Biomedical subjects

F Pinguet

Publications and source records attributed to F Pinguet.

At least 19 recordsLinked to original sources

PubMed2006

Stability of amphotericin B and nystatin in antifungal mouthrinses containing sodium hydrogen carbonate.

Amphotericin B and nystatin are two polyene antibiotics that are potent antifungal agents. These drugs are active against most pathogenic fungi like Aspergillus and Candida. Mouthrinses containing these drugs are used for preventive and curative treatment of fungal infections like oral candidiasis, which can cause multiple diseases in cancer patients. Because there were no marketed antifungal mouthrinses available, their preparations were performed at the hospital and town pharmacies. To date, there are no data available on the stability of both these drugs in the form of mouthrinses. Therefore, each mouthrinse had to be prepared extemporaneously. The aim of this study was to investigate the stability of amphotericin B (Fungizone) and nystatin (Mycostatine) in the form of mouthrinses containing 1.4% sodium hydrogen carbonate. The stability of these solutions was tested at different temperatures (4-37 degrees C) with or without electric- or sunlight exposure and in two types of containers (glass and polypropylene) over a 15-day period. The admixtures were also monitored for colour change and pH. Amphotericin B and nystatin were quantified by high-performance liquid chromatography. At 4 degrees C, amphotericin B and nystatin were stable for 15 days in polypropylene. When stored in polypropylene at room temperature, with or without light protection, amphotericin B and nystatin were stable for 3 and 4 days, respectively.

Amphotericin B↗

PubMed2004

Simultaneous determination of dexamethasone and 6 beta-hydroxydexamethasone in urine using solid-phase extraction and liquid chromatography: applications to in vivo measurement of cytochrome P450 3A4 activity.

It has been demonstrated that the formation of the hydrophilic metabolites of dexamethasone, 6 alpha- and 6 beta-hydroxydexamethasone, correlated with cytochrome P450 (CYP) 3A4 enzyme levels. So, the 6 beta-hydroxydexamethasone/dexamethasone urinary ratio could be a specific marker for human CYP3A4 activity. We have developed a sensitive and specific high-performance liquid chromatographic method for the simultaneous quantification of urinary free dexamethasone and 6 beta-hydroxydexamethasone using 6 alpha-methylprednisolone as internal standard. This method involved a solid phase extraction of the three compounds from urine using Oasis HLB Waters cartridges with an elution solvent of ethyl acetate (2 ml) followed by diethyl ether (1 ml). Separation of the three analytes was achieved within 24 min using a reversed-phase Nova-Pak C(18) analytical column (4 microm, 300 mm x 3.9 mm i.d.). An ultraviolet detector operated at 245 nm was used with a linear response observed from 10 to 100 ng/ml for dexamethasone and from 25 to 1000 ng/ml for 6 beta-hydroxydexamethasone. Obtained from the method validation, inter-assay precision was below 15% and accuracy ranged from 95.7 to 110%. The extraction efficiency of the assay was approximately of 99% and was constant across the calibration range. The lower limit of quantitation was 10 ng/ml for dexamethasone and 25 ng/ml for 6 beta-hydroxydexamethasone; at these levels, precision was below 16% and accuracy was 99-109%. This method was applied to in vivo measure of the CYP3A4 activity.

Chromatography, Liquid↗

PubMed2001

Salivary and plasma pharmacokinetics of topotecan in patients with metastatic epithelial ovarian cancer.

The comparative saliva/plasma pharmacokinetics of topotecan were investigated in 13 patients with metastatic epithelial ovarian cancer receiving topotecan (30-min intravenous (i.v.) infusion) on a five consecutive day schedule every 3 weeks. During the first and the second courses of treatment, each patient underwent pharmacokinetic evaluation. Quantitation of the total topotecan (lactone plus carboxylate form) was assessed by a highly specific high-performance liquid chromatographic (HPLC) method. Large patient-to-patient variations in the plasma and saliva concentrations were observed. Plasma and saliva pharmacokinetics could be described using a biexponential pattern. From the saliva data, the half-life of the terminal part of the curve was 2.64 h, it was of the same order of magnitude as the topotecan elimination half-life determined from the plasma data, 3.18 h. Topotecan concentrations were higher in the saliva than in the plasma, the saliva/plasma concentration ratio averaged 2.31 and the ratio area under the parotid saliva (AUC(s)) over plasma (AUC(p)) concentration-time curve (AUC(s)/AUC(p)) averaged 2.11. For each individual, a significant relationship was found between topotecan concentrations in the saliva and in the plasma, the coefficients of correlation ranged from 0.75 to 0.92 according to the patient. Myelosuppression, especially granulocytopenia was the most frequent toxicity encountered during the trial. The percent decrease in the leucocyte count, absolute neutrophil count and platelet count were related to the AUCp/day using sigmoidal E(max) models. The high values of the Hill constant found reflect the very steep AUC-haematoxicity relationship observed. In most cases, abdominal pain occurred in patients presenting high saliva concentrations. One patient with high salivary concentrations (mean S/P ratio=4.60) had grade 1 mucositis. In conclusion, the concentration of topotecan in saliva appeared to be useful as an indirect, non-invasive estimation of the levels of topotecan in the plasma; thus, saliva concentrations could be a good predictor of the behaviour of topotecan in the body.

