Biomedical subjects

R Urso

Publications and source records attributed to R Urso.

At least 19 recordsLinked to original sources

PubMed1994

[The pharmacokinetics of antibiotics: parenteral and oral administration, distribution in the organism, elimination].

The efficacy of antimicrobial therapy is largely dependent on the pharmacokinetics of the drug. Pharmacokinetics is the study of the kinetics, that is of the movements of drugs in the body fluids and tissue cells. Often, despite the complexity of mammalian organism, relatively simple compartmental systems are capable to describe the kinetics of many drugs and to provide a rationale in interpreting the experimental results. As most bacterial infections are localized in tissues, the pharmacokinetic modelling of antimicrobial agents should mainly be devoted to clarify the relationship between plasma and tissue drug levels, the former being easily accessible to sampling and the latter more closely related to therapeutic efficacy. In this paper an introduction to pharmacokinetic modelling is presented and the pharmacokinetics of many antimicrobial drugs is discussed.

Animals↗

PubMed1993

Pharmacokinetics of exogenous adenosine in man after infusion.

The plasma kinetics of adenosine was investigated in healthy volunteers after a 1 minute infusion of 2.5, 5 and 10 mg (38.79 and 148 micrograms.kg-1 respectively) and after infusion of 200 micrograms.kg-1 in 10 min followed by 400 micrograms.kg-1 in 10 min. As the dose in the 1 min infusion study was increased the mean CL of adenosine decreased (10.7, 4.70 and 4.14 l.min-1, respectively), its mean half-life increased (0.91, 1.24 and 1.86 min, respectively), and the mean volume of distribution did not show any clear trend (8-13 l). After the 20 minute infusion the plasma level of adenosine reached a peak value comparable to that observed after infusion of 5 mg in 1 min (about 0.5 micrograms.ml-1), but the mean clearance and half-life were significantly different (12.1 l.min-1 and 0.63 min respectively). In all the subjects the plasma concentration of adenosine had returned to the baseline value in 5-15 min after the end of the infusion.

Adenosine↗

PubMed1993

Pharmacokinetics and pharmacodynamics of dermatan sulfate after intravenous and intramuscular administration to healthy volunteers.

The pharmacokinetics and pharmacodynamics of dermatan sulfate (DS) was investigated in healthy volunteers (two groups, namely group A: 6 subjects, group B: 8 subjects). The subjects of group A received 100 mg of DS both i.v. and i.m. and the subjects of group B received 400 mg of DS both i.v. and i.m. in two different days. The resulting anticoagulant activities were assessed by the activated partial thromboplastin time (aPTT) and the pharmacokinetic parameters were calculated from the plasma concentrations of DS measured by a chromogenic assay. The plasma concentrations of DS were fitted by linear and non-linear elimination models (i.e. assuming that the drug elimination follows Michaelis-Menten kinetics). Some evidence of non-linear kinetics was given by the observation that the mean terminal half-life and clearance estimated by the linear model were not independent of the i.v. dose (0.83 +/- 0.1 and 1.74 +/- 0.21 hours and 4.94 +/- 0.64 and 2.67 +/- 0.27 l/h after 100 and 400 mg i.v. respectively. Moreover the mean half-lives estimated after i.m. administrations were much higher than the values estimated after the i.v. dose (2.03 +/- 0.74 and 3.54 +/- 1.3 hours after 100 and 400 mg) and linear models failed to fit simultaneously the DS plasma concentrations after both the administration routes. Using the linear model, the mean drug bioavailability after i.m. administration was estimated to be about 30% and 80% after the 100- and the 400-mg dose respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

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

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

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↗