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Biomedical subjects

G Zanolo

Publications and source records attributed to G Zanolo.

At least 19 recordsLinked to original sources
PubMed1997

Simultaneous determination of atenolol and chlorthalidone in plasma by high-performance liquid chromatography. Application to pharmacokinetic studies in man.

An HPLC method developed to detect in a single run both atenolol and chlorthalidone, extracted from plasma, using two detectors (UV for chlorthalidone and fluorometric for atenolol) connected in series, is described. The drugs were separated on an ODS column at room temperature using a 0.05 M sodium dodecyl sulphate in phosphate buffer (pH 5.8)-n-propanol (95:5, v/v) solution, delivered at a flow-rate of 1.3 ml/min. Having ascertained the sensitivity (10 ng/ml of both drugs) and the intra-day reproducibility (pre-study validation), the reliability of the method was verified by inter-day assays (within-study validation) carried out during the analysis of plasma samples collected from healthy volunteers after single-dose treatment with atenolol+chlorthalidone tablets (pharmaceutical preparations containing 100+25 mg and 50+12.5 mg of the two drugs, respectively).

Antihypertensive Agents↗
PubMed1996

Determination of selenium in plasma, urine and tissues, of standard diet-fed rats and dogs by ETA-atomic absorption spectroscopy with Zeeman background correction.

The method described was developed to be applied in determination of selenium in biological matrices (plasma, urine and tissues) using ETA-AAS with Zeeman background correction. These matrices were obtained from non-fasting S.D. rats and Beagle dogs of both sexes in order to acquire data on the endogenous levels of selenium in these laboratory animals when fed with standard diets. For tissue digestion, a simple procedure using the strong organic base, Soluene 350, was adopted. Precision assays were carried out monitoring Se(IV) levels in spiked matrices (range from 25 to 200 ng) and obtaining relative standard deviations (RSD%) in the range from 3.2% to 14.5% (intra-day) and from 7.6% to 15.9% (inter-day). Accuracy assays gave relative errors (RE%) in the range from -6.5 to 4.2% (intra-day) and from -5.5% to 5.7% (inter-day). The validity of the method was checked on reference material (NBS SRM 1577 bovine liver) and the values obtained correlated with the certified ones. The detection limit assumed was 0.9 ng/ml, whereas the quantitation limit of selenium in matrices ranged from 2 to 5 ng/ml (or g), depending on the kind of sample.

Animals↗
PubMed1995

Pharmacokinetics of recombinant human luteinizing hormone after intravenous, intramuscular, and subcutaneous administration in monkeys and comparison with intravenous administration of pituitary human luteinizing hormone.

To assess the pharmacokinetics of recombinant human LH (rhLH) in monkeys, we measured serum LH levels after single iv injection and after single and repeated doses by the im or sc route. A single iv bolus of 400 IU/kg rhLH or pituitary hLH (phLH) in six cynomolgus monkeys resulted in parallel concentration-time curves. The initial and terminal half-lives of rhLH (0.8 and 11 h) were comparable to those of phLH (0.6 and 10 h). The serum levels of phLH were consistently higher due to the fact that the immunological dose of phLH was higher. Administration of increasing iv doses of rhLH (10, 63, and 400 IU/kg) to six monkeys showed that the pharmacokinetics are linear over this dose range. The total clearance for the two higher doses was 0.03 L/h.kg. Systemic bioavailability was 50% after a single sc injection of 400 IU/kg and 61% after a single im injection of the same dose. The peak concentration (180 IU/L) after im injection was reached after 2.7 h. This was higher and sooner than after sc injection (110 IU/L after 5.3 h). The terminal half-life by both routes was similar to that seen after iv injection (11 h). Daily sc or im administration of 63 IU/kg for 7 days confirmed these findings. There was no accumulation of rhLH. Some monkeys developed antibodies, especially after repeated administration. They were excluded from the analysis. No significant local or systemic adverse events occurred.

Animals↗
PubMed1993

Pharmacokinetics of glucosamine in man.

The pharmacokinetics of glucosamine sulfate (CAS 29031-19-4) was investigated in 6 healthy male volunteers (2 per administration route) using 14C uniformly labelled glucosamine sulfate and administering it in single dose by intravenous (i.v.), intramuscular (i.m.) or oral route. The results show that after i.v. administration the radioactivity due to glucosamine appears in plasma and is rapidly eliminated, with an initial t1/2 of 0.28 h. 1-2 h after administration the radioactivity due to glucosamine disappears almost completely and is replaced by a radioactivity originating from plasma proteins, in which glucosamine or its metabolites are incorporated. This radioactivity reaches a peak after 8-10 h and then declines with a t1/2 of 70 h. About 28% of the administered radioactivity is recovered in the urine of the 120 h following the administration and less than 1% is recovered in the feces. After i.m. administration similar pharmacokinetic patterns are observed. After oral administration a proportion close to 90% of glucosamine sulfate is absorbed. Free glucosamine is not detectable in plasma. The radioactivity incorporated in the plasma proteins follows pharmacokinetic patterns which are similar to those after i.v. or i.m. administration, but its concentration in plasma is about 5 times smaller than that after parenteral administration. The AUC after oral administration is 26% of that after i.v., or i.m. administration. The smaller plasma levels of radioactivity after oral administration are probably due to a first pass effect in the liver which metabolizes a notable proportion of glucosamine into smaller molecules and ultimately to CO2, water and urea.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1991

