Search

Contains fulltext : 229080.pdf (Publisher’s version ) (Closed access) Recently in a national newspaper presumed large hazards in care were described. Visible black particles were seen in blood plasma and a cancerogenic substance was found in paracetamol. Every year 300.000 bags of plasma are produced. The black particles were found in 11 bags of plasma. Possibly one of these was administered. During administration 175 micron filters are used. Presumably remaining particles will be degraded by the mononuclear-phagocytic system. In paracetamol 6 ppm of para-chloroaniline was found. Depending of the limit used by either the ICH or the EFSA this means for patients using lifelong 6 grams of paracetamol a risk off respectively 1: 200.000 or 1:20.000. This risk is neglectable compared of the life time risks of cancer in the population (1:3). Journalists should realize that this exaggerated commentary can lead to real serious risks (taking NSAID's instead of paracetamol) and mistrust in regular care.

Contains fulltext : 174730.pdf (Publisher’s version ) (Closed access) Tyrosine kinase inhibitors (TKIs) play an important role in cancer pharmacotherapy, yet there is limited data on their use during pregnancy. We studied placental disposition and placental toxicity of crizotinib, a TKI used to treat nonsmall cell lung cancer. Term placentas were perfused for 3 h with crizotinib (1 microM) using the ex vivo dual-side cotyledon perfusion technique. Interference of TKIs with trophoblast viability was studied using BeWo cells. Expression of P-glycoprotein (P-gp) and Breast Cancer Resistance Protein (BCRP) in placental tissue was assessed by immunohistochemistry and inhibition of these transporters was determined in vitro by transport studies with membrane vesicles overexpressing human P-gp or BCRP. We found that crizotinib rapidly and strongly accumulates in cotyledon perfusion experiments, reaching a concentration of 3.1 +/- 0.4 microM in placental tissue. Final drug concentrations in the maternal and foetal reservoirs were 0.2 +/- 0.05 and 0.08 +/- 0.01 microM, respectively. Furthermore, crizotinib inhibited BeWo cell viability (IC50: 234 nM, 95% CI: 167-328 nM) 10 times more potently than other TKIs tested. In vitro transport studies revealed that crizotinib is a potent inhibitor of the transport activities of BCRP (IC50: 5.7 microM, 95% CI: 2.7-11.8 microM) and P-gp (IC50: 7.8 microM, 95% CI: 3.4-18.0 microM). In conclusion, crizotinib strongly accumulated in placental tissue at clinically relevant concentrations. IC50 values for transporter inhibition and trophoblast cell viability were similar to the tissue concentrations reached, suggesting that crizotinib can inhibit placental BCRP and P-gp function and possibly affect trophoblast viability.

Item does not contain fulltext