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Biomedical subjects

F Albani

Publications and source records attributed to F Albani.

At least 55 records · Page 3Linked to original sources
PubMed1991

Effect of age on the pharmacokinetics of oral levodopa in patients with Parkinson's disease.

The influence of age on the kinetics of a standard oral dose of levodopa administered with an inhibitor of peripheral dopa decarboxylase enzymes (benserazide) has been evaluated in 40 patients with Parkinson's disease (age 34-78 y) on chronic therapy. They were divided into 2 groups, on the basis of age below (21 patients, Group A) or above (19 patients, Group B) 65 y. The area under the plasma concentration-time curve (AUC) of levodopa was significantly greater in the older group (547 versus 428 mumol.l-1.min in Group B), coupled with a reduced apparent oral clearance (8.1 versus 10.7 ml.min-1.kg-1) and a longer plasma elimination half-life (67.6 versus 54.6 min). The age of the patients was positively correlated with the AUC of levodopa (r = 0.474) and its plasma elimination half-life (r = 0.391), and was negatively correlated with clearance (r = -0.489). The findings confirm previous data on volunteers that showed a reduction in the systemic clearance of levodopa due to age, which would probably account for the finding of a greater AUC of levodopa in older patients. The observed, age-mediated differences in levodopa pharmacokinetics, albeit statistically significant, were moderate and were likely to be of only minor importance for the dosing schedule.

Administration, Oral↗
PubMed1991

Effects of acute valproic acid administration on carnitine plasma concentrations in epileptic patients.

Serial plasma samples collected after an acute administration of valproic acid, (VPA, 15 mg/kg as oral solution) in epileptic patients were selected for this study. The plasma samples were selected from three different groups of patients; patients on phenobarbital and phenytoin with clinical VPA intolerance (group A); patients on phenobarbital and phenytoin without clinical VPA toxicity (group B); and patients without phenobarbital and phenytoin and without clinical VPA toxicity (group C). Plasma samples from 6 patients per group were analyzed for carnitines and ammonia. Ammonia levels during acute study increased significantly (P less than 0.05) in patients who experienced VPA intolerance, while no changes were found in the other patients. After acute VPA administration, total carnitine was unchanged but free carnitine was decreased (P less than 0.05) and carnitine esters were increased (P less than 0.05) in all groups of patients studied. No difference in carnitine profiles was seen between patients with or without evidence of VPA administration has an important effect on carnitine metabolism. However, unlike the acute effect on ammonia metabolism, this acute effect does not seem to be correlated with any associated antiepileptic therapy, nor does it predict clinical VPA intolerance.

Adult↗
PubMed1991

Combined levodopa-anticholinergic therapy in the treatment of Parkinson's disease. Effect on levodopa bioavailability.

The effect of chronic intake of the anticholinergic drug orphenadrine on the bioavailability of levodopa was studied in six patients with Parkinson's disease. Plasma levodopa profiles and corresponding motor response to a standard dose of levodopa plus an inhibitor of peripheral L-aromatic aminoacid decarboxylase (benserazide) were followed, over a 5-h period, on two different sessions, with and without anticholinergic cotherapy. Six control patients were also included in the study for assessment of intrasubject variability in levodopa absorption under identical conditions. A considerable delay in levodopa absorption was found in one patient, and decreased absorption in an additional two patients while on anticholinergic. Patients' clinical performance corresponded well to plasma levodopa profiles. A significant impairment of basal clinical state was observed in two cases on anticholinergic withdrawal, probably as a result of pharmacodynamic interactions. Our observations suggest that chronic anticholinergic intake may contribute to a less predictable pattern of levodopa absorption and related therapeutic response in some subjects.

Adult↗
PubMed1990

Flunarizine plasma concentrations and side effects in migraine patients.

Flunarizine plasma concentrations and side effects were evaluated in migraine patients during a 3 month course of prophylactic treatment. Plasma concentrations did not correlate with daily dose (in mg/kg). Mean flunarizine levels were higher in patients showing sleepiness or sedation. Weight gain was independent of plasma concentrations. Future clinical trials of flunarizine should be supported by drug monitoring in order to clarify the relationship between plasma levels and drug effects.

Adolescent↗
PubMed1988

[Appearance of EEG abnormalities in two patients during long-term treatment with B vitamins].

Two female patients, one treated for epilepsy by phenobarbital (PB) and carbamazepine (CBZ), the other suffering from neurosis and free of any drug therapy, were given group B vitamins (riboflavin and nicotinic acid respectively) and showed during the long-term administration of these vitamins 2-3 Hz generalized electro-encephalographic (EEG) abnormalities. These EEG changes were detected incidentally and were not associated with any clinical manifestation; they disappeared progressively within several weeks after discontinuation of vitamin therapy. In our opinion, it is likely that the treatment with B vitamins was entirely responsible for the EEG changes, as one of the patients did not receive any other drug, while the other did not show any significant change of PB and CBZ plasma levels during vitamin therapy. However, other cases reported will be necessary to confirm our impressions.

Aged↗
PubMed1988

Neuroendocrinological evidence of an anti-dopaminergic effect of flunarizine.

