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Biomedical subjects

E Strocchi

Publications and source records attributed to E Strocchi.

At least 55 records · Page 3Linked to original sources
PubMed1988

HPLC analysis of doxorubicin, epirubicin and fluorescent metabolites in biological fluids.

A specific, sensitive and reliable HPLC method for the determination of doxorubicin (DX), epirubicin (epiDX) and their known fluorescent metabolites [doxorubicinol (DXol), epirubicinol (epiDXol) 7-deoxy-adriamycinone (metabolite C), adriamycinone (metabolite D), 7-deoxy-13-dihydro-adriamycinone (metabolite E), 13-dihydro-adriamycinone (metabolite F), 4'-O-beta-D-glucuronyl-4'-epiDX (metabolite G) and 4'-O-beta-D-glucuronly 13-dihydro-4'-epiDX (metabolite H)] in biological fluids (human plasma, bile and urine) has been developed and tested. Plasma samples were solid-phase-extracted (C18-bonded silica cartridges). Urine and bile samples were injected directly after the addition of the internal standard and dilution with 0.3 M phosphoric acid. Complete separation of unchanged drugs and metabolites was achieved with a mobile phase consisting of 75.6% 10 mM KH2PO4 and 24.4% CH3CN (the pH of the solution was adjusted to 4.3 with 0.03 M H3PO4) at a flow rate of 1.5 ml/min. For the analyses we used a cyanopropyl chromatographic column (25 cm x 4.6 mm i.d.; particle size 5 micron) and fluorescence detection with excitation wavelength set at 470 nm and emission at 580 nm. Sensitivity was better than 0.3 ng/ml for all substances analysed. The mean absolute recovery of unchanged drugs and metabolites was between 88.3% (metabolite E) and 98.92% (metabolite G). Intra- and interassay precisions (plasma samples) were better than 10.6% and 13.0%.

Body Fluids↗
PubMed1988

Epirubicin and doxorubicin comparative metabolism and pharmacokinetics. A cross-over study.

The pharmacokinetics and metabolism of doxorubicin (DX) and epirubicin (epiDX) were investigated in eight cancer patients who received 60 mg/m2 of both drugs independently by intravenous (i.v.) bolus at 3-week intervals according to a balanced cross-over design. Unchanged DX and epiDX plasma levels followed a triexponential decay. Half-lives (t/2) of the three decay phases were longer for DX (t/2 alpha: 4.8 vs. 3 min; t/2 beta 2.57 h vs. 1.09 h; t/2 gamma 48.4 vs. 31.2 h). According to a model-independent analysis, the different plasma disposition kinetics of the two compounds appears to be related to a higher plasma clearance (PlCl) and to a lower mean residence time (MRT) of epiDX (PlCl: 75.0 l/h, range: 35.6-133.4 l/h; MRT: 31.6 h, range: 7.0-41.5 h;) compared to DX (PlCl: 56.8 l/h, range: 24.4-119.5; MRT: 45.6 h, range: 26.0-83.1 h). No statistically significant differences could be detected for the volume of distribution at steady state (Vss) (epiDX, 31.8 l/kg; DX, 33.3 l/kg). Metabolites common to both compounds were detected in plasma: the 13-dihydro derivatives doxorubicinol (DXol) and epirubicinol (epiDXol), together with minor amounts of four aglycones (7-deoxy adriamycinone, adriamycinone, 7-deoxy 13-dihydro adriamycinone, and 13-dihydro adriamycinone). Following epiDX administration, two additional major metabolites were detected: the glucuronic acid conjugates of epiDX (4'-O-beta-D-glucuronyl-4'-epiDX) and epiDXol (4'-O-beta-D-glucuronyl 13-dihydro-4'-epiDX). This additional detoxication route appears to account for the more efficient and faster elimination of epiDX than of DX. In the urine collected in the 6 days after treatment, 12.2% of the DX and 11.9% of the epiDX dose was excreted as unchanged drug and fluorescent metabolites. A comparable renal clearance was calculated for DX (4.7 l/h, range 1.4-7.0 l/h) and epiDX (4.4 l/h, range 1.7-7.0 l/h). One patient with hepatic metastases and abnormal bilirubin serum level had percutaneous biliary drainage because of extrahepatic obstruction. The elimination of both drugs was significantly impaired in this patient; nevertheless, elimination of epiDX was still more efficient and faster than that of DX (PlCl: 35.6 vs. 24.4 l/h; MRT: 39.0 vs. 83.1 h; t/2 gamma: 47 vs. 74 h). This patient's biliary excretion accounted for 35.4% of the epiDX dose and 18.2% of the DX dose.

Chromatography, High Pressure Liquid↗
PubMed1988

Characterization of a Na+/K+-ATPase inhibitor from human plasma: preliminary data.

