Home About us Contact
|
Home About us Contact | ||
|
|
||
PD Relationship (pd + relationship)
Selected AbstractsPharmacokinetic,pharmacodynamic study of apomorphine's effect on growth hormone secretion in healthy subjectsFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 4 2003Guy Aymard Abstract Apomorphine (APO) stimulates growth hormone (GH) release via dopamine D2 receptors (DRD2). There is no specific study assessing the relationship between APO pharmacokinetic (PK) and the pharmacodynamic (PD) response e.g. GH release. The objective of the study is the PK,PD modelling of APO in healthy subjects. This is a randomized crossover study with s.c. administration of 5, 10, and 20 ,g/kg of APO in 18 healthy subjects. APO concentrations were modelled according to both a bi-compartmental model with zero-order absorption and a bi-compartmental model with first-order absorption. PK,PD relationship was modelled in accordance with the Emax Hill equation using plasma concentrations of APO calculated according to the bi-compartmental model with zero-order absorption. Modelled parameters were very similar to the experimental parameters. PK of APO was linear and there was no significant difference between the tested doses for AUC0,, and Cmax (normalised to the dose 1 ,g/kg), t1/2, and t1/2,. These parameters expressed as mean (CV%: SD/mean) were: 17.2 (26.9) ng/mL·min, 0.26 (33.3) ng/mL, 17.1 (54.2) and 45.2 (20.6) min, respectively (n = 53). An anticlockwise hysteresis loop (effect function of APO plasma concentration) appeared for each dose and each subject. The predicted and measured GH concentrations for all subjects and times were similar whatever the dose (P > 0.27). Emax values were 246 (121), 180 (107), 205 (139) ng/mL, respectively, and EC50 were 0.98 (48.1), 1.70 (62.3), 3.67 (65.2) ng/mL, respectively at dose 5, 10, and 20 ,g/kg (P < 10,4). APO and GH concentrations were predicted with good accuracy using bi-compartmental with zero-order absorption PK model and sigmoid Emax PD model, respectively. [source] Does social problem solving mediate the relationship between personality traits and personality disorders?PERSONALITY AND MENTAL HEALTH, Issue 3 2010An exploratory study with a sample of male prisoners Background Social problem solving therapy is one helpful approach to treating people with personality disorders (PD). Consequently, it is worthwhile to develop a greater understanding of the role of social problem solving in PD. One hypothesis is that social problem solving mediates the relationship between personality dimensions and personality disorder. This premise was explored in a sample of male prisoners, a population known to have a high prevalence of PD. Method Sixty-eight men completed the International Personality Disorder Examination (IPDE), NEO-Five Factor Inventory (NEO-FFI) and the Social Problem-Solving Inventory,Revised: Short Version (SPSI-R:S). The data were explored for direct and indirect mediational effects of social problem solving variables in the personality dimension,PD relationship, using methods appropriate for small samples and multiple mediators. Results A number of relationships between personality dimensions, social problem solving, and personality disorder traits were identified, but only for paranoid, schizotypal, borderline, narcissistic, and avoidant PDs. Discussion These findings support the hypothesis that social problem solving mediates between personality dimensions and some PDs. Further research is necessary to verify these relationships. However, these findings begin to clarify the mechanisms by which personality dimensions relate to PDs. This knowledge has potential to contribute to the development of more effective interventions for people with particular personality dimensions and specific personality disorders. Copyright © 2010 John Wiley & Sons, Ltd. [source] Lamotrigine pharmacokinetic/pharmacodynamic modelling in ratsFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 6 2005M.M. Castel-Branco Abstract The aim of this study was to perform a pharmacokinetic/pharmacodynamic (PK/PD) modelling of lamotrigine following its acute administration to rats. Adult male Wistar rats were given 10 mg/kg of lamotrigine intraperitoneally. Plasma and brain samples were obtained at predetermined times over 120 h post-dose and analysed by liquid chromatography. The anticonvulsant profile against maximal electroshock seizure stimulation was determined over 48 h after dosing. As a linear relationship between lamotrigine plasma and brain profiles was observed, only the plasma data set was used to establish the PK/PD relationship. To fit the effect,time course of lamotrigine, the PK/PD simultaneous fitting link model was used: the pharmacokinetic parameters and dosing information were used in the one-compartment first-order model to predict concentrations, which were then used to model the pharmacodynamic data with the sigmoid Emax model, in order to estimate all the parameters simultaneously. The following parameters were obtained: Vd = 2.00 L/kg, kabs = 8.50 h,1, kel = 0.025 h,1, ke0 = 3.75 h,1, Emax = 100.0% (fixed), EC50 = 3.44 mg/L and , = 8.64. From these results, it can be stated that lamotrigine is extensively distributed through the body, its plasma elimination half-life is around 28 h and a lamotrigine plasma concentration of 3.44 mg/L is enough to protect 50% of the animals. When compared with humans, the plasma concentrations achieved with this dose were within the therapeutic concentration range that had been proposed for epileptic patients. With the present PK/PD modelling it was possible to fit simultaneously the time-courses of the plasma levels and the anticonvulsant effect of lamotrigine, providing information not only about the pharmacokinetics of lamotrigine in the rat but also about its anticonvulsant response over time. As this approach can be easily applied to other drugs, it becomes a useful tool for an explanatory comparison between lamotrigine and other antiepileptic drugs. [source] Nonlinear mixed effects pharmacokinetic/pharmacodynamic analysis of the anticonvulsant ameltolide (LY201116) in a canine seizure modelJOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 6 2008P. R. TERRITO The anticonvulsant ameltolide (LY201116) is a novel potential therapy for the treatment of canine epilepsy. Eight dogs were administered five different oral doses of ameltolide and clinical scoring of the maximal electroshock (MES) induced seizures at 3 and 24 h postdosing were determined in two separate crossover design studies. Plasma ameltolide concentrations were determined at the time of seizures in all dogs and complete plasma concentration-time profiles were also determined in a separate study. A nonlinear mixed effects PK/PD model was fit to the resulting data. A one compartment open model with first order absorption was determined to best fit the ameltolide pharmacokinetics. An effect compartment with a cumulative logistic regression equation was used to establish the PK/PD relationship. The mean bioavailability normalized volume of distribution and the elimination half-life were estimated at 1.20 L/kg and 5.46 h, respectively. The fitted model estimated that from 2 to 15 h following a single 3 mg/kg oral ameltolide dose the mean probability of obtaining a 1 unit reduction in the seizure clinical score severity was greater than 0.80. The utilized PK/PD analysis combined with the canine MES model allowed for the rapid and efficient determination of the plasma ameltolide concentration-anticonvulsant relationship preclinically in dogs. [source] | ||||||||||