The absorption, disposition, biotransformation and excretion of the nonsteroidal anti-inflammatory drug pirazolac were investigated in 6 volunteers (3 males, 3 females, age 50 greater than years) after intravenous and oral administration of 50 mg 14C-pirazolac as an aqueous solution of the sodium salt. Pirazolac was very rapidly and completely absorbed and bioavailable when orally administered in a dose of 50 mg in solution. Maximum pirazolac levels in plasma of 6 micrograms/ml (30% of dose in total plasma volume) were already reached after approx. 20 minutes. No metabolites were detectable in the plasma. Pirazolac was eliminated from the plasma in two phases with half-lives of 3 hours and 16 hours, respectively, regardless of administration route. After intravenous and oral administration approximately 80% of the dose was excreted with the urine and approximately 15% with the feces within 7 days, indicating a complete excretion of 14C-radioactivity. In urine, approximately 10% of the dose was identified as unchanged pirazolac and 70% as pirazolac ester glucuronide.
The blood plasma levels of 5-fluorouracil (5FU) after i.v. administration have been determined without and under the influence of 1, 5 or 9 million units (MU) preadministered interferon (IFN) in patients with gastrointestinal carcinoma. The co-administration of 9 MU IFN causes a doubled increase of the 5FU serum concentrations combined with a statistically significant change of the pharmacokinetics of 5FU for c0, AUC, Vd and Cltot (P < 0.005). A similar effect with distinctly increased serum concentrations could be observed for the preadministration of 5 mU IFN whereby c0 and AUC were elevated significantly (P < 0.05), but not Vd, Cltot and cd. The preadministration of 1 MU IFN also leads to higher plasma levels, but no changes in the pharmacokinetics of 5FU could be calculated (P > 0.05). A linear correlation between the IFN dose and the pharmacokinetic parameters c0 (R = 0.958), AUC0-120 (R = 0.948), Vd (R = 0.941) and Cltot (R = 0.963) of 5FU could be found (P < 0.05), but not for the coefficient of distribution and t1/2el. The results indicate that the pharmacokinetics of 5FU might be influenced by the preadministered IFN dose.
From a health economy viewpoint PROSIT is superior to standard management. Early recognition of albuminuria and the introduction of a multifactorial treatment strategy make it possible to delay progression to terminal renal failure. In addition to its clinical benefits, prevention of dialysis and transplantation would reduce the annual savings of the health care system by several billion DM.
The serum and red blood cell (RBCs) disposition of epirubicin (EPR) after intravenous bolus injection without and with coadministered quinine (QUI) was investigated in patients undergoing a cyclic chemotherapy with EPR. QUI possesses a statistical significant influence on the EPR serum concentrations and, as a consequence, on the pharmacokinetic parameters for the initial distribution phase of EPR. Within the first 15 min after administration, EPR was distributed from the central compartiment distinctly faster in compare to the control, when QUI was preadministered (t1/2 = 6 min for the control group and t1/2 = 3 min with QUI; -46% , p < 0.05). Yet, in the beta-phase when drug-elimination predominates, no statistical significant influence of QUI in regard to EPR serum and RBC concentrations could be observed. Half-life of elimination was 9.5 h for the control group and 8.6 h for the QUI group (-10% ). The mean initial serum concentration (c0) was reduced significantly by QUI from 7359 ± 506 ng/ml to 4351 ± 1682 ng/ml (-42 % . p < 0.005). Furthermore. QUI caused a reduction of the serum bioavailability of EPR (expressed as AUC0-24-values) from 3404 ± 1008 ng/ml × h to 2359 ± 1073 ng/ml × h (-3 1 % , p < 0.05). Vd and Vdß were increased at about 90% and the mean total body clearance was accelerated from 45.3 to 148.7 ml/min, but due to the large standard deviations the calculated difference for these parameters was not statistically significant. In the observed time interval of 24 h, the red blood cell coefficient of distribution kRBC of EPR was lower if QUI was coadministered (kRBC = 1.25 ± 0.12 for the control group kRBC = 1.15 ± 0.13 under QUI; p < 0.04). The results point out that QUI induces an accelerated distribution of EPR from the blood into the tissue and that QUI additionally may have influence on the red-blood cell partitioning of EPR.
In this randomised prospective study we investigated whether treatment results of maximal androgen blockade (MAB) in patients with metastatic prostatic cancer can be further improved by additional Methotrexate therapy (MTX). A total number of 61 patients (stage T1 or '1"2) have been included and 31 were randomised to arm A receiving MAB, i.e. orchiectemy + flutamide (3x250 rag/d). In group B 30 patients were treated with MAB + 50 mg{m 2 MTX (once weekly for 4 months). 53 patients are evahiable for response criteria.
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