Adult↗

PubMed2001

Cytotoxicity of iridals, triterpenoids from Iris, on human tumor cell lines A2780 and K562.

Six different triterpenoids (known iridals) extracted from Iris germanica L. were purified and bioassayed on two cultured human tumor cell lines: A2780 and K562 (and for each one a drug-sensitive and a drug-resistant cell line). All of the tested iridals had an IC50 in the 0.1 to 5.3 microg/ml range. Some of them were shown to be more effective than doxorubicine. Toxicity of iridals on multi-drug resistance (MDR) expressing cell lines seemed to indicate that the effects of these triterpenoids are less affected by MDR than those of doxorubicine or taxol.

Antineoplastic Agents, Phytogenic↗

PubMed2001

Synthesis and in vitro cytotoxic evaluation of new derivatives of pyrido[1,2-a]benzimidazolic ring system: the pyrido[1',2':1,2]imidazo[4,5-h]quinazolines.

Access to the original series of pyrido[1',2':1,2]imidazo[4,5-h]quinazoline was developed from a 1,3-dicarbonyl unit with some "N-C-N" bisnucleophilic reagents and the derivatives obtained were evaluated for in vitro cytotoxic activities against HL60 and A2780 cells. All compounds exhibited cytotoxic activities on resistant cell lines (MDR+; HL60R and A2780R) with no resistance phenomena.

Animals↗

PubMed2000

High-performance liquid chromatographic determination of vinorelbine in human plasma and blood: application to a pharmacokinetic study.

A sensitive and specific high-performance liquid chromatographic method with fluorescence detection (excitation wavelength: 280 nm; emission wavelength: 360 nm) was developed and validated for the determination of vinorelbine in plasma and blood samples. The sample pretreatment procedure involved two liquid-liquid extraction steps. Vinblastine served as the internal standard. The system uses a Spherisorb cyano analytical column (250x4.6 mm I.D.) packed with 5 microm diameter particles as the stationary phase and a mobile phase of acetonitrile-80 mM ammonium acetate (50:50, v/v) adjusted to pH 2.5 with hydrochloric acid. The assay showed linearity from 1 to 100 ng/ml in plasma and from 2.5 to 100 ng/ml in blood. The limits of quantitation were 1 ng/ml and 2.5 ng/ml, respectively. Precision expressed as RSD was in the range 3.9 to 20% (limit of quantitation). Accuracy ranged from 92 to 120%. Extraction recoveries from plasma and blood averaged 101 and 75%, respectively. This method was used to follow the time course of the concentration of vinorelbine in human plasma and blood samples after a 10-min infusion period of 20 mg/m2 of this drug in patients with metastatic cancer.

Aged↗

PubMed2000

Population pharmacokinetics of topotecan: intraindividual variability in total drug.

The inter- and intraindividual variabilities in topotecan clearance (CL) were explored using a population pharmacokinetic approach. Total (lactone + hydroxy acid) topotecan plasma concentrations were obtained in 31 women with metastatic epithelial ovarian cancer treated by the 30-min intravenous infusion on 5 subsequent days. The data corresponding to three occasions (days 1 and 5 of cycle 1, and day 1 of cycle 2), were analyzed using the nonlinear mixed effect model program. A large interindividual variability was observed, with CL varying from 9.1 to 42.51 per hour (mean 21.0). Topotecan CL was related to serum creatinine level, and age. A close relationship was also observed between topotecan CL and creatinine clearance. Intraindividual variability both within cycle 1 and between the two first cycles was limited, with a mean variation of -2+/-17%, and + 5+/-20%, respectively. A limited sampling strategy using Bayesian estimation based on two samples (5 min before the end of the 30-min infusion, and 4 h after the end of infusion) was developed. The results of this study combine relationships between topotecan pharmacokinetic parameters and patient covariates that may be useful for a priori dose adjustment, and convenient sampling procedure that can be used for further studies and drug monitoring.

