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Biomedical subjects

G Segre

Publications and source records attributed to G Segre.

At least 19 recordsLinked to original sources
PubMed1992

Acetazolamide-like carbonic anhydrase inhibitors with topical ocular hypotensive activity.

New carbonic anhydrase (EC 4.2.1.1) inhibitors were synthesized as potential drugs for the topical treatment of glaucoma. They were obtained by substituting the acetyl group of acetazolamide and methazolamide with bicarboxylic acids of different chain length (C4-C6). The terminal carboxyl was either kept free or esterified with alcohols of different size (C1-C12). A gamma-aminovaleric derivative was also prepared. All compounds proved active as carbonic anhydrase inhibitors in vitro, with an average IC50 of about 0.5 microM. Some proved also to be topically active in vivo in lowering the artificially elevated intraocular pressure in rabbits. The most active compound, carrying a succinic acid side chain, is the most soluble in aqueous buffers. Its duration of action is about 8 h and it is under evaluation as a topical antiglaucoma drug. It is hypothesized that the duration of action could be longer in compounds having both the same high water solubility and partition coefficient.

Acetazolamide↗
PubMed1992

Pharmacokinetics of rufloxacin in healthy volunteers.

The plasma and urine kinetics of rufloxacin were assessed in healthy volunteers after single (100, 200, 400 and 800 mg) and multiple (300 mg followed by 150 mg daily, Group 1, and 400 mg followed by 200 mg daily, Group 2) oral doses. The kinetics of a single oral dose of 800 mg was assessed in fasting and non-fasting subjects to assess the influence of food intake on drug absorption. The AUCs were 134, 266 and 375 micrograms.h.ml-1 after 100, 200 and 400 mg, respectively. The AUC after 800 mg p.o. was 715 micrograms.h.ml-1 in fasting subjects and 614 micrograms.h.ml-1 in non-fasting subjects. The parameters of the model and the mean renal clearance values indicated some departure from linearity in rufloxacin kinetics. After multiple doses the plasma drug levels during the 6th treatment day were similar to those after the first dose in Group 1 and were about 30-40% higher after the first dose in Group 2. The half-lives after the last dose were much shorter than those estimated in the single dose studies (33-36 h and 50-80 h, respectively).

Administration, Oral↗
PubMed1992

Non-invasive prediction of aluminum bone disease in hemo- and peritoneal dialysis patients.

Between October 1987 and October of 1989, we conducted a prospective study to evaluate non-invasive test strategies for predicting aluminum bone disease (ABD) in a group of largely unselected dialysis patients based on their deferoxamine (DFO) test alone, or the combined results of their DFO test and intact 1-84 parathyroid hormone (PTH) levels. These test parameters were evaluated against the pathological diagnosis of ABD based on bone biopsy ("gold standard"). A total of 445 patients in three dialysis centers in Toronto were serially followed for their clinical, laboratory and risk parameters for renal osteodystrophy during the study, and 259 (142 PD and 117 HD) patients underwent a series of investigations which included the DFO test, measurement of intact 1-84 PTH levels, and an iliac crest bone biopsy. Serum aluminum ([Al]) level greater than or equal to 3700 nM (or 100 micrograms/liter) had a positive predictive value (PPV) of 75% for ABD in our PD and 88% in our HD patients, but its sensitivity was low (10 and 37%). Delta [Al] (that is, incremental rise of serum [Al] from baseline post-DFO) was useful in predicting ABD in our PD but not HD patients. Test combination based on delta [Al] greater than or equal to 5550 nM (or 150 microgram/liter) and PTH levels less than 20 pM (or 200 pg/ml) yielded the best PPV greater than or equal to 95% for ABD in both PD and HD patients. This test cut-off would remain highly predictive of ABD even if the prevalence of ABD decreases to as low as 5% for the PD patients and 10% for the HD patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1992

Pharmacokinetics of pramiracetam in healthy volunteers after oral administration.

The pharmacokinetics of pramiracetam was assessed using an HPLC method after oral administration of two different formulations of 600 mg (a solution and a tablet) of pramiracetam to 11 fasting volunteers. The mean kinetic parameters were: t1 = 4.7 +/- 2.4 - 4.3 +/- 2.2 h, AUC = 57.6 +/- 43.6 - 47.2 +/- 33.9 micrograms h/ml, Cmax = 6.80 +/- 3.2 - 5.80 +/- 3.3 micrograms/ml for the solution and the tablet respectively. The plasma profile of pramiracetam proved to be not highly affected by the formulation, only that the absorption rate was faster after oral administration of the drug in solution than after administration as a tablet. The half-life was very variable between subjects [2-8 hours], but less variable within subjects and it was unaffected by the formulation.

Absorption↗
PubMed1991

Influence of probenecid on P-amino hippurate kinetics.

