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The pharmacokinetics (PK) of tenecteplase in patients with acute ischemic stroke has not been extensively studied. This study aimed to describe PK characteristics of tenecteplase in patients with acute myocardial infarction (AMI) using a population PK approach and to assess applicability of the findings to patients with acute ischemic stroke by means of external validation. A population PK model was developed using nonlinear mixed-effects modeling based on the phase II TIMI 10B study in patients with AMI (785 PK observations from 103 patients). The statistical and clinical impact of selected covariates on PK parameters were evaluated by a stepwise covariate modeling procedure and simulations, respectively. The performance of the final model was evaluated for patients with acute ischemic stroke using summary statistics of tenecteplase concentrations of 75 patients from investigator-initiated study N1811s. Tenecteplase PK was well described by a 2-compartment linear model, incorporating allometric scaling of clearance and volume parameters and weight-normalized creatinine clearance on clearance. Simulations showed that the identified covariates (weight and creatinine clearance) were of limited influence on exposure at the intended dosing regimen for patients with acute ischemic stroke. The model overpredicted mean tenecteplase plasma concentrations from N1811s by 39%, but 72% of the distribution from N1811s was within the 90% prediction interval of the model predictions. The PK characteristics of tenecteplase in patients with AMI were well described by the final model. Simulations from the model indicated that no specific dose recommendations based on covariates are warranted for patients with AMI. [ABSTRACT FROM AUTHOR]

Background: Iodine quantification using dual-energy computed tomography (DECT) is helpful in characterizing, and follow-up after treatment of tumors. Some malignant masses, for instance papillary renal cell carcinomas (p-RCC), are hard to differentiate from benign lesions because of very low contrast enhancement. In these cases, iodine concentrations might be very low, and it is therefore important that iodine quantification is reliable even at low concentrations if this technique is used. Purpose: To examine the accuracy of iodine quantification and to determine whether it is also accurate for low iodine concentrations. Material and Methods: Twenty-six syringes with different iodine concentrations (0–30 mg I/mL) were scanned in a phantom model using a DECT scanner with two different kilovoltage and image reconstruction settings. Iodine concentrations were measured and compared to known concentration. Absolute and relative errors were calculated. Results: For concentrations of 1 mg I/mL or higher, there was an excellent correlation between true and measured iodine concentrations for all settings (R = 0.999–1.000; P < 0.001). For concentrations <1.0 mg I/mL, the relative error was greater. Absolute and relative errors were smaller using tube voltages of 80/Sn140 kV than 100/Sn140 kV (P < 0.01). Reconstructions using a 3.0-mm slice thickness had less variance between repeated acquisitions versus 0.6 mm (P < 0.001). Conclusion: Iodine quantification using DECT was in general very accurate, but for concentrations < 1.0 mg I/mL the technique was less reliable. Using a tube voltage with larger spectral separation was more accurate and the result was more reproducible using thicker image reconstructions. [ABSTRACT FROM AUTHOR]