Aged↗

PubMed2000

A phase I and pharmacokinetic study of melphalan using a 24-hour continuous infusion in patients with advanced malignancies.

The objectives of the present study were to determine the following: (a) the maximum tolerated dose (MTD) of melphalan using a 24-h continuous infusion; (b) the clinical toxicity; and (c) the pharmacokinetic characteristics of melphalan at each dose level. Twenty-one patients with refractory solid tumors were enrolled in the study. Melphalan, packaged in 3% sodium chloride, was administered i.v. over a 24-h period. Patients were assigned to one of three escalating dose levels of melphalan: (a) 20 mg/m2 (n = 5); (b) 30 mg/m2 (n = 7); and (c) 40 mg/m2 (n = 6). Each patient underwent pharmacokinetic evaluation during the first cycle of treatment. Melphalan concentrations in plasma were determined by high-performance liquid chromatography. Toxicity was evaluated after each course of chemotherapy. All of the patients were assessable for toxicity and pharmacokinetics, and 20 patients were assessable for response analysis. A total of 50 courses of melphalan was studied. The MTD was 30 mg/m2. The dose-limiting toxicity was neutropenia and thrombocytopenia. Hematotoxicity was reversible (nadir, 14-15 days; recovery, 3.5 and 12.5 days for 30 and 40 mg/m2, respectively), cumulative, and related to the administered dose and to the history of previous therapy. There were six episodes of neutropenic sepsis. Individual pharmacokinetic parameters were estimated using a Bayesian approach and linear elimination kinetics. Data were compatible with a one-compartment model. Relationships have been found between the area under the plasma concentration-time curve and doses and between Css and doses. Moreover, clearance, t1/2 elimination, and volume of distribution did not change statistically with dose, which suggests linear kinetics. Two partial responses were observed in patients with ovarian carcinoma or adenocarcinoma of unknown primary origin, and another patient had stabilization disease. In conclusion, melphalan MTD was determined to be 30 mg/m2 when administered as a 24-h infusion. Hematological toxicity was the dose-limiting toxicity. The most important nonhematological toxicity encountered was nausea and vomiting. The recommended dose for Phase II studies was 30 mg/m2.

Adolescent↗

PubMed2000

Bayesian estimate of vinorelbine pharmacokinetic parameters in elderly patients with advanced metastatic cancer.

The objective of the present study was to determine the pharmacokinetic profile of vinorelbine in patients 65 years or older with metastatic cancer in progression. Twelve patients were enrolled in this study. Vinorelbine was administered by a 10-min continuous infusion at a dose of 20-30 mg/m2 through a central venous catheter. Chemotherapy was repeated weekly. A total of 46 courses of vinorelbine was studied. Each patient underwent pharmacokinetic evaluation during the first cycle of treatment. Toxicity evaluation was carried out before each course of chemotherapy. Plasma vinorelbine determinations were performed by high-performance liquid chromatography with spectrofluorometric detection. A Bayesian estimation of individual pharmacokinetic parameters was carried out using the nonlinear mixed-effect modeling approach as implemented in the NONMEM computer program. An open three-compartment pharmacokinetic model with a zero order input rate was used to describe the kinetics of vinorelbine. Area under the plasma-concentration time curve (AUC) normalized to a 30 mg/m2 administered dose averaged 0.89 mg/liter x h (coefficient of variation = 23.7%). The total plasma clearance averaged 0.93 liter/h/kg (0.61-1.83 liter/h/kg; coefficient of variation = 38.6%). The elimination half-life was 38.1 +/- 5.8 h. A high correlation was found between patient age and total clearance (r = -0.8; P < 0.001). The main hematological toxicity observed was anemia in 11 patients. Neutropenia occurred in 50% of patients. Significant correlations were found between AUC and the decrease in the hemoglobin level (r = 0.60) and between AUC and the decrease in the neutrophil count (r = 0.66). Thrombocytopenia was observed in only one patient. In conclusion, the age-related decrease in clearance found in this study supports the design of a Phase I study of vinorelbine in patients older than 65 years or perhaps 70 years.

