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Biomedical subjects

R Urso

Publications and source records attributed to R Urso.

At least 37 records · Page 2Linked to original sources
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

Metabolism and disposition of intravenously administered acetyl-L-carnitine in healthy volunteers.

The pharmacokinetics of acetyl-L-carnitine hydrochloride were investigated in 6 healthy volunteers of both sexes after i.v. injection of 500 mg of the drug, expressed as inner salt. Plasma concentrations and urinary excretion of acetyl-L-carnitine (A), L-carnitine (B) and total acid soluble L-carnitine fraction were evaluated over a period lasting from 24 h before to 48 h after the administration. Plasma concentrations of A increased quickly after administration and then declined reaching base values within 12 h. Conversely, plasma concentrations of B rose more slowly, reaching a peak in 30-60 min, and then declined to base values within 24 h. Most of the injected dose of acetyl-L-carnitine was recovered in the urine during the first 24 h after administration as B and A. Mean renal clearance of both A and B during the first 12 h after injection was higher than the base values, suggesting the presence of a saturable tubular reabsorption process which may counterbalance major changes occurring in plasma concentrations of L-carnitine pattern.

Acetylcarnitine↗
PubMed1989

Doxorubicin toxicity and pharmacokinetics in old and young rats.

Doxorubicin (Dx) toxicity was compared in old (24 months) and young (6 weeks) Crl:CD(SD) BR male rats, and a clear age-related increase was found. The mortality of all animals receiving a single i.v. Dx dose was followed for 270 days. Old rats died after doses of 2.5 mg/kg, while young animals died after doses two times higher, 5 mg/kg. In old rats body weight loss started 10 to 15 days after Dx, compared to 50 to 80 days for young animals. In young and old rats pharmacokinetic and metabolic studies of Dx were conducted in vivo and in the liver perfusion model. Peak levels of Dx and areas under the time/concentration curves (AUC) in serum and in several tissues of old rats were 1.5 to 2 times higher than in young rats. Concentrations of Dx metabolites in serum and tissues (doxorubicinol, Dxol, and doxorubicinone, Dxone) in young and old rats were not noteworthy. However, higher percentages of Dxone than Dxol were found in both groups in vivo and in vitro. Old livers appeared to produce more Dxone as a percentage, particularly in the bile, which was higher. Urinary elimination of Dx markedly slowed with age; only small amounts of the metabolites were eliminated in urine. In vivo and in vitro availability of Dx and its metabolites is discussed in view of their possible role in the greater toxicity observed in 24-month-old rats.

Aging↗
PubMed1989

The pharmacokinetics of aztreonam and penetration into the bronchial secretions of critically ill patients.

The pharmacokinetics of aztreonam were studied in ten critically ill intubated patients with lower respiratory tract infections. Serum and urinary concentrations of the drug and its penetration into bronchial secretions after a 2-g intravenous bolus were measured. Using a two-compartment linear model a terminal half-life of 1.87 + 0.46 h was determined. No interpatient differences were found for half-life values, AUC or volume of distribution, except in the case of one obese patient. The greatest variability was observed in the clearance values, and in particular the extrarenal clearance which ranged from 0.3 to 9.6 1/h. Maximum concentrations in bronchial secretions were reached very quickly in the 2 h after drug administration, with a range of 4.8-18.7 mg/l. No accumulation of aztreonam after repeated doses was detected.

Adolescent↗
PubMed1988

Pharmacokinetics of mifentidine after single and multiple oral administration to healthy volunteers.

1. The pharmacokinetics of mifentidine, a new long acting histamine H2-receptor antagonist, were studied using two protocols. 2. In one study, on 5 different days six normal male subjects were given 2.5, 5, 10, or 20 mg mifentidine or placebo orally 60 min before starting a 3 h continuous gastric aspiration during which time blood samples were taken for measurement of mifentidine concentration. 3. The area under the curves of mifentidine plasma levels (AUC) vs time for the four doses was linearly related to the dose for each individual subject (r = 0.972, P less than 0.001). After doses of 2.5, 5, 10 and 20 mg, mifentidine reduced hydrogen ion output by respectively 36, 37, 60 and 75% and secretory volume by 1, 17, 40, and 47%. The effects at the two highest doses were statistically significant. AUC was correlated positively with the percentage reduction in hydrogen ion output (r = 0.802, P less than 0.001) and volume (r = 0.834, P less than 0.001) over a 3 h period. 4. In the second study, the pharmacokinetics were evaluated after once-daily treatment for 14 days in seven subjects given 10 mg and in seven others subjects given 20 mg. 5. After multiple dosing, renal clearance was similar for the two doses (11.6 +/- 2.11 l h-1 for the low dose and 17.0 +/- 2.0 l h-1 for the high dose). Plasma half-life (t1/2 lambda 2) was 16.0 +/- 3.0 h after the 10 mg dose and 11.9 +/- 1.2 h after 20 mg.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1987

Pharmacokinetics of VM 26 given intrapericardially or intravenously in patients with malignant pericardial effusion.