The effect of a one month treatment with flunarizine (5 mg/day) on pituitary responsiveness to gonadotrophin-releasing hormone (GnRH), thyrotrophin-releasing hormone (TRH) and arginine infusion was assessed in 17 adolescents (11 M, 6 F) treated with the drug to prevent migraine attacks. Basal prolactin concentrations as well as the prolactin response to TRH were significantly (p less than 0.05) increased after flunarizine treatment. Flunarizine had no effect on the folliclestimulating and luteinising hormone response to GnRH stimulation, growth hormone response to arginine infusion or thyrotrophin response to TRH stimulation. Our data suggest that flunarizine may interfere with the hypothalamic-pituitary-prolactin axis decreasing dopaminergic inhibitory tonus.

Adolescent↗
PubMed1987

Simple and rapid GLC method for the determination of orphenadrine in human plasma.

A rapid and specific method has been developed for the determination of orphenadrine concentration in plasma. It involves a one-step sample preparation using n-hexane/isopropyl alcohol (98:2) extraction, and analysis by gas chromatography on a wide bore capillary column using nitrogen/phosphorus detection. This procedure considerably simplifies previously reported assays and is specific and sensitive enough for the determination of orphenadrine in plasma of patients on chronic therapy.

Chromatography, Gas↗
PubMed1987

Influence of meal ingestion time on pharmacokinetics of orally administered levodopa in parkinsonian patients.

The influence of meal ingestion time on rate and extent of oral levodopa absorption was evaluated in a group of 17 patients, after administration of their usual second daily dose of levodopa plus carbidopa (Sinemet 10:1) or benserazide (Madopar 4:1). Standard meals were consumed by the patients after they had fasted 15-17 h, on one occasion 30 min before ingestion of the levodopa "study dose" and, at another time, 2 h after ingestion of the same dose. This study dose, ranging from 50 to 250 mg levodopa, was given to the patients at 11 a.m., 4 h after their first morning dose. Time to peak plasma levodopa concentration increased threefold (from 45 +/- 23 to 134 +/- 76 min, p less than 0.001), when levodopa was administered after meals. Area under the 6-h plasma concentration-time curve for levodopa was decreased in 10 subjects, unchanged in three and higher in four after ingestion of meals, the latter finding probably resulting from an erratic absorption even at fasting. On the whole, levodopa absorption proved significantly lower (p less than 0.01), on the average 15%. Similarly, peak plasma levodopa concentrations were lower in 12 patients, unchanged in two, and higher in three, with an overall significant decrease (p less than 0.001) of 30% on the average. The data confirm the importance of meal ingestion time in relation to levodopa dose as a determinant of drug absorption.

Aged↗
PubMed1987

Systemic haemodynamics, renal and platelet function during chronic propranolol administration in patients with compensated cirrhosis.

Chronic propranolol administration is followed by some haemodynamic alterations, which may impair renal function. It has also been suggested that it may reduce platelet production of proaggregatory thromboxane (TX) A2. We therefore evaluated cardiac index (CI), systemic vascular resistance (SVR), creatinine clearance, daily sodium excretion under controlled sodium intake, platelet aggregation and platelet TXA2 production during whole blood clotting in eight patients with cirrhosis, portal hypertension and no ascites, before and after 3 months of propranolol administration. Liver function was also assessed by evaluating the galactose elimination capacity (GEC) and galactose clearance (Cgal). The expected, significant reduction of CI and increase of SVR was observed. Creatinine clearance and sodium balance were unchanged throughout the study. Furthermore, the renal prostaglandin system, as reflected by urinary prostaglandin E2 and TXB2 excretion, was also unaffected by the drug. No modification of platelet aggregation, platelet TXA2 production during whole blood clotting, GEC and Cgal was observed. We conclude that chronic propranolol administration is followed by alterations of CI and SVR, but it does not impair renal function and platelet aggregation in patients with cirrhosis, portal hypertension and no ascites. The maintenance of renal function during beta-adrenergic blockade is not due to an increased renal production of vasodilating prostaglandins.

Adult↗
PubMed1986

Altered serum protein binding of carbamazepine in disease states associated with an increased alpha 1-acid glycoprotein concentration.

The protein binding of carbamazepine (CBZ) in vitro was assessed in sera from 47 patients with various diseases known to alter alpha 1-acid glycoprotein (AAG) concentration and from 20 drug-free normal control subjects. In the patient group, AAG and albumin (HSA) concentrations ranged from 6 to 74 mumol/l and from 377 to 652 mumol/l, respectively; in the controls, protein concentrations were less variable, ranging from 11 to 26 mumol/l for AAG and from 623 to 754 mumol/l for HSA. In both the patient and the combined patient and control groups, free CBZ fractions were inversely correlated with the serum AAG concentration (r = -0.62). No significant relationship could be found between the free CBZ fraction and the serum HSA concentration. The free CBZ fraction was moderately but significantly decreased in patients with AAG levels above 26 mumol/l (the highest value found in controls) as compared either to patients with a normal AAG concentration or to control subjects (19 +/- 5% vs 23 +/- 4% and 23 +/- 2%), despite the finding of a higher HSA concentration in the control group. The data confirm AAG as an important determinant of interindividual variability in serum CBZ binding.