The role of an endogenous sodium pump inhibitor in the pathogenesis of hypertension has been reported in several papers. Unfortunately, because of the unknown structure and lack of biochemical characterization, some discrepancies have arisen. In this study we report a method to obtain extracts from human plasma that are able to inhibit Na+/K+-ATPase in vitro. Preliminary characterization was carried out, which showed that the extracts are able to inhibit Na+/K+-ATPase, pNPPase, and [3H]ouabain binding to red blood cells. The enzyme inhibition is not due to vanadate, FFA, or bivalent cations, and it seems to be reversible, dose-dependent, and largely prevented in E1 conformation of the enzyme. These results seem to support the hypothesis that human plasma contains a sodium pump inhibitor with many characteristics of a "ouabainlike" compound.

Blood Chemical Analysis↗
PubMed1987

Medroxyprogesterone acetate plasma pharmacokinetics after intravenous administration in rabbits.

Medroxyprogesterone acetate (MAP) plasma pharmacokinetics was followed up in a total of 30 New Zealand rabbits after i.v. administration (0.1, 0.5, and 1.0 mg/kg) of either an aqueous suspension or a homogeneous solution of the drug in dimethylsulphoxide (DMSO). A well-defined triphasic decay of MAP plasma levels was noticeable in the animals treated with DMSO solutions. A delayed concentration peak was often present when aqueous suspensions were used, so if is not feasible to fit the experiment with simple polyexponential equations. Model-independent pharmacokinetic analysis (statistical moment theory) revealed a significant dependence of plasma clearance and mean residence time on the dose administered in both conditions.

Animals↗
PubMed1987

Ciclosporin A: correlation of blood levels with acute graft-versus-host disease after bone marrow transplantation.

Thirty patients undergoing allogeneic bone marrow transplantation (BMT) for hematologic malignancies received ciclosporin A (CS-A) as prophylaxis of graft-versus-host disease (GVHD). CS-A trough levels were determined in whole blood by radioimmunoassay (RIA); results were not used to adjust the CS-A dosage. Neither the dose of CS-A administered nor the CS-A concentration and fluctuation of blood levels during the first 15 days after BMT correlated with acute GVHD. Conversely in the 13 patients with acute GVHD, CS-A concentrations in the 10 days prior to the onset of the disease were increasingly lower with increasing severity of GVHD. Moreover, patients without GVHD had higher CS-A concentrations in a matched period of time. Upon withdrawal of CS-A treatment, 7 patients developed GVHD. There was no possibility to predict who would do so, but the analysis of CS-A disappearance profiles indicates that effective CS-A concentrations might be lower during long-term treatment than the concentrations required early after transplant. Despite these relationships, CS-A concentration is of little predictive value in the individual patient because of the considerable overlap among patients.

Acute Disease↗
PubMed1987

The metabolic effects of enalapril.

The metabolic effects of Enalapril (EN) were compared in a cross over study with those of Propranolol (PPL). Long term treatment with the ACEI did not modify the lipid and glucose profile and increased urate excretion, while PPL increased triglycerides and decreased urate clearance.

Adult↗
PubMed1986

Biliary excretion and pharmacokinetics of 4'epidoxorubicin (epirubicin) in advanced cancer patients.

Plasma pharmacokinetics and biliary and urinary excretion of the new doxorubicin analogue, epirubicin, have been studied in three patients with extrahepatic obstruction and percutaneous biliary drainage. At variance with the reported observations concerning doxorubicin metabolism, conjugation of epirubicin and 13-dihydroepirubicin with glucuronic acid takes place, and corresponding amounts of 4'-o-beta-D-glucuronyl-4'-epidoxorubicin and 4'-o-beta-D-glucuronyl-13-dihydro-4'-epidoxorubicin can be found in the bile and urine. The total amount of unaltered drug and metabolites excreted in the bile in the first 4 days after treatment accounts for the 37%, 27%, and 40% of the administered dose; urinary excretion accounts for 19%, 16%, and 26%. Biliary clearance of epiDX (32.5, 8.1 and 21.6 l/h) is higher than renal clearance (15.2, 3.3 and 9.41 l/h). The relevance of the biliary disposition of epirubicin suggest prudent dose reduction in patients with impaired biliary drainage.

Bile↗
PubMed1986

Low dose oral administration of 4-demethoxydaunorubicin (idarubicin) in advanced cancer patients. A pharmacokinetic study.

Data relating to 4-demethoxydaunorubicin (DMDR) pharmacokinetics after oral administration (10-15 mg/m2 per day for 3 days) were collected in a total of 12 patients with advanced breast cancer and melanoma. Drug absorption took place in the first 2-4 h after administration. Plasma levels of the reduced metabolite DMDRol were higher than those of the parent compound: Peak levels were 4-10 ng/ml for DMDR and 15-40 ng/ml for DMDRol. The dose-corrected area under the time-concentration curve (AUC) was consequently higher for DMDRol (12.3-74.7, mean 32.6 vs 2.4-7.4, mean 4.6 ng/ml.mg for DMDR). Apparent plasma terminal half-lives after the last dose administered were in the range of 13-36 (mean 23.7) h for DMDR and 30-81 (mean 58.9) h for DMDRol. Drug and the reduced metabolite accumulated in the blood cells; the ratio of AUC (blood) to AUC (plasma) was 1.40-3.75 (mean 2.80) for DMDR and 1.29-3.50 (mean 2.16) for DMDRol. The biliary excretion of the drug and of the fluorescent metabolites was studied in two additional patients with extrahepatic obstruction and percutaneous biliary drainage. In the first 7 days of therapy, biliary excretion (DMDR + DMDRol) accounted for 3.7%-4% of the administered dose. In contrast to our observations with doxorubicin and epirubicin, urinary excretion seems very likely to be more important for this drug than biliary excretion. In these patients urinary excretions were 2.2, 2.9 times (for DMDR) and 1.2, 3.4 times (for DMDRol) the biliary excretion.

