Amphetamine Versus Non Amphetamine-Related First Episode Psychosis in Saudi Arabian Patients

Background: Amphetamines are illicit psychostimulant drugs that can induce psychotic symptoms. Very few studies have been conducted in Kingdom of Saudi Arabia (SA) on amphetamine abuse and related psychosis. Recently, the pattern of amphetamine abuse in SA showed a significant trend of increased frequency. Objectives: To investigate the extent of amphetamine abuse in a sample of Saudi patients hospitalized for first episode of acute psychosis. Also, to compare in that sample between amphetamine psychosis and other psychoses regarding demographic data, premorbid personality and symptoms profile. Method: 106 patients with acute psychosis were hospitalized and screening of urine for amphetamine was conducted for all. Patients’ psychiatric evaluation included interviewing, and ICD-10 criteria for personality disorders. 30 healthy subjects were also included for comparison with patients. Results: 34/106 of psychotic patients (32%) were positive for amphetamine in urine (≥ 1000 ng/ml). The frequency of personality disorders was significantly higher (P < 0.01) in the patients (54/106;51%) compared with healthy subjects (6/30;20%). Also, the incidence of personality disorders was significantly higher (P < 0.01) in amphetamine positive psychosis (25/34;73.5%) compared with amphetamine negative psychosis (29/72;40%). Cluster B personality disorders particularly the antisocial and borderline were significantly higher in amphetamine positive psychosis (13/34;38%) compared with amphetamine negative psychoses (6/72;8%). The symptom profile showed significant difference between amphetamine positive and amphetamine negative psychosis as regards ideas of reference (50% vs. 14%), suspiciousness (44% vs. 11%), suicidal ideation (38% vs. 23%), paranoid delusions (29% vs. 17%) and increased pulse or blood pressure (29% vs. 7%) respectively. Conclusion: Screening of amphetamine in urine among patients with first episode of acute psychosis can help and support the clinical distinction of amphetamine psychosis from other types of psychosis. This is therapeutically critical since the line of treatment may be different between the two types of psychoses.

Population Pharmacokinetics of Methotrexate in Egyptian Children with Lymphoblastic Leukemia

Background: Individualization of high dose regimen of methotrexate (MTX) in pediatric patients with acute lymphoblastic leukemia based on pharmacokinetic (PK) parameters can help in optimization of the dose and better control of the disease. Building up of a pharmacokinetic model can help dose optimization. Objectives: A NONMEM based population (POP) PK model has been subsequently developed to evaluate the effect of demographics as covariates to address variability in pharmacokinetics of MTX. Method: Forty one patients (24 males & 17 females) with ranges of age, body weight and height of 3 - 15 years, 13 - 54 kg and 100 - 177 cm respectively and diagnosed as acute lymphoblastic leukemia (ALL) were involved in the study. MTX was administered as i.v. infusion at a dose of 2 gm/m2 over a period of two hour and its plasma concentrations were determined primarily at 24 hr post-dose to be utilized in the building-up of PK model.The initial/prior estimates of volumes of central (V1) and peripheral compartments (V2) and clearance (CL) and inter-compartmental clearance (Q2) for MTX were extracted from literature. The inter-subject variability was estimated for V1 & CL. The influence of different covariates on model performance and parameter estimates was assessed by evaluating the difference in objective function value. The final POP PK model was validated by bootstrap re-sampling procedures (1000 runs) and the 95% confidence intervals for the estimates were calculated. Results: The POP estimates for CL, V1 and V2 were 2.18 L/h, 5.74 L and 11.2 L respectively. The inter-individual variability for the CL and V1 was 23% and 30% respectively. The covariates analysis showed effect of body surface area and sex on the CL and weight on V1. Conclusions: The POP-PK model developed adequately defines the population PK of MTX in pediatric patients with lymphoblastic leukemia. The model showed effect of body surface area and sex on clearance and weight on volume of distribution of the MTX. Further studies are required on larger number of patients with enrichment of samples for MTX concentrations. The developed PK model should be also investigated in correlation with the genotyping style of different MTX transporters that may affect MTX PK parameters.