Adult↗
PubMed1985

Propranolol plasma levels and relief of migraine. Relationship between plasma propranolol and 4-hydroxypropranolol concentrations and clinical effects.

The relationship between propranolol and 4-hydroxypropranolol plasma concentrations and relief of migraine was assessed in 17 patients during treatment with oral racemic propranolol hydrochloride in doses of 40 to 240 mg/day. Propranolol decreased the migraine index more than 70% in 13 patients: five patients at a dosage of 40 mg/day, five patients at a dosage of 120 mg/day, and three patients at a dosage of 240 mg/day. Three patients did not achieve a good improvement of migraine at any of the doses used. The relief of migraine was not directly related to the propranolol and 4-hydroxypropranolol plasma concentrations.

Adult↗
PubMed1985

Alpha 1-acid glycoprotein concentration and serum protein binding of carbamazepine and carbamazepine-10,11 epoxide in children with epilepsy.

The relationship between the serum protein binding of carbamazepine (CBZ) and carbamazepine-10,11 epoxide (CBZ-E) and the concentration of alpha 1-acid glycoprotein (AAG) and albumin (HSA) was examined in 39 CBZ-treated epileptic children aged 4 months to 12 years. A significant inverse correlation was found between the free fraction of both compounds and serum AAG, even though changes in AAG concentration explained only part of the variation in binding. No correlation was found between the free fraction of CBZ and CBZ-E and HSA, probably due to the small intersubject variation in HSA concentration. In vitro experiments showed that both CBZ and CBZ-E were bound to HSA and to a lesser extent to AAG. At equivalent HSA concentrations, the binding of CBZ and its metabolite increased proportionately with increasing AAG concentration within the range occurring clinically.

Carbamazepine↗
PubMed1985

Determination of total and free plasma carbamazepine concentrations by enzyme multiplied immunoassay: interference with the 10,11-epoxide metabolite.

The performance of the enzyme multiplied immunoassay technique (EMIT) in the measurement of total and free plasma carbamazepine (CBZ) levels was assessed in 140 clinical specimens and compared with a reference high pressure liquid chromatography (HPLC) technique. Free drug was measured in plasma filtrates obtained by the Free Level system. Both total and free CBZ levels as determined by EMIT correlated strongly with corresponding HPLC values (r = 0.88 and 0.92, respectively). Plasma CBZ concentrations, however, were higher by EMIT than by HPLC. The degree of CBZ overestimation by EMIT was relatively small (about 14%) in whole plasma but quite considerable (35% on average) in the filtrates. As a result, estimated values of free CBZ fraction were also higher for EMIT than for HPLC. Separate experiments in vitro suggested that the discrepancies between the two methods were due to cross-reaction of the EMIT reagent with the 10,11-epoxide metabolite of CBZ. The greater degree of overestimation for the free drug can be explained by the higher proportion of less protein-bound metabolite in the filtrates. These results need to be taken into account in the interpretation of free CBZ level data from laboratories using different techniques.

Carbamazepine↗
PubMed1985

Hormonal and metabolic changes induced by flunarizine therapy: preliminary results.

The effect of 30-days of flunarizine (5 mg/day) therapy on pituitary, B-pancreatic, gonadic and adrenal function was studied in five adolescents with common migraine. Baseline concentration of growth hormone was significantly reduced after flunarizine therapy. The response of prolactin to thyrotrophin-releasing hormone was significantly increased after flunarizine therapy. The percentages of HbA1 and HbA1c were significantly higher after flunarizine therapy. The drug had no apparent effect on gonadic and adrenal function. Further studies are needed to confirm the effect of flunarizine on the hypothalamus-pituitary axis and glucose tolerance.

Adolescent↗
PubMed1985

Time-dependent interaction between phenytoin and valproic acid.

The diurnal variation in total and free plasma phenytoin (PHT) concentration at steady state was examined in eight epileptic patients receiving combination therapy with tid valproic acid (VPA) as sodium salt. Eight patients treated with PHT, but not with VPA, were studied for comparison purposes. In the absence of VPA coadministration, total and free PHT concentrations did not change significantly during the day and showed only minor intrapatient fluctuations (14 and 13%, respectively). In patients receiving VPA, the mean total PHT did not change significantly, whereas the free PHT increased during the day (p less than 0.05). The fluctuations in total and free PHT in these patients were 16 and 17% on average. In the presence of VPA, the free PHT fraction was higher than in controls (13.9 +/- 2.3% versus 8.3 +/- 1.9%; p less than 0.01) and fluctuated to a greater extent (29 versus 14% in controls; p less than 0.01), mainly as a result of combined opposite swings in both total and free concentration. The diurnal changes in free PHT concentration and fraction correlated positively with the changes in plasma VPA. An inverse relationship between total PHT concentration and plasma VPA was found in some patients. These data demonstrate that the displacement interaction between PHT and VPA is subject to diurnal variation, probably as a result of the fluctuation in plasma VPA. The implications of these findings are discussed.

Adolescent↗