Paliperidone palmitate (PP) is a long-acting injectable (LAI) antipsychotic, developed for monthly intramuscular (i.m.) administration into deltoid/gluteal muscle, approved for the treatment of schizophrenia in many countries. To assess the options for i.m. injection sites, dose-proportionality of PP was investigated after injection of a single dose (25-150 mg eq.) of PP in either gluteal (n = 106) or deltoid (n = 95) muscle of schizophrenic patients. Overall, mean (geometric) area under plasma concentration-time curve from time zero to infinity (AUC∞ ) of paliperidone increased proportionally with increasing PP doses, regardless of injection site. Mean maximum plasma concentration (Cmax ) was slightly less than dose-proportional for both injection sites at PP doses >50 mg eq. Mean Cmax was higher after injection in the deltoid compared with the gluteal muscle, except for the 100 mg eq. dose, while AUC∞ for both injection sites was comparable at all doses. Median time to reach Cmax (tmax ) ranged from 13-14 days after deltoid and 13-17 days after gluteal injection across all doses. Single PP injections in deltoid and gluteal muscles in the dose range of 25-150 mg eq. were generally tolerable both locally and systemically.

BackgroundLevetiracetam (LEV) is a second-generation antiepileptic drug used as a unique or adjunctive therapy for treating partial or generalised epilepsy. Its maximum dose according to the summary product is 3000 mg/day. In patients with resistant epilepsy sometimes it is used at doses higher than recommended. A recent report suggests that high doses may still be possible without toxicity.1 PurposeTo describe the importance of therapeutic drug monitoring (TDM) of LEV for minimising toxicity when it is used at doses higher than recommended.Material and methodsCase report of 57-years-old male diagnosed with symptomatic focal epilepsy and human immunodeficiency virus (HIV). Antiepileptic treatment consists of LEV 4000 mg/day, topiramate 300 mg/day and clonazepam 4 mg/day since 2010 plus lacosamide 200 mg/day added in 2015. In September 2016 he had a new neurological crisis and dosage was increased to 4500 mg/day. Antiretroviral medication (AM) was changed in 2013 from tenofovir/efavirenz/emtricitabine to abacavir/lamivudine plus efavirenz. In January 2017 AM medication was simplified to dolutegravir/abacavir/lamivudine.ResultsLEV trough plasma levels (LEVTPL) were 35.9 µg/mL (therapeutic range is 10–40 µg/mL) at the beginning of 2016, 6 years after treatment with LVT 4000 mg/day, glomerular filtration (GFR) calculated by CKD-EPI was >60 ml/min/1.73 m2 and the patient did not have clinical signs of toxicity. Three months after increasing LEV dose to 4500 mg/day the patient presented symptoms of intoxication, felt tired and sleepy. TDM confirmed supratherapeutic LEVTPL of 67.1 µg/mL accompanied by a slight deterioration of renal function (GFR: 50 ml/min/1.73 m2). Concomitant medication seemed not to interact with LEV. LEV dose was reduced to 3500 mg/day. Three months’ later, LEVTPL values returned to normal (36.3 µg/mL) and clinical signs of toxicity disappeared.ConclusionLEV at doses higher than recommended could be used safely if there is a close TDM programme to ensure treatment effectiveness and minimise adverse effects.References and/or Acknowledgements1. Stepanova D, Beran R. Measurement of levetiracetam drug levels to assit with seizure control and monitoring of drug interactions with other Anti-Epileptic Medication (AEMs). Seizure2014;23:371–376.No conflict of interest

BackgroundA large variability in biopharmaceutical kinetics exists between patients and even within a patient over time. Also, adequate thorough concentrations are linked to response in psoriasis.Therapeutic drug monitoring of biopharmaceuticals (i.e. infliximab–IFX) together with clinical response allows targeted cost-effective dose-adjustments.PurposeThe aim of the present study was to evaluate the real-life association between IFX exposure and clinical outcomes in patients with psoriasis.Material and methodsProspective study in psoriatic patients receiving IFX, between October 2013 and November 2016. We measured Cmin and antibodies towards IFX (ATI) using an enzyme-linked immunosorbent assay (ELISA) kit. Data on demographic, analytical and pharmacological variables and Psoriasis Area Severity Index (PASI) were recorded. Mixed models were estimated to evaluate association between IFX through concentrations (Cmin) and clinical response. Statistical analysis was carried out using R.ResultsWe used a total of 155 Cmin values and ATI from 33 patients (33% females). Weight: 88.2 Kg (±23.5), BMI: 31 Kg/m2 (±2.2), PASI at blood sampling: 2.2 (±3.2), PASI score reduction:% (±) (normal weight: 79% (±32.4), overweight: 78.2% (±35) and obese: 76.3% (±31)). Percentage of PASI 75, 90 and 100 response: 78.8%, 60.6% and 54.5%, respectively.The median Cmin was 2.4 mg/L (±2.2) (normal weight: 1.64 mg/L, overweight: 2.68 mg/L and obese: 2.68 mg/L). Six patients tested ATI positive and had undetectable Cmin. Patients achieving PASI 75 had a significantly higher Cmin than non-responders (2.86 vs 1.58 mg/L, p<0.001). Similar results were obtained for PASI 90 and 100 responses.PASI score was significantly influenced by Cmin (IRR: 0.79, 95% CI: 0.69 to 0.91). This remained significant when adjusting by sex, BMI, diagnose, baseline PASI, leukocyte count, ATI status and immunomodulator treatment (IRR: 0.80, 95% CI: 0.70 to 0.93). Same results were obtained for PASI 90 and 100 responses (OR: 1.79, 95% CI: 1.14 to 2.81; OR:.1.79, 95% CI: 1.18 to 2.71 respectively).ConclusionPASI score and achievement of PASI 90 response or higher were significantly influenced by IFX Cmin.The percentage of patients achieving PASI 75 or higher decreased with BMI, while Cmin values increased.No conflict of interest