Age Factors↗

PubMed1999

Methyl-beta-cyclodextrin and doxorubicin pharmacokinetics and tissue concentrations following bolus injection of these drugs alone or together in the rabbit.

The purpose of this work was to determine the pharmacokinetics and the tissue concentrations of methyl-beta-cyclodextrin (MEBCD) and doxorubicin (DOX) in rabbits following administration of MEBCD and DOX, alone or in combination. MEBCD (200 mg/kg) and DOX (1 mg/kg) were intravenously injected to white New Zealand rabbits and blood samples were obtained over a 48-h period after administration. After this period, administration was repeated and animals were killed 1, 2 or 4 h after injection. Heart, liver and kidney were then removed. MEBCD and DOX analysis in plasma and tissues was performed using two HPLC methods with fluorimetric detection. MEBCD pharmacokinetic profile was consistent with a two-compartment model (t1/2 alpha: 30 min; t1/2 beta: 7 h). Co-administration with DOX did not modify the main pharmacokinetic parameters of MEBCD. However, C5 min, t1/2 alpha, t1/2 beta and AUCinfinity were decreased by the co-administration of DOX with MEBCD compared to DOX alone. Assays of excised tissues showed that DOX enhanced the cardiac, renal and hepatic concentrations of MEBCD. On the other hand, MEBCD did not alter the cardiac distribution of DOX, while renal and hepatic distribution profiles were modified. In this study, the pharmacokinetic parameters of MEBCD injected intravenously were determined for the first time. DOX did not enhance MEBCD pharmacokinetic profile but MEBCD reduced the distribution half-life of DOX. Tissue determination showed that MEBCD did not enhanced the cardiac accumulation of DOX, which is auspicious for further in vivo experiments using the co-administration of DOX and MEBCD.

Animals↗

PubMed1999

Circadian rhythm of 5-fluorouracil population pharmacokinetics in patients with metastatic colorectal cancer.

PURPOSE: The purpose of this work was to estimate the population pharmacokinetic parameters of 5-fluorouracil (5-FU) in patients with advanced colorectal cancer using circadian change kinetics. METHODS: Eighty-five patients (32 females, 53 males) were enrolled onto this study. All patients received folinic acid (200 mg/m(2)) by intravenous infusion over 2 h followed by a 5-FU loading dose (400 mg/m(2)) and then continuous infusion (600 mg/m(2)) for 22 h. This whole regimen was repeated on day 2 and was given on a 14-day cycle. Plasma 5-FU determinations were performed by high-performance liquid chromatography with ultraviolet absorbance detection. Pharmacokinetic analyses were performed using the NONMEM computer program through the Visual-NM graphical interface. An open one-compartment pharmacokinetic model with zero-order input rate was used to describe the kinetics of 5-FU; moreover, circadian time-dependent changes in 5-FU concentrations were taken into account in the model. The circadian model was defined as the sum of two cyclic components; the amplitude of the first cyclic component (over 24 h) was about 30% of the average clearance and the amplitude of the second cyclic component (over 12 h) was about 50% of the amplitude of the first component. The acrophase (peak) times of the first and the second periodic component were 04 h 12 m and 00 h 25 m, respectively. The potential sources of variability on the population parameters (65 patients) were investigated using patient's sex, body area, age, body weight, height, liver enzymes and serum creatinine as covariables. RESULTS: Only the estimated clearance circadian changes were different for the two sexes. The population parameter estimates of mean clearance (CL(mean)) and initial volume of distribution (V), were as follows: the male subgroup showed a CL(mean) value twice larger (125 l/h) than the value observed in the female subgroup (65 l/h), and V = 21 l. A validation group of 20 additional patients was used to evaluate the predictive performances of the population parameters. The individual pharmacokinetic parameters were computed by means of a Bayesian fitting procedure. From the resulting individualized parameter values, concentrations of 5-FU in the plasma were calculated. To evaluate the performance of the Bayesian estimation, the experimental concentrations were compared with the predicted ones. CONCLUSION: In conclusion, a chronomodulated delivery schedule of 5-FU should be performed, using a perfusion rate inversely proportional to the circadian variations of clearance in order to maintain stable 5-FU plasma levels. Such a treatment schedule may result in increased effectiveness of the treatment and decreased occurrence of drug-associated side-effects. The present study develops a complete procedure to efficiently estimate 5-FU clearance in order to optimize dosage regimens in individual patients.

