made at university registration as well as at university by the academic advisers in order to diagnose and treat them.


2013 ◽  
Vol 28 (S2) ◽  
pp. 47-47
Author(s):  
M. Di Nicola ◽  
L. Sala ◽  
L. Romo ◽  
V. Catalano ◽  
C. Dubertret ◽  
...  

IntroductionDans les cas des troubles bipolaires, les taux de comorbidité avec un TDAH peut varier entre 9,5 % et 27 % [1]. Ces patients présentent un début de trouble plus précoce, avec plus d’épisodes dépressifs et des épisodes mixtes. Il existe peu d’étude sur le lien entre ces deux pathologies et les différentes dimensions de personnalité selon le modèle de Big Five. MethodsNotre étude comporte 106 patients souffrant de dépression, 102 patients bipolaires et 120 témoins, tous homogènes vis-à-vis de leurs caractéristiques démographiques. Le diagnostic de TDAH se basait sur les critères DSM-IV-TR. Les traits de TDAH étaient autoévalués avec la Wender Utah Rating Scale (WURS), la Adult ADHD Self-rating Scale (ASRS) et la Brown Attention Déficit Disorder Scale (ADD). L’Inventaire de Personnalité-Révisé, le NEO PI-R, servait également à évaluer les dimensions de la personnalité au sein des groupes cliniques. Résultats15,7 % des adultes souffrant d’un trouble bipolaire et 7,5 % souffrant d’une dépression sévère manifestaient une comorbidité d’un TDAH en comparaison avec seulement 3,3 % des témoins. Il existe des corrélations significatives entre des traits de personnalité et la présence d’un TDAH. Une analyse de régression logistique de l’ensemble des 208 sujets cliniques a montré que ceux avec des faibles niveaux de névrosisme manifestaient un taux moins important de comorbidité avec un TDAH. DiscussionNotre étude souligne le lien entre des troubles de l’humeur, notamment les troubles bipolaires, et la présence d’un TDAH chez des adultes. Nos résultats soutiennent la nécessité d’évaluer les sujets souffrant des troubles d’humeur sur une éventuelle comorbidité de TDAH en milieu clinique. Il faudra étudier d’une façon plus approfondie ces traits de personnalité et les liens entre des troubles de l’humeur et un TDAH afin de pouvoir adapter la prise en charge.


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