[Research on the estradiol receptor in breast cancer].
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Animals↗
Biomedical subjects
G Zanolo
Publications and source records attributed to G Zanolo.
Gas chromatography-mass spectrometry determination of etodolac in human plasma following single epicutaneous administration.
A highly sensitive gas chromatographic-mass spectrometric method for the determination of etodolac acid, as methyl ester, in plasma was developed. The feasibility and specificity of the method was ascertained monitoring the concentration levels in plasma samples collected from 12 male healthy volunteers given epicutaneously 5 g of 10% etodolac gel formulation.
Adult↗
14C-NaVP and 14C-PEV repeated dose study in rat. Pharmacokinetic study in rats after repeated oral administrations of 14C-valproic acid sodium salt and 14C-valproic acid pivaloyl oxymethyl ester.
The absorption, excretion and tissue distribution of radioactivity after repeated oral equimolar doses of 14C-valproic acid sodium salt (NaVP) or 14C-valproic acid pivaloyl oxymethyl ester (PEV) was investigated in male rats treated once a day for 14 consecutive days. The 14th day plasma time-course of radioactivity after PEV administrations was characterised by a slow absorption rate with a delayed peak (tmax 2 h, Cmax 7.52 +/- 1.35 microg eq./ml), followed by a plateau lasting up to 8 h. After NaVP treatment, the main peak of radioactivity was observed 0.5 h after administration (Cmax 8.30 +/- 1.26 microg eq./ml) followed by a secondary peak due to biliary enterohepatic recycling. Starting from 4 h onwards, radioactivity levels after PEV treatment were higher than those after NaVP (AUCtau = 113.3 h.microg eq./ml after PEV vs 71.9 h.microg eq./ml after NaVP), but concentrations declined with similar terminal half-lives (52.8 h for PEV and 49.7 h for NaVP). Radioactivity recovered (0-432 h interval) in urine accounted for 79.3% (PEV) and 56.1% (NaVP) while, in faeces accounted for 9.1% (PEV) and 26.1% (NaVP) of total administered dose (14 days). The difference is attributable to a higher excretion of radioactivity in the bile for NaVP. The missing fraction in the total radioactivity balance is probably excreted in expired air, as observed in single dose studies. Radioactivity excreted in bile (0-8 h interval of the last 14th day) accounted for 5.1% (NaVP) and 0.23% (PEV) of the total administered dose (14 days). A possible explanation of this difference may be a different metabolism pattern for the two compounds. The negligible biliary excretion observed after PEV administration is probably due to an inhibition of the glucuronation of valproic acid (or other metabolites) caused by the pivalic acid. Due to the presence of the enterohepatic recycle, the radioactivity levels in intestine, 0.5 and 2 h after administration, were higher after NaVP administration. According to higher plasma levels, the radioactivity concentrations in liver, kidneys and some fat tissues were found to be slightly higher after PEV administration. At 120 h after the last treatment of both compounds, relevant tissue concentrations were observed in mesenteric lymphnodes, perirenal and brown fat. The tissue-plasma radio activity ratio appeared quite similar for the two compounds.
Administration, Oral↗
Pharmacokinetic study in rats after single intravenous and oral administrations of [14C]-ITF-296.
Pharmacokinetics of [14C]-ITF-296 and its metabolites, ITF-1124 and ITF-1577, were studied in rats after a single intravenous (2.5 mg/kg) and oral (10 mg/kg) administration. Radioactivity was measured by LSC while unchanged drug and its metabolites in plasma were assayed by an HPLC-UV method. The absorption of [14C]-ITF-296 after oral administration is practically complete. Elimination of radioactivity occurs mainly in urine (higher than 80%) and the recovery of the dose (higher than 95%) takes place up to 96 h after both treatments. Both by i.v. and p.o. route the results show that the radioactivity is largely excreted in the bile and reabsorbed in the intestine. The tissue distribution study indicates that there is no accumulation or localization of radioactivity in the major organs or blood and no radioactivity levels are found 96 h after either treatment. In addition, whole body autoradiography confirms the tissue distribution pattern, showing no differences between albino and pigmented rats.
Administration, Oral↗
Pharmacokinetic study in dogs and monkeys after single intravenous and oral administrations of [14C]-ITF-296.
