Binding interactions with sevelamer and polystyrene sulfonate in vitro

This study explored the binding of 28 drugs, which were selected based on frequency of concomitant use and chemical properties, to sevelamer and polystyrene sulfonate in vitro. The relative binding was determined by dissolving the investigated drugs alone (=control), together with 800 mg of sevelamer and 15 g of polystyrene sulfonate at different pH levels (1.5, 5.5, and 7.4), respectively. After incubation at 37℃ and shaking for 60 min, the solutions were diluted and centrifuged, and the drug concentrations were quantified with validated analytical assays. The binding assays were performed in threefold. The mean relative binding (MRB) at each pH level was calculated, with a MRB >20% for at least one pH level to be considered as relevant binding. Fourteen and 23 potentially new binding interactions were identified with sevelamer and polystyrene sulfonate, respectively. These potentially new binding interactions have to be studied in vivo to assess their clinical relevance

Lean Body Mass and Total Body Weight Versus Body Surface Area as a Determinant of Docetaxel Pharmacokinetics and Toxicity

Aim:This study examined whether anthropometric and body composition parameters such as body surface area (BSA), lean body mass (LBM), and total body weight (TBW) are correlated with docetaxel clearance and exposure by analyzing area under the curve. In addition, LBM, TBW, and a fixed dose were compared with BSA as dosing parameters for dose individualization of docetaxel.Methods:Thirty-six patients receiving docetaxel chemotherapy for breast or metastatic castration-resistant prostate carcinoma were included. Before treatment, LBM was measured using a dual-energy X-ray absorptiometry scanner. Blood samples were collected up to 180 minutes after dosing to analyze docetaxel concentrations and determine individual pharmacokinetic parameters.Results:No significant correlations were found between docetaxel clearance and the anthropometric and body composition variables (BSA, LBM, and TBW). The area under the curve was significantly but poorly correlated with BSA [r = 0.452 (P = 0.016)] and TBW [r = 0.476 (P = 0.011)]. The mean absolute percentage error and mean error of simulated dosing based on LBM and fixed dosing were not significantly different from those of BSA. For TBW, only mean absolute percentage error was significantly higher compared with dosing based on BSA (24.1 versus 17.1, P = 0.001).Conclusions:There was no clinically relevant correlation between docetaxel pharmacokinetics and the anthropometric and body composition variables BSA, LBM, and TBW. Therefore, dose individualization of docetaxel based on LBM, TBW, or fixed dosing cannot be recommended over BSA-based dosing