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Biomedical subjects

M Furlanut

Publications and source records attributed to M Furlanut.

At least 55 records · Page 3Linked to original sources

Oral and intravenous disposition of cyclosporine in psoriatic patients.

After informed consent was obtained and with the approval of the Local Ethical Committee, cyclosporine A (CsA) kinetics was studied in 63 psoriatic patients by giving them 2.5 mg/kg CsA orally. In order to calculate oral bioavailability, F, 22 patients were given the same dose i.v. Values of the calculated kinetic parameters were oral F = 22-63%; half-life, t1/2 beta, = 11.05-13.70 h; volume of distribution, Vd, = 4.00-5.02/L/kg; total body clearance, Cl, = 4.25-4.14 ml/min/kg. The area under the blood concentration time curve was more closely related to the dose (r = 0.66) than were trough levels (r = 0.52). No significant relationship was observed between the kinetic parameters studied and the age of the patient.

Administration, Oral↗

Somatomedin C (insulin-like growth factor 1) levels decrease during acute changes of stress related hormones. Relevance for fibromyalgia.

OBJECTIVE: To determine the effects of stress hormones on insulin-like growth factor 1 (IGF-1). METHODS: Insulin induced hypoglycemia (< 3 mmol/l) and clonidine induced depression of noradrenergic tone were used to assess the acute effects of cortisol, human growth hormone (hGH), and norepinephrine (NE). RESULTS: Despite the increase of hGH during hypoglycemia, a statistically significant decrease of IGF-1 was observed along with the expected rise of cortisol and NE. To eliminate the role played by NE, NE tone was depressed by administering clonidine. A statistically significant decrease of IGF-1 was also observed. CONCLUSION: Acute cortisol release or a NE decrease induce low IGF-1 levels.

Clonidine↗

Plasma levels of levodopa and its main metabolites in parkinsonian patients after conventional and controlled-release levodopa-carbidopa associations.

The paper reports plasma levels of levodopa (LD), its main metabolites [dopamine, dihydroxyphenylacetic acid, homovanillic acid, 3-O-methyldopa (3-O-MD)] and carbidopa in 14 parkinsonian patients first treated with Sinemet and thereafter with Sinemet-CR4. A good relationship was observed between LD plasma levels and pharmacological effects. While the LD area under the curve increased after Sinemet-CR4, the same was not observed with metabolites, except with 3-O-MD. The experiments in volunteer subjects confirmed the increase in 3-O-MD in plasma after Sinemet-CR4. Higher levels were observed also in the CSF with a reduction of LD concentrations. This seems to corroborate the hypothesis of an interference with LD passage through the blood-brain barrier in humans.

3,4-Dihydroxyphenylacetic Acid↗

Pharmacokinetic optimisation of tricyclic antidepressant therapy.

Pharmacokinetics has greatly contributed to the elucidation of the variability in clinical response to antidepressants in terms of differences in plasma concentrations due to genetic constitution, age, associated diseases and drug interactions. Despite no general agreement, therapeutic and toxic concentrations have been suggested for some tricyclic antidepressants (TCAs) [amitriptyline, nortriptyline, imipramine, desipramine]. Predictive techniques may be implemented on the basis of which starting TCA dosages may be selected to reach more rapidly those concentrations at which efficacy is more probable. Therapeutic drug monitoring may thereafter assist the clinician in refining the individualisation of the dosage regimen.

Adult↗

Chlorpromazine disposition in relation to age in children.

The pharmacokinetics of chlorpromazine after intravenous infusion were studied in 25 children. The pharmacokinetic parameters studied are markedly different from those reported for adults. A clear relationship was demonstrated between age, serum terminal half-life (r = 0.75) and systemic clearance (r = -0.43). It appears that the pharmacokinetics of chlorpromazine are more rapid in children than in adults.

Adolescent↗

Imipramine pharmacokinetics in depressed geriatric patients.

Pharmacokinetics of single dose (25 mg i.m.) of imipramine was studied in geriatric and young adult patients with mood disorders requiring antidepressant treatment. Imipramine and its principal metabolites were determined by means of a high performance liquid chromatography method with electrochemical detection. Serum concentrations analysis was performed according to a bicompartmental open model. A relationship between age and kinetic parameters such as area under the curve, elimination phase constant, half-life and total body clearance was observed. Significant differences were demonstrated between elderly and young adult patients when comparing these parameters. It is concluded that geriatric patients treated with imipramine should receive doses of about 60% of those of young adults.

Adult↗

Pharmacokinetics of cefonicid in children.

The pharmacokinetics of cefonicid was studied in 17 children requiring antibiotic treatment for respiratory or urinary tract infections. After informed consent had been obtained from the parents, a single dose of cefonicid 50 mg/kg/body weight was given by intramuscular injection. The mean peak serum concentration of 212.63 micrograms/ml was reached at 1.00 h, as absorption occurred at a very fast rate with a mean constant of 3.24 h-1. Mean values for half-life, apparent volume of distribution (Vz), total body clearance (CL), and renal clearance (CLR) were 3.24 h, 0.21 l.kg-1, 16.67 ml.min-1 and 13.60 ml.min-1 respectively. There was an inverse relationship between age and Vz, whereas CL and CLR were positively correlated with age. Cefonicid concentrations in urine were many times higher than the MICs of susceptible strains of bacteria. The study demonstrated that i.m. cefonicid 50 mg.kg-1 gave serum concentrations well within the therapeutic range for susceptible bacteria, and that its pharmacokinetic properties allow single daily doses to be used to treat infections in children.