Three patients with lung cancer (1 SCLC, 2 NSCLC) and pericardial malignant effusion received 100 mg/m2 Teniposide (VM 26) i.v. and, 1 week later, 50 mg/m2 intrapericardially. Plasma, pericardial, and urine levels of the drug were measured in all patients after the two treatments by a HPLC assay. After intrapericardial administration, a high VM 26 concentration was found in the pericardial cavity and slow systemic drug absorption was observed. Since the drug AUC after intrapericardial administration was approximately 15-21 times that after i.v. administration, it could be that this treatment is more effective against neoplastic deposits localized in the pericardium. Even though this small series does not permit conclusions to be drawn on the efficacy of VM 26 given intrapericardially, the lack of local toxicity, minimal systemic toxicity, and the response observed in two out of three patients given intrapericardial VM 26 suggest that further investigation should be carried out on this method of VM 26 administration.

Aged↗
PubMed1987

Pharmacokinetics of enteric-coated aspirin and inhibition of platelet thromboxane A2 and vascular prostacyclin generation in humans.

We evaluated whether an enteric-coated aspirin formulation showed a "presystemic" component in its antiplatelet effect and if so would spare vascular cyclooxygenase. In six healthy volunteers, 30 to 45 minutes after ingestion of 325 mg enteric-coated aspirin, platelet thromboxane A2 generation was inhibited by about 20% before any drug could be detected in the peripheral venous blood. A further decline in thromboxane A2 generation occurred with appearance of aspirin in blood between 60 and 240 minutes. No presystemic component could be detected after 325 mg aspirin tablets. Ten patients undergoing saphenectomy received 325 mg of either aspirin tablet or enteric-coated aspirin; 12 hours later platelet thromboxane A2 and peripheral vascular prostacyclin generation were significantly reduced by 98% and 58%, respectively. The effects of the two aspirin formulations were not different. Aspirin formulations with "presystemic" component in their antiplatelet effect may not necessarily result in sparing of peripheral vascular cyclooxygenase.

Adult↗
PubMed1987

Inhibitory and inducing effects of denzimol on carbamazepine metabolism in the rat.

In vivo and in vitro alterations in carbamazepine (CBZ) metabolism and the extent of enzyme induction of the hepatic cytochrome P-450 system after chronic oral denzimol to rats were evaluated. No effect on drug-metabolizing enzymes was detected for this new anticonvulsant drug at a dose of 15 mg/kg, which is just above the anticonvulsive dose. At higher doses (60 mg/kg) denzimol significantly raised the hepatic cytochrome P-450 content, enhanced CBZ clearance and tend to shorten its elimination t1/2 and that of its active metabolite. These results, combined with those of a previous study showing impairment of CBZ metabolism after single doses of denzimol, suggest that the drug may have either inductive or inhibitory effects on microsomal mixed-function oxidase activity in the rat, depending on the dose and schedule of treatment.

Animals↗
PubMed1987

Lipophilicity and disposition of 1-aryl-piperazines in the rat.

The disposition of eight 1-aryl-piperazines was investigated in rats after i.v. administration. The concentration of 1-aryl-piperazine in body fluids and tissues was determined by h.p.l.c. or electron-capture g.l.c. Correlations of kinetics and physiological parameters with the lipophilicity of each 1-aryl-piperazine, determined by h.p.l.c. retention on a reverse-phase C18 column at neutral pH, were investigated. Binding to rat plasma proteins varied within the series, increasing with lipophilicity. For the majority of the derivatives the blood-to-plasma ratio was close to unity, implying an almost equal distribution between erythrocytes and plasma. The most lipophilic 1-aryl-piperazine of the series partitioned more into erythrocytes. The eight compounds differed widely in Vss and total Cl values and as a general trend both values increased with lipophilicity. The percentage of the dose excreted unchanged in the urine decreased progressively with increasing lipophilicity. 1-Aryl-piperazines were distributed extensively in all the tissues examined, concentrating particularly in the eliminating organs and lung. They easily entered the rat brain, Cmax values generally being reached within five minutes of parenteral injection. 1-Aryl-piperazine brain uptake increased with lipophilicity.

Animals↗
PubMed1986

Comparison of metabolism and activity of an aryldimethyltriazene and an aryldiethyltriazene.

The antitumoral activity and metabolism of 1-(4-acetylphenyl)-3,3-dimethyltriazene [pAc-(CH3)2] and 1-(4-acetylphenyl)-3,3-diethyltriazene [pAc-(C2H5)2] were studied in mice. pAc-(CH3)2 showed significant antitumoral activity against M5076 ovarian reticular cell sarcoma, L1210 leukemia, EL 4 lymphoma in mice, but not against Lewis lung carcinoma. pAc-(C2H5)2 was inactive in all these murine tumors and was much more toxic than pAc-(CH3)2. pAc-(CH3)2 and pAc-(C2H5)2 were rapidly metabolized in vitro and in vivo to their respective monoalkyltriazenes and to 4-aminoacetophenone (pAc-NH2). In vitro, 79% of the dimethyltriazene was metabolized to its monomethyl analogue, but only 27% of the diethyltriazene was metabolized to the monoethyltriazene. The monoalkytriazenes were almost completely biotransformed to pAc-NH2 by a 9000 g liver fraction. The metabolic pattern in the in vitro study was comparable to that found in vivo.

