Gemicitabine (2',2'-difluorodesoxycitidine) is a relatively new medicinal product from the group of anti-metabolites used as the first line therapy of pancreatic cancer, non-pulmonary cancer, and breast cancer. However, analysis of its toxicity spectrum revealed a large number of adverse events associated with the clinical application of this product. This fact is ascribed to the narrow range of therapeutic usages of this cytostatic preparation (from 25 mg/kg to 27 mg/kg). This paper is designed to summarize the available data on hematological, gastrointestinal, pulmonary, and cardiotoxicity of gemcitabine. They may be useful for the improvement of control over gemcitabine toxicity, correction of its dosage regime, and efficacious prevention of the most serious side effects.

Methotrexate is one of the most effective and widely used cytostatic drugs. However as all antineoplastic drugs it has very low therapeutic index and high toxicity. Kinetic parameters (rate constants, half-times of restoration and extreme values of concentrations at the beginning of methotrexate infusion) were estimated for biochemical markers It is the method of the quantitative assessment of the drug toxicity. The biokinetic findings allow to set an optimum time interval between infusions of methotrexate for minimization of toxicity at therapeutic efficacy keeping of the antineoplastic drug.

An analytical procedure has been developed for determining gemcitabine, the new drug with a broad spectrum of antitumor activity, in the human plasma. The sample preparation for the drag assay involves the precipitation of plasma proteins with a mixture of acetonitrile and methanol (9:1), followed by the acidification with glacial acetic acid. The resulting supernatant is evaporated to dryness at 42°C under vacuum and the residue is dissolved in a mobile phase consisting of acetate buffer (pH 5.0) and acetonitrile (97.5:2.5). Then, HPLC was carried out using reverse-phase column eluted under isocratic conditions. The UV detection of gemcitabine is performed at 282 nm. The limit of quantitation for gemcitabine was 1 μg/ml. This procedure can be used to obtain pharmacokinetic data for gemcitabine in patients with pancreatic cancer treated according to a modified long-term intravenous infusion protocol.

A method for estimating the antitumor agent gemcitabine in plasma by isocratic HPLC was developed. Sample preparation consisted of precipitating proteins with a mixture of acetonitrile and methanol (9:1) with subsequent acidification of the extract with glacial acetic acid. Supernatants were then evaporated to dryness in a rotary vacuum evaporator at 42°C. The dry residue was dissolved in the mobile phase, which consisted of a mixture of acetate buffer pH 5.0 and acetonitrile (97.5:2.5). UV detection of gemcitabine was performed at 282 nm. The detection limit for this compound was 1 µg/ml. This method can be used to study the pharmacokinetic characteristics of the agent within the frameworks of the protocol “Studies of dose-dependent regimes of long-term infusions of gemcitabine in patients with local and disseminated pancreas cancer.”

Presented the case of complex examination of a patient with pancreatic cancer using a bioimpedance method for assessing the nutritional status before and aft er surgical treatment. Provided the literature data related to this problem. Th e presented clinical case demonstrates the features of correction of the nutritional status of a patient with conditionally resectable pancreatic cancer in conditions of cholestasis, severe external pancreatic insuffi ciency and pancreatogenic diabetes mellitus on the background of constitutional obesity.

Methotrexate is a most common antitumor therapy. The drug is mainly excreted in urine. Most serious and dangerous complications of methotrexate therapy include hematology toxicity, mucosites and nephrotoxicity. The longer elevated blood methotrexate levels are maintained, the higher the risk and severity of toxicity. Extracorporal methotrexate elimination is rather difficult. Hemodialysis and peritoneal dialysis are low effective; elimination by hemosorption is unpredictable. High flux hemodialysis is rather effective though its use is limited by the need in special equipment. We have found hemofiltration to ensure effective and predictable extracorporal methotrexate removal. Coefficient of methotrexate sieving through F-80S standard hemofilter membrane was calculated during two consecutive hemofiltration treatments in a patient (0.65-0.66). Standard hemofiltration with vascular access through a perfusion catheter ensured clearance of methotrexate compatible with normal renal clearance.

Dissolution profiles of cyclosporin A available in the form of soft gelatin capsules from four manufacturers were studied and characterized by the similarity and dissimilarity coefficients. No similarity was found between the dissolution profiles of the original preparation and three generics, although the integral dissolution indices of all preparations at the end point (60 min) were quite comparable. Therefore, determination of the dissolution index alone does not provide adequate evaluation of the bioequivalence of generics.

This article deals with the stability investigation of capsule formulations of cyclosporine A, which is the first line immunosuppressive agent in bone marrow and solid organ transplantations. The quality control of cyclosporine A preparations was carried out by estimation of «Assay» and «Related substances» criteria. 60-minutes dissolution profiles of cyclosporine A in soft gelatine capsules were investigated. It has been shown that cyclosporine A content after expiration dating period has decreased. At the same time related substances total content as well as that of individual identified related substances (cyclosporine H, dihydrocyclosporine A, cyclosporine V, cyclosporine D, isocyclosporine A) has increased. The decrease of dissolution index and changes in dissolution profiles of cyclosporine A in investigated preparations after expiration dating period have been shown. By the example of cyclosporine A capsule formulations, the advisability of the study of active substance release along with «Assay» and «Related substances» criteria have been demonstrated.

Изучение профилей растворения циклоспорина А выявило различный характер его высвобождения из мягких желатиновых капсул (МЖК) разных производителей. Анализ полученных профилей с использованием коэффициентов подобия и различия показал отсутствие подобия между кинетикой высвобождения циклоспорина А из оригинального препарата и препаратов-дженериков. Тем не менее, к 60 минуте показатели растворения всех лекарственных форм достигали сопоставимых величин. Полученные результаты являются дополнительным подтверждением того, что определение только показателя растворения недостаточно для полной оценки эквивалентности препаратов-дженериков.

EEG was performed in 25 children with lymphoblastic tumors before and after the first chemotherapy course by BFM schedule to assess functional state of the central nervous system during chemotherapeutic treatment. Levels of N-acetylneuraminic acid, medium weight molecules, malonic dialdehyde, vitamins A and E, vanyllylmandelic acid were measured in 8 cases. Unlike healthy children the patients with lymphoblastic tumors presented EEG signs of central nervous system injury as changes in hypothalamuspituitary system due to marked endogeneous intoxication and decreased antioxidant potential. These changes increased after the first chemotherapy course and manifested themselves as enhanced -activity in frontocentral cerebral cortex and decreased 2-activity. The increased electrophysiological and biochemical parameters after chemotherapy suggested further deterioration of toxic injury of the brain.

The distribution of epidermal growth factor receptors (EGFR) and receptors for steroid hormones--androgens (RA), estrogens (RE) and glucocorticoids (RG) was studied in malignant (MT) and benign (BT) tumors in children. The distribution and mean levels of some receptors in normal tissues were statistically different from those in MT and BT. The absence of RA and the high levels of RE > 20 fmol/mg protein and RG > 50 fmol/mg protein were typical of MT whereas BT might be characterized by the high levels of EGFR > 300 fmol/mg protein. In MT with and without metastases, the following parameters were significantly different (p < 0.001): RG = 81 and 18 fmol/mg, respectively, and EGFR = 160 and 58 fmol/mg protein, respectively. The most informative parameters for distinguishing BT and MT appeared to be RA (0.086 dit), RE (0.043 dit) and EGFR (0.037 dit). The most sensitive parameter for MT was RG, which, however, is least specific; RA is most specific (75%). The optimal amount of three parameters: RA + RE + EGFR (88.4%) is most exact for differential diagnosis.