Administration, Oral↗
PubMed1986

Intrahepatic arterial administration of 4'epidoxorubicin (epirubicin) in advanced cancer patients. A pharmacokinetic study.

Epirubicin (epiDX) pharmacokinetics was followed in 10 advanced cancer patients with hepatic metastases from colorectal carcinoma or primary liver tumor after single bolus administration (20-40 mg) in the hepatic artery, through a surgically implanted catheter and subcutaneous access port. EpiDX plasma and whole blood concentrations follow a triphasic decay qualitatively similar to that observed after IV administration. Blood levels are consistently higher than plasma levels. Plasma clearance (nine patients, mean: 93.4 l/hr; range: 69.3-129.5 l/hr) is higher than the corresponding parameter determined in patients with hepatic metastases after intravenous therapy. The remaining patient is characterised by an abnormally low plasma clearance (13.6 l/hr), due to a hepato-pulmonary shunt. The subjects in this study were exposed to very low drug concentrations, and therefore experienced no relevant adverse side-effects.

Aged↗
PubMed1986

MPA at high doses in advanced breast cancer: a statistical evaluation.

A computerized, retrospective analysis of clinical and pharmacokinetic data relative to 380 cancer patients under medroxyprogesterone acetate (MPA) therapy has been carried out. A bioavailability:objective- response correlation was found only for mammary cancer patients with visceral metastases and a pain-control effect was observed in advanced cancer patients when MPA plasma levels were higher than 150-200 ng/ml. Discriminant analysis of the known prognostic factors for breast cancer indicates that receptorial status, site of predominant metastases, basal alkaline phosphatase and free interval are good predictors for possible clinical response, while the behavior of prolactin and previous treatments are predictors for non-response. There is no improvement in the efficacy of prediction in combining more than one prognostic factor.

Administration, Oral↗
PubMed1986

Medroxyprogesterone acetate plasma levels after a single oral administration of two drug formulations.

A comparison has been made between the absorption of oral medroxyprogesterone acetate (MPA) in an aqueous suspension preparation and in syrup form. Plasma drug profiles were measured after a single administration of the two formulations in 17 advanced cancer patients. On average the standard form (aqueous suspension) gave peak levels which were lower than the syrup mixture. However, the wide intersubject spread in MPA plasma levels observed in both groups did not allow any statistical significance to be assigned to this difference.

Administration, Oral↗
PubMed1986

Phase II studies on weekly cisplatinum plus epirubicin or etoposide in the treatment of advanced non-small cell bronchogenic carcinoma.

Thirty-six patients with advanced non-small cell bronchogenic carcinoma were divided in 2 groups for treatment with two different platinum-based combination therapy regimens. All 16 patients who received the weekly administered combination of 10 mg/m2 cisplatin (CDDP) plus 10 mg/m2 epirubicin (4EPIDX) experienced no clinical response. Among the 20 patients who received the combination CDDP (10 mg/m2) plus etoposide (VP16, 60 mg/m2) weekly, 4 of them (20%) showed partial remission (PR). The side effects of both combinations were of mild grade. Further study is needed to verify the effectiveness of the weekly combination of CDDP and VP16 by comparing the above regimen with the "standard" intermittent doses.

Aged↗
PubMed1985

Medroxyprogesterone acetate (MAP) and tamoxifen (TMX) plasma levels after simultaneous treatment with 'low' TMX and 'high' MAP doses.

Plasma levels of medroxyprogesterone acetate (MAP), tamoxifen (TMX) and its major metabolites, 4-hydroxy TMX and desmethyl TMX, were determined in five patients with advanced breast cancer following simultaneous MAP (2,000 mg/day) and TMX (20 mg/day) oral therapy. The interindividual variance in MAP plasma levels was wide; the mean plasma levels of both drugs were nearly identical, despite the large difference in the administered doses.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1985

Medroxyprogesterone acetate bioavailability after high-dose intraperitoneal administration in advanced cancer.

Administration of medroxyprogesterone acetate IP in advanced cancer with peritoneal metastases and ascitic effusion generates considerably higher drug plasma levels than those observed after PO or IM treatment. Comparison of areas under the time-concentration curves (AUC) with reference to the three administration routes indicates that after oral administration only 0.2%-17.4% (mean 5.7%; SD 3.77; 40 patients) of the administered dose is absorbed; after IM treatment a daily absorption of 0.7%-7.7% (mean 2.5%; SD 1.66; 30 patients) of the administered dose per injection site was computed.

Antineoplastic Agents↗