Absorption↗

Double-blind placebo cross-over study of long-acting (chlordesmethyldiazepam) versus short-acting (lorazepam) benzodiazepines in generalized anxiety disorders.

Chlordesmethyldiazepam a long-acting benzodiazepine was compared with lorazepam a short-acting one in a double-blind placebo cross-over study against generalized anxiety disorders. Chlordesmethyldiazepam therapy was more effective than lorazepam. Clinical efficacy, drowsiness and insomnia seem well correlated with pharmacokinetic properties of these two benzodiazepines. These results further support the use of a long-acting benzodiazepine rather than a short-acting one as an anti-anxiety agent.

Adult↗

Pharmacokinetics of benperidol in volunteers after oral administration.

Benperidol in a 4 mg single dose was administered orally to five healthy male volunteers. The drug was rapidly absorbed (tmax = 2.27 +/- 0.57 h) and largely distributed, the volume of distribution being 5.19 +/- 1.99 l.kg-1. Elimination half-life was 7.65 +/- 2.14 h. Urinary excretion represented only a minimal fraction of ingested dose (0.1 +/- 0.007%). Variability of the area under the curve makes a first-pass metabolism a reasonable possibility. Acute dystonias appeared in two subjects.

Administration, Oral↗

Stereospecific disposition of flunoxaprofen enantiomers in human beings.

The absorption and disposition kinetics of the enantiomers of the nonsteroidal antiinflammatory drug flunoxaprofen were studied in six healthy volunteers after oral administration of either R,S(+/-)-flunoxaprofen or R(-)-flunoxaprofen. The apparent values of the volume of distribution and systemic clearance of the S(+)-enantiomer were significantly lower than those of the R(-)-enantiomer. There was no significant difference in the absorption and elimination half-lives between the two isomers. The S(+)- to R(-)-isomer plasma concentration ratio increased with time with an apparent inversion half-time of about 50 h. This observation suggests metabolic inversion of R(-)- to S(+)-enantiomer, although the possibilities of stereoselective bioavailability or interaction between the two isomers can not be excluded.

Adult↗

Electrochemical detection of benperidol in serum for drug monitoring in humans.

A high-pressure liquid chromatographic (HPLC) method for the serum assay of benperidol is described. One ml of serum is required for a single estimation. The method involves a simple and rapid extraction step (BondElut columns), HPLC separation (C8 10-mu column), and electrochemical detection (+0.65 V). Haloperidol is used as internal standard. On the basis of this procedure, recovery (93-97%) and reproducibility (intra-assay and inter-assay coefficients of variation less than 9%) are satisfactory. The detection limit is 0.2 ng/ml of serum. After therapeutic doses, trough serum levels ranged from 3.8 to 12 ng/ml in five patients.

Benperidol↗

Primidone-carbamazepine interaction: clinical consequences.

A 15-year old boy, suffering from partial complex seizures, was treated with primidone (PR) and carbamazepine (CBZ). In spite of daily doses in the usual range (PR = 12 mg/kg, CBZ = 30 mg/kg), he was not free from seizures and serum levels of CBZ were remarkably low (4.8 micrograms/ml). A good control of seizures was obtained after gradually stopping treatment with PR. This lead to a substantial increase of CBZ serum levels to a decrease of carbamazepine-10, 11-epoxide levels and a 60% reduction in total CBZ clearance.

Adolescent↗

Plasma and tissue levels of flecainide in rats.

The time-courses of flecainide plasma and tissue levels were studied in Wistar male rats after i.v. administration (4 mg/Kg). Drug assay in plasma and tissue was performed with a specific and accurate HPLC technique. The final half lives in plasma and tissues were about 4 hours, except in the brain where the half life value was 9.8 hours. The mean tissue/plasma (T/P) ratios in myocardial, kidney, liver, skeletal and muscle tissues were 9.11, 13.8, 14.37, 6.31 respectively, while in the brain the T/P ratio rose progressively over the sampling time to 10.0. These data suggest that flecainide may accumulate in the central nervous system during prolonged treatment. Flecainide levels in adipose tissue were very low. Finally, there was an early "bulge" in the concentration curve, possibly reflecting enterohepatic circulation or non-linear elimination kinetics.

Animals↗

Carbamazepine and carbamazepine-10,11-epoxide serum concentrations in epileptic children.

Carbamazepine (CBZ) and carbamazepine-10,11-epoxide (CBZ-epox) steady-state serum concentrations were measured in 82 children who had generalized tonic-clonic, or partial seizures. There was no correlation between a given dose and serum concentrations, whether other anticonvulsant drugs were used or not. Epileptic children receiving polytherapy (CBZ associated with one or more of the following drugs: phenobarbital, primidone, phenytoin, ethosuximide) had significantly different CBZ clearance values and percent CBZ-epox than did patients given CBZ alone. Even though given lower doses, girls had higher CBZ concentrations and lower CBZ clearance values than did boys. Older girls had lower serum concentrations of CBZ-epox than did younger girls. Seizure-free children had higher CBZ serum levels and lower CBZ clearance values than did those with uncontrolled seizures. The percentage of CBZ-epox in children with uncontrolled seizures was significantly higher than in children without seizures. These data indicate that serum levels of CBZ and CBZ-epox correlate more with factors such as associated drugs, age, and sex than with administered dose. Therefore, CBZ serum level monitoring represents an essential means of individualization of anticonvulsant drug therapy.

Adolescent↗