Gas chromatographic-mass spectrometric determination of ethyl carbamate as the xanthylamide derivative in Italian aqua vitae (grappa) samples.

A selective reaction of ethyl carbamate (urethane) and methyl urethane (urethylane), as internal standard, with xanthydrol was effected to detect urethane after extraction from Italian aqua vitae (grappa) samples. The xanthylamides formed were determined by gas chromatography-mass spectrometry in the selected ion monitoring mode on an apolar DB 5 silica column. The linearity of the method was tested from 10 to 1000 micrograms/l, with a detection limit of 1 micrograms/l.

Gas Chromatography-Mass Spectrometry↗
PubMed1991

Linearity of levodropropizine, a new antitussive drug, in the healthy volunteer.

The object of this study was to determine whether the pharmacokinetics of levodropropizine were linear. Twelve healthy adult male volunteers received oral doses use of 30, 60 and 90 mg of levodropropizine. A cross-over design was used. With the exception of Cmax, and AUC the pharmacokinetics of levodropropizine in the dose range studied are similar. The relationship between the doses and AUCs and the statistical comparison of AUCs (Anova test and Westlake test) confirm that in the range 30-90 mg the plasma pharmacokinetics of levodropropizine are linear.

Adult↗
PubMed1991

Distribution and excretion of teicoplanin in rats after single and repeated intravenous administration.

After the i.v. administration of a single 10 mg/Kg dose of [14C] teicoplanin to rats, no substantial differences were found between males and females as regards the hematic profile, the excretion pattern and tissue distribution. About 74% of the administered radioactivity was recovered in the 0-120 hours interval and more than 90% of this amount was found in the first 24 hours. In the 0-120 hour interval, 7% of the dose was excreted with the faeces, while the total 14C excreted (including the cage washing) was 82% of the dose. A high affinity of [14C] teicoplanin for the kidneys and especially for the cortex area was displayed in the distribution study. Similar findings were observed when 7 intravenous doses (10 mg/Kg each) were given to male rats at 24 hour intervals. The percentage of the total dose found in urine seven days after the last administration remained close to 70% and also the excretion data observed in each collection interval after the last treatment were comparable with those obtained in the single dose study. The distribution in tissues was very similar to that of the single dose experiment. The high 14C concentration level found in the kidneys of animals killed at 5 min after the last treatment was cleared with a disappearance rate comparable with that observed in the single dose experiment.

Animals↗
PubMed1989

Capillary gas chromatographic determination of epomediol in human plasma and urine using a rapid solid-phase extraction.

A simple and precise method for the quantitation of epomediol in human plasma and urine is described. Each biological sample is added with the internal standard and applied directly to an Extrelut-1 solid-phase column. After absorption the column is eluted with chloroform and the eluate is evaporated to dryness. The residue, reconstituted in ethanol, is analysed by capillary gas chromatography. No interferences from possible metabolites or endogenous constituents can be noted. The method has been applied to human pharmacokinetic studies: the results of a subacute administration to volunteers are presented.

Bridged Bicyclo Compounds, Heterocyclic↗
PubMed1989

Determination of cyclic butylboronate esters of some 1,2- and 2,3-diols in plasma by high-resolution gas chromatography/mass spectrometry.

A gas chromatographic/mass spectrometric analytical procedure is described to determine glycols in plasma as cyclic butyl boronate esters. The method, involving a pre-deproteinization step, required only 0.25 ml of plasma and a short time (20 min) to react with the derivatizing agent (butyl boronic acid). The gas chromatographic separation on a CP Sil 8 CB silica capillary column coupled to a mass detector assured a complete identification of the compounds. The analytical recoveries (greater than 95%) with low coefficient of variation (4-11%) assured the feasibility of the method over a concentration range from 5 to 1000 micrograms ml-1 for each glycol. The lower detection limits, namely 1-5 micrograms ml-1, confirmed the sensitivity of the method.

Animals↗
PubMed1989

Metabolism and excretion of 14C-tiropramide after single intravenous or peroral administration to the rat.

