The use of neoplastic donors to increase the donor pool

The aim of the study was to evaluate the experience of the Centre-Sud Transplant Organization (OCST) area using cadaveric donor with neoplastic diseases to evaluate the possibility of transmission to recipients. From January 1, 2003, to December 31, 2010, the neoplastic risk has been reported to be 5.4% (377/4654 referred donors). In 2003, the number of donors with a tumor and their mean age were respectively: 60 (10.3%) and 59.6 ± 19.9; 2004: 33 (5.2%) and 61.4 ± 15.9; 2005: 32 (6%) and 62.8 ± 15.5; 2006: 46 (7%) and 60.7 ± 19.1; 2007: 51 (7%) and 58.9 ± 16; in 2008: 58 (7%) and 59.7 ± 19.6; 2009: 47 (7%) and 57 ± 26; 2010: 49 (7%) and 64 ± 16. The organ most affected by tumor has been the central nervous system (18%). The tumor was diagnosed before in 325 (86%) cases, versus during organ retrieval in 48 (12.7%) donor operations but before, which four cases (1%) occured after transplantation. According to the histological types and grades, 28 evaluated donors (8.2%) were suitable for transplantation. The histological types were: thyroid carcinoma (n = 3); prostate carcinoma (n = 8), renal clear cell carcinoma (n = 7), oncocytoma (n = 1), meningiomas (n = 2), dermofibrosarcoma (n = 1); verrucous carcinoma of the vulva (n = 1), colon adenocarcinoma (n = 1), grade II astrocytoma (n = 1), adrenal gland tumor (n = 1), gastric GIST (n = 1), oligodendroglioma (n = 1). Forty-five organs were retrieved (22 livers, 19 kidneys, 3 hearts, and 1 pancreas) and transplanted into 44 recipients with 1 liver-kidney combined transplantation. Four recipients died due to causes not related to the tumor. No donor-transmitted tumor was detected among the recipients. Donation is absolutely not indicated in cases of tumors with high metastatic potential and high grades. Performing an accurate evaluation of the donor, taking into account the histological grade, currently can allow, organ retrieval and transplantation with an acceptable risk. © 2012 Published by Elsevier Inc

Propylthiouracil Quantification In Human Plasma By High-performance Liquid Chromatography Coupled With Electrospray Tandem Mass Spectrometry: Application In A Bioequivalence Study

A rapid, sensitive and specific method for quantifying propylthiouracil in human plasma using methylthiouracil as the internal standard (IS) is described. The analyte and the IS were extracted from plasma by liquid-liquid extraction using an organic solvent (ethyl acetate). The extracts were analyzed by high performance liquid chromatography coupled with electrospray tandem mass spectrometry (HPLC-MS/MS) in negative mode (ES-). Chromatography was performed using a Phenomenex Gemini C18 5μm analytical column (4.6mm×150mm i.d.) and a mobile phase consisting of methanol/water/acetonitrile (40/40/20, v/v/v)+0.1% of formic acid. For propylthiouracil and I.S., the optimized parameters of the declustering potential, collision energy and collision exit potential were -60 (V), -26 (eV) and -5 (V), respectively. The method had a chromatographic run time of 2.5min and a linear calibration curve over the range 20-5000ng/mL. The limit of quantification was 20ng/mL. The stability tests indicated no significant degradation. This HPLC-MS/MS procedure was used to assess the bioequivalence of two propylthiouracil 100mg tablet formulations in healthy volunteers of both sexes in fasted and fed state. The geometric mean and 90% confidence interval CI of Test/Reference percent ratios were, without and with food, respectively: 109.28% (103.63-115.25%) and 115.60% (109.03-122.58%) for Cmax, 103.31% (100.74-105.96%) and 103.40% (101.03-105.84) for AUClast. Conclusion: This method offers advantages over those previously reported, in terms of both a simple liquid-liquid extraction without clean-up procedures, as well as a faster run time (2.5min). The LOQ of 20ng/mL is well suited for pharmacokinetic studies. The assay performance results indicate that the method is precise and accurate enough for the routine determination of the propylthiouracil in human plasma. The test formulation with and without food was bioequivalent to reference formulation. Food administration increased the Tmax and decreased the bioavailability (Cmax and AUC). © 2014 Elsevier B.V.9691928Glinoer, D., Cooper, D.S., (2012) Curr. Opin. Endocrinol. Diabetes Obes., 19, pp. 402-407Zakrzewski, R., (2008) Arch. Pharm. Res., 31, pp. 1622-1630Wei, Y., Zhang, Z.J., Zhang, Y.T., Sun, Y.H., (2007) J. Chromatogr. B: Analyt. Technol. Biomed. Life Sci., 854, pp. 239-244Okuno, A., Taguchi, T., Inyaku, F., Yano, K., Suzuki, Y., (1983) Pediatr. Pharmacol., 3, pp. 43-47Ringhand, H.P., Ritschel, W.A., Meyer, M.C., Straughn, A.B., Cabana, B.E., (1983) J. Pharm. Sci., 72, pp. 1409-1412Giles, H.G., Roberts, E.A., Orrego, H., Sellers, E.M., (1981) J. Clin. Pharmacol., 21, pp. 466-471Clark, S.M., Saade, G.R., Snodgrass, W.R., Hankins, G.D., (2006) Ther. Drug. Monit., 28, pp. 477-483Rosseel, M.T., Lefebvre, R.A., (1990) J. Chromatogr., 16, pp. 247-251Zakrzewski, R., (2008) J. Pharm. Biomed. Anal., 10, pp. 145-159Abdul-Fattah, A.M., Bhargava, H.N., (2001) Drug Dev. Ind. Pharm., 27, pp. 831-835Batjoens, P., De Brabander, H.F., De Wasch, K., (1996) J. Chromatogr., 25, pp. 127-132Giles, H.G., Miller, R., Sellers, E.M., (1979) J. Pharm. Sci., 68 (11), pp. 1459-1460Cannell, G.R., Williams, J.P., Yap, A.S., Mortimer, R.H., (1991) J. Chromatogr., 564, pp. 310-314Moretti, G., Betto, P., Cammarata, P., Fracassi, F., Giambenedetti, M., Borghese, A., (1993) J. Chromatogr., 616, pp. 291-296Pinel, G., Bichon, E., Pouponneau, K., Maume, D., André, F., Le Bizec, B., (2005) J. Chromatogr. A, 1085, pp. 247-252Lõhmus, M., Kallaste, K., Le Bizec, B., (2009) J. Chromatogr. A, 1216 (46), pp. 8080-8089(2013) J. Am. Med. Assoc., 310, pp. 2191-2194. , World Medical Association(2003) Bioavailability and Bioequivalence Studies for Orally Administered Drug Products - General Considerations, , Food and Drug Administratio