Animals↗
PubMed1986

MODDIS: a microcomputer program for model discrimination.

A computer program for a microcomputer (HP 86) is presented to discriminate between different models and to design new experiments for model discrimination. By a non-linear fitting algorithm a set of experimental data is fitted with different models suggested by the user. The parameters characterizing each model are estimated by minimizing the sum of squared residuals; different criteria are used to test the choice between two or more models at different levels of probability and the smallest number of additional experiments required for discrimination is computed. If discrimination is not achieved a direct search method is used to find the local maxima of the divergence (or information for discrimination) over a user-chosen domain of independent variables (x R'''). The x value corresponding to the absolute maximum of the divergence is the best choice to run a new experiment for discrimination.

Biometry↗
PubMed1986

Pharmacokinetics of etoposide in patients with abnormal renal and hepatic function.

Etoposide (VP16) pharmacokinetics was investigated in three groups of cancer patients: a control group of 18 patients with renal and hepatic function tests in the normal range; a group of 8 patients with renal insufficiency; and a group of 15 patients with abnormal hepatic function. In the control group plasma clearance (Clp), volume of distribution (Vd), and elimination half-life (t1/2 beta) of VP16 were, respectively, 22.8 +/- 1.0 (SE) ml/min/m2, 11.4 +/- 0.8 liters/m2, and 5.6 +/- 0.4 h. In patients with renal insufficiency Clp was 12.8 +/- 1.1 ml/min/m2, Vd was 20.8 +/- 4.9 liters/m2, and t1/2 beta was 19.2 +/- 4.7 h. A statistically significant correlation (P = 0.0000001) was found between VP16 Clp and creatinine clearance. In 12 of 15 patients with abnormal liver tests Clp, Vd, and t1/2 beta were, respectively, 27.9 +/- 2.7 ml/min/m2, 12.4 +/- 1.5 liters/m2, and 5.4 +/- 0.6 h and are thus similar to those of the control group. In the other three cases with abnormal liver function VP16 plasma levels were very low. In these cases VP16 t1/2 beta values were similar (5.1, 4.4, and 5.1 h) whereas Clp values (320, 87, and 96 ml/min/m2) and Vd values (142, 33, and 42 liters/m2) were much larger than in controls. These results suggest that VP16 doses should be reduced in patients with renal function impairment but not necessarily in patients with liver impairment. The high VP16 Vd and Clp values found in a subset of patients with liver impairment require further elucidation.

Adult↗
PubMed1986

Comparative bioavailability of aspirin from buffered, enteric-coated and plain preparations.

The bioavailability and pharmacokinetics of acetylsalicylic acid were studied in 6 volunteers, under a cross-over design, using plain compressed aspirin, two buffered preparations and an enteric-coated tablet. Absorption, calculated from urinary excretion, was complete for all the formulations. The buffered forms gave higher peak concentrations and AUC for acetylsalicylic acid than the other forms. Absorption from the enteric-coated tablet was the slowest. Acetylsalicylic acid was not measurable in plasma (less than 0.1 micrograms/ml) at any time in 3 subjects after plain and in 2 after enteric-coated aspirin. Acetylsalicylic acid was no longer measurable in plasma after 4 hours, irrespective of the preparation given.

Administration, Oral↗
PubMed1985

Ionization constants and partition coefficients of 1-arylpiperazine derivatives.

The ionization constant (pKa) and liposolubilities (log P) of fourteen 1-arylpiperazines were determined by n-octanol/buffer partition. pKa varied little across the entire series. Log P values ranged from less than 1 to about 2 for the highly lipophilic derivatives of the preset series. The results are discussed in relation to the extent to which these derivatives, known to be centrally active, may enter the brain.

Buffers↗
PubMed1985

Kinetic and pharmacological studies on estazolam in mice and man.

After i.v. and oral doses of estazolam (5 mg/kg) to mice, the drug was rapidly cleared with a beta half-life (t1/2 beta) of 0.7 h. The active metabolite, 1-oxo-estazolam, was present in traces in mouse plasma and brain. Its elimination t1/2 (beta), determined after i.v. injection of 1-oxo-estazolam (5 mg/kg) to mice, was similar to that of the parent drug in both plasma and brain. After a single oral dose of estazolam (4 mg) to four human volunteers the drug was rapidly absorbed and reached maximum plasma concentrations in one to three hours. Elimination t1/2 of estazolam in humans was 19 h. The metabolite was undetectable in human plasma after either single or multiple doses of estazolam. These results, together with the finding that 1-oxo-estazolam was less effective than estazolam, in terms of ED50 and brain concentrations necessary to antagonize leptazol convulsions and disrupt rota-rod performance in mice, indicate that the metabolite does not contribute significantly to the pharmacological effects of its parent drug.

Administration, Oral↗