Aged↗

PubMed1999

Plasma and salivary pharmacokinetics of 5-fluorouracil (5-FU) in patients with metastatic colorectal cancer receiving 5-FU bolus plus continuous infusion with high-dose folinic acid.

The comparative saliva/plasma pharmacokinetics of 5-fluorouracil (5-FU) were investigated in 21 patients with metastatic colorectal cancer receiving high-dose folinic acid (LV (leucovorin) 200 mg/m2) followed by 5-FU bolus (400 mg/m2) and continuous infusion (600, 750, 900 or 1200 mg/m2) on days 1 and 2. Quantitation of unchanged drug was assessed by a highly specific high-performance liquid chromatographic method. Large patient-to-patient variations in plasma and saliva 5-FU concentrations were observed. Saliva pharmacokinetics could be described using a bi-exponential pattern. The half-life of the rapid phase averaged 8.0 min, and was of the same order of magnitude as the 5-FU elimination half-life determined from plasma data. The half-life of the terminal part of the curve averaged 8 h; such decrease in salivary concentrations could be due to changes in salivary gland function caused by 5-FU, which results in reduced salivary flow rate. Between individual 5-FU concentrations in parotid saliva and plasma a statistically significant straight line could be fitted with a coefficient of correlation of 0.675. Moreover, the risk of developing 5-FU-related mucositis was significantly linked to 5-FU salivary exposure. Diarrhoea was the most frequent toxicity encountered during the trial.

Adult↗

PubMed1999

Influence of the schedule of exposure on the cytotoxic effect of melphalan on human 8226 and A2780 cells.

Melphalan was investigated for antitumoral activity using two schedules of exposure (solid versus sequential exposure) in two human cancer cell lines (8226 and A2780). Sequential exposure of melphalan was more effective than solid exposure at the same total dose. The IC50 values averaged 8.2 (solid exposure) and 0.16 microgram/ml (sequential exposure) for 8226 cells (myeloma), and 7.5 (solid) and 0.53 microgram/ml (sequential) for A2780 cells (ovarian carcinoma). Intracellular melphalan accumulation, determined by high-performance liquid chromatography, showed that the area under the intracellular concentration of melphalan versus time curve (between 0 and 30 h) was significantly higher after sequential doses (9.4 micrograms/ml x h) than after solid dose (6.6 micrograms/ml x h). Moreover, intracellular/extracellular concentration ratios indicated that melphalan uptake followed a passive transport system. The increase of both duration of exposure (11 h after solid exposure versus 20 h after sequential doses) and intracellular concentrations 5-6 h after the beginning of the experiment (approximately 3 times higher after sequential doses) indicate sequential administration of melphalan could be more effective than solid exposure.

Adenocarcinoma↗

PubMed1999

Combination paclitaxel and vinorelbine therapy: in vitro cytotoxic interactions and dose-escalation study in breast cancer patients previously exposed to anthracyclines.

The objectives of the present study were first to analyse the in vitro cytotoxic interactions between paclitaxel and vinorelbine in order to approach the optimal clinical scheduling in cancer patients, and second to determine the maximum-tolerated doses of this combination without haematopoietic growth factor in breast cancer patients previously exposed to anthracyclines. The in vitro cytotoxicity of paclitaxel and vinorelbine alone, in combination and in sequence, was evaluated against the established human doxorubicin-resistant MCF7 (MCF7-R) breast carcinoma cell line using the standard isobologram methodology. Regarding the simultaneous exposure to vinorelbine and paclitaxel, the combined data points fell mainly on the left side of the envelope of additivity suggesting a synergistic interaction. Conversely the representative isobologram of MCF7-R cells for sequential exposure to vinorelbine followed by paclitaxel or paclitaxel followed by vinorelbine indicated antagonism. These results prompted us to perform a trial of paclitaxel/vinorelbine combination using the administration of these drugs on the same day directly one after the other. The dose-escalation trial included 20 women with metastatic breast cancer who were treated by paclitaxel every 3 weeks (135 mg/m2 starting dose) with 20 mg/m2 steps in subsequent cohorts of patients and vinorelbine (30 mg/m2 fixed dose). Patients were treated every 21 days. A total of 91 courses of therapy were administered to patients at three dose levels. Neutropenic fever was the dose-limiting toxicity at level 3 (paclitaxel 175 mg/m2). Other significant toxicities included sensory neuropathy, myalgias and fatigue. We conclude that paclitaxel 155 mg/m2 and vinorelbine 30 mg/m2 administered directly one after the other on the same day, every 21 days, are the doses recommended for further study.