The influence of probenecid on p-amino hippurate (PAH) kinetics was investigated in rat. Probenecid was administered i.p. (25, 50, 100, 150 and 200 mg/kg) two hours before PAH administration (25 mg/kg i.v.). The distribution and the rate of elimination of PAH was influenced by probenecid co-administration: the distribution decreased after probenecid doses higher than 150 mg/kg and the rate of elimination decreased after doses higher than 50 mg/kg.

Animals↗
PubMed1991

The sojourn time and its use in pharmacology.

A short review on some pharmacokinetic parameters (mean residence time, sojourn time, transit time) is given in relation to compartmental models and some examples and application are discussed. In particular the use of the sojourn time is suggested because this parameter can give useful informations when comparing the pharmacokinetics of different drugs or in pharmacodynamics.

Aztreonam↗
PubMed1991

Plasma kinetics of atropine and ipratropium in rats after different routes of administration evaluated by a radioreceptor assay.

Plasma kinetics of atropine and ipratropium was assessed in rat after i.v. (10 mg/kg), oral and i.p. (50 mg/kg) administration by a radioreceptor assay (RRA). The volume of the central compartment and the clearance of both drugs were very similar (about 3 L/kg and 3.5 L/h/kg respectively) while the steady state volume of distribution and the terminal half-life of atropine were higher than those of ipratropium. After i.p. administration the kinetics of ipratropium was very different from what was expected after the i.v. experiment.

Administration, Oral↗
PubMed1990

Triazolam pharmacokinetics in rats using a radioreceptor assay.

The time course of the activities arising after oral (0.33 and 1 mg/kg) and intravenous (0.33 mg/kg) administration of triazolam to rats was assessed in different tissues using a radioreceptor assay. In almost all cases the activities in plasma were lower than in liver, brain, kidney and heart showing that the drug and possibly some active metabolites distribute extensively and rapidly in all the sampled tissues. Peak plasma levels were 34 pmol/ml, 10.2 pmol/ml and 34.9 pmol/ml after 0.33 mg/kg intravenously, 0.33 mg/kg per os and 1 mg/kg p.o. respectively. The area under curve in plasma was proportional to the administered oral dose and it was much smaller after intravenous injection than after the equivalent oral dose (13.8 pmol.h/ml after the i.v. dose and 47.3 pmol.h/ml after the oral dose).

Administration, Oral↗
PubMed1990

Pharmacokinetics of bamifylline during chronic therapy.

The pharmacokinetics of bamifylline (Briofil) has been studied in 6 healthy volunteers both after acute and chronic administration. The kinetic variables were similar both after the first dose and after chronic treatment and no significant accumulation of the drug was observed after 7 days of therapy with bamifylline (600 mg b.i.d.). The analysis of minimal concentrations of bamifylline did not yield evidence of circadian variation in the kinetics of this drug; large differences among subjects and within each subject on different days may be explained by changes in drug bioavailability. Very low plasma levels of bamifylline were observed at the end of the dosing intervals in 50% of the cases; this observation does not necessarily invalidate the efficacy of this dosage regimen because the active metabolite of bamifylline (AC119) might contribute to the bronchodilator activity of this drug.

Adult↗
PubMed1989

Antagonism of aminoglutethimide and adrenocorticotropic hormone (ACTH) studied on slices of adrenal glands of the guinea-pig.

Aminoglutethimide at concentrations from 0.1 to 5 nM is able to inhibit the cortisol release elicited by adrenocorticotropic hormone (ACTH) (from 2.5 to 50 ng/ml) in guinea-pig adrenal cortex slices. The antagonism is a non-competitive one (in a Lineweaver-Burk plot), whereas other drugs (morphine, endorphin, indomethacin, etc.) inhibit ACTH competitively. This is in agreement with the known mechanism of action of aminoglutethimide, which inhibits the synthesis of cortisol by blocking reactions of enzymes such as aromatase and desmolase. From the data one can calculate the dissociation constant (Km) of ACTH with its receptor(s) to be 0.27 pg/ml and the inhibiting constant (Kl) of aminoglutethimide to be 49.78 x 10(-10) M. The maximal response of ACTH was 52.9 ng/ml.

Adrenal Glands↗
PubMed1989

Glutathione (GSH) in human stomach mucosa.

The role of glutathione and its function in patients affected by carcinoma and ulcer was studied. The dramatical decrease of this tripeptide evidenced by the authors, demonstrates its fundamental role in the above mentioned pathologies and permits to formulate a hypothesis of therapeutic presidium for some substances (e.g. cysteine), that showed to be able in recovering normal glutathione levels.

Adult↗
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

The sojourn time and its prospective use in pharmacology.