Pharmacokinetics of [14C]-ITF-296 and its metabolites, ITF-1124 and ITF-1577, were studied in dogs and monkeys after a single intravenous (2.5 mg/kg) and oral (10 mg/kg) administration. Radioactivity was measured by LSC while unchanged drug and its metabolites in plasma were assayed by an HPLC-UV method. The absorption of [14C]-ITF-296 after oral administration is practically complete both in dogs and in monkeys. The determination of unchanged drug and its metabolites shows quite a similar profile in dogs and monkeys for ITF-296 and ITF-1124 and a different time-course for ITF-1577. Elimination of radioactivity occurs mainly in urine (namely 70-80%) for both species and the recovery of the dose (higher than 90%) takes place up to 96 h after both treatments.
Absorption↗
Disposition of premazepam, an anti-anxiety pyrrolodiazepine, in the cynomolgus monkey.
The plasma levels, tissue distribution and the urinary elimination of total radioactivity and of unchanged premazepam were determined in cynomolgus monkeys given intravenously the 14C labelled pyrrolo diazepine. Following the i.v. injection, both total 14C and the unchanged drug disappeared from the central compartment in a biphasic manner with terminal half-lives of 11.9 and 3.7 h respectively. Elimination occurred mainly via the kidneys with 58% of the administered 14C and 16% of premazepam recovered in 48 h. Tissue distribution of radioactivity (whole-body autoradiography) showed as target tissues the emunctory organs and the melanin rich choroid of the eyes and the traiv follicles. Interestingly, five min after the i.v. dose the distribution of premazepam in the brain indicated an homogeneous diffusion in the different areas with a preferential affinity for the grey matter.
Animals↗
Comparative bioavailability of Silipide, a new flavanolignan complex, in rats.
The comparative pharmacokinetics of Silipide (IdB 1016, a silybin-phosphatidylcholine complex) and silybin were investigated by measuring unconjugated and total plasma silybin levels as well as total biliary and urinary silybin excretion in rats following administration of a single oral dose (200 mg/kg as silybin). Mean peak levels of unconjugated and total silybin after IdB 1016 were 8.17 and 74.23 micrograms/ml respectively. Mean AUC (0-6 h) values were 9.78 and 232.15 h.micrograms.ml-1 indicating that about 94% of the plasma silybin is present in a conjugated form. After administration of silybin, plasma levels of both unconjugated and total compound were under the analytical detection limit. Cumulative biliary (0-24 h) and urinary (0-72 h) excretion values after administration of IdB 1016 accounted for 3.73% and 3.26% of the administered dose, respectively. After silybin administration, the biliary and urinary excretion accounted for only 0.001% and 0.032% of the dose respectively. Our results indicate a superior bioavailability of silybin administered orally as IdB 1016. This was due mainly to an impressive increase in gastrointestinal absorption.
Animals↗
Absence of dichlorobenzidine in the urine of rats, rabbits and monkeys treated with C.I. pigment yellow 13.
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3,3'-Dichlorobenzidine↗
Pharmacokinetics of recombinant human follicle stimulating hormone after intravenous, intramuscular, and subcutaneous administration in monkeys, and comparison with intravenous administration of urinary follicle stimulating hormone.
Recombinant human follicle stimulating hormone (r-hFSH; Gonal-F) is a new human FSH produced by a genetically engineered mammalian cell line (Chinese Hamster Ovary cells). To assess and compare its pharmacokinetics with urofollitropin (u-hFSH; Metrodin), extracted from the urine of postmenopausal women, we performed a cross-over study in 12 monkeys. They received 10 IU/kg iv of u-hFSH and r-hFSH. Then all received a single 10 IU/kg dose im and sc of r-hFSH. In the third phase, six monkeys received 10 IU/kg/day im of r-hFSH for 7 days when the six others received the same regimen subcutaneously. Blood was withdrawn at predetermined time points, and FSH serum concentrations were measured by an immunoenzymetric assay. Data were analyzed individually by fitting a two-compartment pharmacokinetic model for the intravenous routes and a one-compartment first-order absorption model for the intramuscular and subcutaneous routes. After intravenous administration of u-hFSH and r-hFSH, mean FSH concentration-time curves were almost parallel. AUC0-infinity was significantly smaller after r-hFSH (846 IU.hr-1/liter +/- 125) than after u-hFSH (1377 IU.hr-1/liter +/- 236) (p < 0.005; analysis of variance), because the u-hFSH immunological dose was greater (8.77 IU/kg) than the r-hFSH immunological dose (6.94 IU/kg). Thus total clearance for r-hFSH (0.008 liter/hr/kg +/- 0.001) and for u-hFSH (0.007 liter/hr/kg +/- 0.001) was almost similar. Distribution half-lives (1.5 hr +/- 0.1 and 1.8 hr +/- 0.4) and terminal half-lives (15.3 hr +/- 3.8 and 15.5 hr +/- 5.1) for r-hFSH and u-hFSH were similar.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