Adult↗

PubMed1999

Synthesis and cytotoxicity of novel pyrido[1,2-e]purines on multidrug resistant human MCF7 cells.

The anticancer activity of 4-methylaminopyridol[1,2-e]purine 6a, 4-(piperidin-1-yl)pyrido[1,2-e]purine 7a and their 7-methyl derivatives 6b, 7b was investigated against the human MCF7 cancer cell line in vitro. The sensitive cell line showed a range of sensitivities to 6a, 6b, 7a, 7b (IC50: 1.6 to 7.2 x 10(-4) M) and sensitivity to doxorubicin (IC50: 7.5 x 10(-7) M). A resistant cell line with the multidrug resistant phenotype was sensitive to these derivatives (IC50: 1.8 to 6.7 x 10(-4) M), doxorubicin (IC50: 5 x 10(-5) M) and drug activity seems to be not affected by MDR resistance. Our data show that 6a, 6b, 7a and 7b appear to exert a low cytotoxicity on sensitive and MDR resistant MCF7 human cancer cell lines.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1998

In vitro modulation of doxorubicin and docetaxel antitumoral activity by methyl-beta-cyclodextrin.

Methyl-beta-cyclodextrin (MEBCD) was investigated for its effect on the antitumoral activity of various antineoplastic agents (doxorubicin (DOX), docetaxel (DXL), 5-fluorouracil (5-FU) and cisplatin (CDDP)) in three different human parental sensitive cancer cell lines (K562 S, MCF7 S and A2780 S) and their multidrug resistant variant sublines (K562 R, MCF7 R and A2780 R). At non-cytotoxic concentrations, MEBCD was able to increase significantly DOX and DXL cytotoxic activity in all the cell lines tested. The sensitisation ratios (IC50 drug control/IC50 drug-MEBCD treated) ranged from 3l1 to 14.3. Moreover, intracellular DOX accumulation, determined by high-performance liquid chromatography, was also increased when cells were treated with MEBCD combined with DOX (approximately 2-3 fold). The effects of MEBCD in resistant sublines were greater than in their parental sensitive cell lines. Other experiments demonstrated that the action of the MEBCD was independent of DOX. These data provided a basis for the potential therapeutic application of MEBCD in cancer therapy.

Antibiotics, Antineoplastic↗

PubMed1998

Antiproliferative effect of methyl-beta-cyclodextrin in vitro and in human tumour xenografted athymic nude mice.

The anti-tumour activity of methyl-beta-cyclodextrin (MEBCD), a cyclic oligosaccharide known for its interaction with the plasma membrane, was investigated in vitro and in vivo and compared with that of doxorubicin (DOX) in the human tumour models MCF7 breast carcinoma and A2780 ovarian carcinoma. In vitro proliferation was assessed using the MTT assay. In vivo studies were carried out using xenografted Swiss nude mice injected weekly i.p. with MEBCD at 300 or 800 mg kg(-1) or DOX at 2 mg kg(-1), during 2 months. Under these conditions, MEBCD was active against MCF7 and A2780 cell lines and tumour xenografts. For each tumour model, the tumoral volume of the xenografted mice treated with MEBCD was at least twofold reduced compared with the control group. In the MCF7 model, MEBCD (800 mg kg(-1)) was more active than DOX (2 mg kg(-1)). After 56 days of treatment with MEBCD, no toxicologically meaningful differences were observed in macroscopic and microscopic parameters compared with controls. The accumulation of MEBCD in normal and tumour tissues was also assessed using a chromatographic method. Results indicated that after a single injection of MEBCD, tumour, liver and kidneys accumulated the highest concentrations of MEBCD. These results provided a basis for the potential therapeutic application of MEBCD in cancer therapy.

Adenocarcinoma↗

PubMed1998

Regioselective synthesis of pyrazolo[4,5-g]pyrido[1,2-a]benzimidazoles: cytotoxic derivatives of pyrido[1,2-a]benzimidazolic ring system.

N-1 and N-2 substituted pyrazolo[4,5-g]pyrido[1,2-a]benzimidazoles were prepared regioselectively, and cytotoxicities evaluated in vitro against K562 and HL60 cells. All compounds displayed weaker activity than doxorubicin against sensitive lines, but showed the same activity against resistant cell lines (multidrug resistance+, (MDR+); K562R and HL60R) indicating no resistance phenomena.

Antibiotics, Antineoplastic↗