Sojourn time in a given compartment i when the material has been injected in compartment i (Sji) corresponds to the average time spent by the particles of the material in i before their definitive exit from that compartment. Sojourn time is different from the mean residence time (tji), which is the average age of the particles leaving the system. If K denotes the transfer matrix of the compartmental system, then -K-1 provides the sojourn times in each compartment given initial arrival in each of the other compartments. It can be shown that Sji = xi(s)/xj. 0/s = 0, corresponds to the value of AUC in compartment i. Since AUCi/xj,0 = Fji.AUC/xi,0 (Fji = fraction of the dose in j reaching i), one has Sji = FjiSii.AUCi corresponds to a rectangle of height equal to xj,0 and base equal to Sii. Therefore in a compartment i a drug acts on the average for a time equal to Sii and the number of molecules in it depends on the dose and on Fji. In compartments which are not sampled the value of AUC can be calculated by a simulated curve or by -K-1. From the height of the rectangle whose area is equal to AUC one should subtract the threshold theta for a given effect; the resulting rectangle should indicate the intrinsic efficacy of the drug. These considerations could be applied in pharmacology, toxicology, and chemotherapy.

Mathematics↗
PubMed1988

Fractures and vertebral bone mineral density in patients with renal osteodystrophy.

We investigated the relationship of CT determined vertebral bone mineral density (BMD), type of renal osteodystrophy, N terminal PTH levels and fracture history in 31 dialysis patients. BMD for patients with bone biopsy documented osteitis fibrosa was 1.6 standard deviation (SD) above the normal value for age and sex matched controls, while those patients with low turnover osteodystrophy had a mean BMD 1.2 SD below normal (p less than 0.0001). Three patients with osteitis fibrosa who had previously been treated with prednisone had a low BMD (1.8 SD below normal, different than O, p = 0.0015). There was no correlation between BMD and time on dialysis (r = 0.1). An N terminal PTH level greater than 150 pg/ml was a sensitive (94%) and specific (100%) method of separating those patients with osteitis fibrosa from those with low turnover osteodystrophy, while BMD was much less useful in this differentiation. A low BMD was not predictive of fracture history but the type of renal osteodystrophy was. Patients with low turnover osteodystrophy had a fracture rate of 0.2 fractures/dialysis year in comparison to those with osteitis fibrosis who had 0.1 fractures/dialysis year. Patients with the former bone disease fractured mainly axial rather than appendicular bones in contrast to those patients with osteitis fibrosa. In conclusion we found that patients with osteitis fibrosa had increased BMD compared to normal while those with low turnover osteodystrophy had decreased BMD, but that the N terminal PTH level was a better predictor of the type of bone disease present than was BMD.

Adult↗
PubMed1988

Plasma and urine pharmacokinetics of free and of short-chain carnitine after administration of carnitine in man.

To 6 healthy volunteers 30 mg/kg of L-carnitine (1,3-hydroxy-4-N-trimethylamino-butyrate) were injected intravenously and plasma levels (mumol/l) of free and short-chain carnitine were determined at different times between 0.033 and 24 h. The urinary excretion of L-carnitine and short-chain carnitine in 24 h was also measured. After a period of wash-out the subjects received 100 mg/kg of L-carnitine orally and plasma levels were determined between 0.5 and 24 h. The urinary excretion of L-carnitine was measured for a period of 18.5-33 h after treatment. 3 of the volunteers also received 30 mg/kg of L-carnitine orally. Carnitine plasma levels were determined at different times between 0.5 and 18 h, while the urinary excretion of L-carnitine was measured for 48 h following the treatment. The results could indicate the presence of saturation phenomena in the absorption process for the oral doses used; specific research is required to ascertain this phenomena. The transfer of carnitine from central to extravascular volume is relatively rapid, as is its urinary excretion. The short half-life of carnitine and acetyl-carnitine can suggest the use of new forms of administration (slow-release).

Administration, Oral↗
PubMed1988

Serum and urine kinetics of rosaprostol in volunteers.

The kinetics of rosaprostol (9-hydroxy-19,20-bis-norprostanoic acid, Rosal) and of its metabolite (3-(2-n-hexyl-5-hydroxy-cyclopentyl)propionic acid) has been determined in plasma and in urine of 10 healthy volunteers after oral administration of 500 mg of rosaprostol. The peak of rosaprostol (of 524 ng/ml) appears at 4 h, whereas that of the metabolite (of 503 ng/ml) appears earlier (2 h); therefore the relationship between the two substances does not follow the precursor-successor relationship in plasma and a compartmental model has been used to fit the data. In this model the biotransformation process occurs before entering the central compartment (first-pass effect). The mean half-life of rosaprostol is equal to about 5 h and that of the metabolite is equal to 3 h. All of rosaprostol is biotransformed and only the metabolite is partially eliminated by the urine. The urinary excretion of the metabolite represents only a small fraction of the administered dose. The urinary clearance of the metabolite is equal to 5.3 l/h. The volume of distribution of both substances is equal to 21.2 l.

Anti-Ulcer Agents↗