The study was performed with 14C-tiropramide hydrochloride, i.e. O-(2-diethylamino-ethyl)-N-benzoyl-[DL-(U-14C)tyrosyl]-dipropylamide+ ++ hydrochloride, with a specific activity of 466.16 microCi/mmol. For the study of pulmonary, urinary and fecal excretion the substance was administered in single intravenous (i.v.) doses of 4 mg/kg to 4 rats (2 males and 2 females) and in single peroral (p.o.) doses of 10 mg/kg to other 4 rats (2 males and 2 females). For the study of biliary excretion 4 mg/kg of 14C-tiropramide hydrochloride were administered in single i.v. doses to 4 rats (2 males and 2 females) anesthetized with urethane and the bile was collected from the choledocus in the 8 h following administration. The radioactivity in the expired CO2, urine feces and bile was measured by scintillometry. The radioactive substances were extracted, separated by TLC and identified by comparison of their Rf values with those of putative metabolites with known chemical structure. The following results were obtained. Radioactivity in the expired CO2: No radioactivity was found, either after i.v. or p.o. administration. Radioactivity in urine: In the 48 h after administration 37% of the i.v. administered radioactivity and 31% of the p.o. administered radioactivity was recovered in the urine. Six basic substances could be identified. In order of decreasing abundance these were CR 1166, CR 1098, tiropramide, CR 1034, CR 1919 and CR 1938. Radioactivity in feces: In the 120 h after administration 60% of the i.v. administered radioactivity and 56% of the p.o. administered radioactivity was recovered in the feces.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1989

Distribution of tiropramide and metabolites after single intravenous or peroral administration of 14C-tiropramide to the rat.

The study was performed with 14C-tiropramide hydrochloride, i.e. O-(2-diethylamino-ethyl)-N-benzoyl-[DL-(U-14C)tyrosyl]-dipropylamide+ ++ hydrochloride, with a specific activity of 466.16 microCi/mmol. The substance was administered in single intravenous (i.v.) doses of 4 mg/kg to 16 rats (8 males and 8 females) and in single peroral (p.o.) doses of 10 mg/kg to other 16 rats (8 males and 8 females). The radioactivity in plasma, in several organs and tissues and in gastrointestinal contents was measured by scintillometry. After i.v. administration the radioactivity is rapidly found in all investigated organs and tissues and also in the stomach contents. The radioactivity is concentrated in the liver and kidney, and also in other organs, as the pancreas and the salivary glands. After 120 h the radioactivity is small in the organs but still appreciably present in the colon content. The radioactivity crosses the blood-brain barrier. Deep compartments were not found. After p.o. administration the radioactivity is rapidly found in the organs and is particularly concentrated in the liver, showing a rapid absorption from the gastrointestinal tract. Besides the obvious higher concentration of radioactivity in the stomach and small intestine in the initial times after p.o. administration, the distribution and elimination pattern from the organs do not substantially differ from those found after i.v. administration. The distribution pattern found using the scintillographic method were confirmed by an autoradiographic study made on 12 non-pregnant rats (10 males and 2 females) and on 7 rats at the 13th day of pregnancy and 7 rats at the 18th day of pregnancy.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1988

Pharmacokinetics of flunoxaprofen in rats, dogs, and monkeys.

The kinetics of flunoxaprofen, an anti-inflammatory nonsteroidal drug, was studied in rats (Charles River), dogs (beagles), and monkeys (Macaca fascicularis). Plasma levels, after oral and iv administration of 20-40 mg/kg, and urinary excretion were followed for 24-72 h; the determinations were performed by gas chromatography. Levels in various organs and in rat bile were also determined. The pharmacokinetic parameters show noteworthy similarities in the three species studied: high bioavailability, extensive biotransformations with small urinary excretion of unmodified drug, total clearance between 40 and 50 mL/h/kg, and peak plasma levels of approximately 200 micrograms/mL. Rats show a high value in volume of distribution (2 L/kg), whereas dogs and monkeys show a volume of distribution between 0.13 and 0.18 L/kg. In the rat, the half-life of the drug is approximately 70 h, whereas in the dog and monkey, a half-life of approximately 2 h was found.

Administration, Oral↗
PubMed1988

Tiropramide and metabolites in blood and plasma after intravenous or peroral administration of 14C-tiropramide to the rat.

The study was performed with 14C-tiropramide hydrochloride (O-(2-diethylamino-ethyl)-N-benzoyl-[DL-U-14C-tyrosyl]-dipropyl-amide hydrochloride) with a specific activity of 466.16 muCi/mmol. The substance was administered in single i.v. doses of 4 mg/kg to 18 male and 18 female rats or p.o. doses of 10 mg/kg to 16 male and 16 female rats. The radioactivity in blood and plasma was measured by scintillometry. The radioactive substances were extracted, separated by TLC and identified by comparison of their Rf values with those of putative metabolites with known chemical structure. After i.v. administration the parent substance tiropramide and 5 metabolites were identified in plasma. Tiropramide was the most abundant substance with an AUC equal to 51% of the AUC of total radioactivity. After p.o. administration the parent tiropramide and 5 metabolites were identified. Tiropramide was the most abundant substance till the 1st h. Then the metabolite CR 1098 ((+-)a-benzoylamino-4-(2-ethylamino-ethoxy)-N, N-dipropyl-benzenepropanamide) prevailed. The Cmax of tiropramide was reached at 0.5 h with 1183 nmol/l. The AUC of tiropramide was 19% of the AUC of total radioactivity. It appears that after p.o. administration the biotransformation of tiropramide is more intense than after i.v. administration. The absolute bioavailability of total radioactivity calculated on the ratio between the p.o. and i.v. AUC was 0.67, that of tiropramide was 0.23. The difference between the absolute bioavailability of total radioactivity and that of tiropramide is probably due to a first-pass effect and a more intense biotransformation of the substance after p.o. administration.

Administration, Oral↗
PubMed1986

Pharmacokinetics of glucosamine in the dog and in man.

The pharmacokinetics, organ distribution, metabolism and excretion of glucosamine were studied in the dog giving uniformly labelled [14C]-glucosamine (sulfate), i.v. or orally, in single doses. Immediately after i.v. administration, the radioactivity in plasma is due to glucosamine, and freely diffuses into organs and tissues. This radioactivity disappears quickly from plasma (initial t1/2 = 13 min, terminal t1/2 = 118 min). After 30-60 min the radioactivity in plasma is no longer due to glucosamine, but is incorporated into alpha- and beta-globulins. The protein-incorporated radioactivity is found already 20-30 min after i.v. administration, reaches a peak after 8 h and then slowly disappears, with a t1/2 = 2.9 days. Of the administered radioactivity, more than 34% is excreted in the urine, mainly as glucosamine, and 1.7% is excreted in the feces. Radioactivity is excreted also as [14C]-CO2 in the expired air. The radioactivity, after i.v. administration, diffuses rapidly from blood into the body. Some organs show an active uptake of radioactivity, e.g. the liver and the kidney. Other tissues, such as the articular cartilage, also have an active uptake. In most other organs the radioactivity found can be explained by passive diffusion processes from plasma. After oral administration of a single dose of [14C]-glucosamine the radioactivity is quickly and almost completely absorbed from the gastrointestinal tract. The pattern of disappearance, metabolic transformation, tissue distribution and excretion of the radioactivity are consistent with those found after i.v. administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1984

Absorption, distribution and excretion of radioactivity after a single intravenous or oral administration of [14C] glucosamine to the rat.

Blood levels, tissue distribution and excretion patterns of radioactivity were studied in the rat after administration of [14C] glucosamine sulphate by the intravenous or oral route. After intravenous administration, plasma radioactivity declined in the first 30 min, then increased, reaching a peak at the 2nd hour, and disappeared, with a half-disappearance time of 28 hours. The radioactivity diffused rapidly in the tissues. Higher levels than in plasma were reached in the liver and kidneys. There was early incorporation of radioactivity in the skeletal tissues (cartilage and bone). About 50% of the administered radioactivity was excreted with the expired CO2 and about 35% with the urine. Faecal excretion was small (2% of the administered dose). After oral administration, radioactivity was quickly found in plasma, where it reached a peak at 4 hours. It then declined slowly, with biphasic kinetics. The tissue distribution, including uptake in the skeleton, repeated the pattern found after intravenous administration. There was only small faecal excretion, showing an almost complete bioavailability of glucosamine given orally, and the large excretion with the CO2 (82%) showed that glucosamine is to a large extent broken down to smaller fragments. Autoradiographic studies confirmed the tissue distribution pattern and showed in more detail the tissue localization of radioactivity.

Administration, Oral↗
PubMed1984

Rifaximin (L/105), a new topical intestinal antibiotic: pharmacokinetic study after single oral administration of 3H-rifaximin to rats.

Tritiated rifaximin was administered in a single oral dose of 10 mg/kg (specific activity 8.998 microCi/mg) and 100 mg/kg (specific activity 0.786 microCi/mg) to rats. After treatment, at fixed times, the animals were sacrificed and the radioactivity in plasma, urine, feces, and in the principal organs and tissues was measured. The radioactivity present in the feces of the two groups of rats was more than 95% of the administered dose, while the amounts found in the urine ranged between 1.15% and 1.5% of the dose. In the plasma and tissues the radioactivity levels were very low. This evidence confirmed the scanty gastroenteric absorption of L/105. Furthermore, as the radioactivity levels maintained almost the same value during the trial, there was the possibility that the amounts found were in part due to isotopic exchange between tritium of 3H-L/105 and hydrogen of water.

Administration, Oral↗