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Biomedical subjects

F Albani

Publications and source records attributed to F Albani.

87 records · Page 5Linked to original sources
PubMed1982

Determination of unbound valproic acid concentration in plasma by equilibrium dialysis and gas--liquid chromatography: methodological aspects and observations in epileptic patients.

An equilibrium dialysis technique for the separation of the free (unbound) concentration of valproic acid (VPA) in plasma is described together with a sensitive gas chromatographic assay for the quantitative determination of the drug in the dialysate. The overall coefficient of variation of the method was below 10%. By using a high permeability membrane, equilibration of the drug between the plasma and the buffer compartments was obtained after about 45 min at 37 degrees C. With this dialysis time, dilutional changes in the plasma compartment were negligible and there was no significant change in the plasma-free fatty acid (FFA) concentration. No passage of protein into the buffer solution was detected. When dialysis was prolonged for up to 4 h, a significant elevation in plasma FFA (with a corresponding rise in free VPA fraction) was observed. Storage of plasma samples at temperatures ranging from 4 to 37 degrees C for 8 h or longer before dialysis also resulted in an increased value of free VPA fraction and FFA concentration. The two effects were significantly correlated. The free fraction of VPA was found to increase with increasing total plasma concentration. This effect was observed both in vitro and in vivo in the plasma of 91 patients receiving chronic VPA therapy. The methodological problems of using equilibrium dialysis techniques for determining the free fraction of VPA are highlighted.

Blood Preservation↗
PubMed1980

Rapid quantitative determination of underivatized carbamazepine, phenytoin, phenobarbital and p-hydroxyphenobarbital in biological fluids by packed column gas chromatography.

A method is described for measuring, without derivatization, the concentrations of phenobarbital, p-hydroxyphenobarbital, carbamazepine and phenytoin in biological fluids of epileptic patients undergoing long-term therapy. This method uses, at an isothermal temperature, a special column packing (GP-2% SP-2510-DA on 100-120 mesh Supelcoport). The lower limit of detection for all substances analyzed is 1 microgram/ml of biological material. The recovery of the compounds is about 95%, the reproducibility of the method is good (coefficient of variation, 4.3%). The mass spectra confirm the identity of substances eluting from the column. There is no interference from other commonly used antiepileptic drugs or endogenous substances. The method has the advantages of high specificity, sensitivity and rapidity and it appears to be suitable for the routine monitoring of blood and urine concentrations in patients receiving multi-drug therapy.

Adult↗
PubMedDate not supplied

Predictive performance of pharmacokinetic methods for phenytoin dosing: a multi-center evaluation in 282 patients with epilepsy.

A retrospective study was conducted in 282 patients with epilepsy to assess the predictive performance of pharmacokinetic methods for individualizing dosage of phenytoin. Two population-based dosing methods (population clearance method and bayesian feedback method) and one individual-based method (the so-called linearized Michaelis-Menten method) were evaluated, when applicable, for single-point and/or 2-point dose predictions of phenytoin. In single-point predictions, we found a generally low percentage of dose calculations falling inside the +/- 10% range (48.9% and 51.1% for the population clearance and the bayesian methods, respectively). In 2-point predictions, the bayesian method was 'accurate' (dose within the +/- 10% range) in approximately 54.3% or 55.0% of cases (depending on the particular method of implementation adopted). An even worse percentage of 'accurate' dose predictions (38.3%) was obtained by using the linearized Michaelis-Menten method. Our data do not confirm results from previous studies indicating a generally good performance of pharmacokinetic methods for predicting phenytoin dosage.

Adolescent↗
PubMedDate not supplied

Free and total serum concentrations of carbamazepine and carbamazepine-10,11-epoxide in infancy and childhood.

Total and free serum concentrations of carbamazepine (CBZ) and carbamazepine-10,11-epoxide (CBZ-E) at steady state were determined in 10 infants (ages 4-13 months), 10 preschool children (ages 3-5 years), and 11 school children (ages 7-11 years) receiving equivalent doses of CBZ alone. Free and total CBZ levels tended to increase with increasing age, while CBZ-E levels did not show any significant age dependency. As a result, CBZ-E/CBZ ratios were higher in infants and preschool children than in the older age group. The degree of plasma protein binding of CBZ and CBZ-E did not show any important differences among the various groups. These data provide evidence that, within a pediatric population, CBZ shows age-related dispositional changes which may be clinically important.

Age Factors↗
PubMedDate not supplied

Effect of felbamate on plasma levels of carbamazepine and its metabolites.

Felbamate (FBM) is a novel antiepileptic drug (AED) currently undergoing clinical evaluation in the United States. During a controlled clinical trial conducted at the National Institutes of Health Clinical Center, FBM was added to constant carbamazepine (CBZ) monotherapy. CBZ total concentrations were reduced during active FBM treatment (mean reduction 25%, range 10-42%, p less than 0.001). The effect was evident after the first week of treatment and reached a plateau in 2-4 weeks. To clarify the interaction mechanism, free and total concentrations of CBZ and its plasma metabolites were determined by high-performance liquid chromatography (HPLC) and ultrafiltration in four patients. In these patients, FBM treatment reduced CBZ concentrations and increased CBZ-epoxide (CBZ-E) concentrations (p less than 0.01). Free fractions of all compounds were unmodified. FBM appears to be capable of inducing CBZ metabolism. CBZ-FBM interaction may be clinically relevant.

Anticonvulsants↗
PubMedDate not supplied

Clarithromycin-carbamazepine interaction: a case report.

We report a clinically relevant interaction between a new macrolide antibiotic, clarithromycin, and carbamazepine (CBZ). In a patient receiving CBZ monotherapy, 10-day antibiotic treatment increased CBZ concentration despite concomitant CBZ dose reduction and doubled the CBZ concentration/dose ratio. Concentration of the CBZ epoxide (CBZ-E) metabolite was reduced, suggesting that the interaction occurs at a metabolic level.

Adult↗
PubMedDate not supplied

Carnitine disposition before and during valproate therapy in patients with epilepsy.

Free and total carnitine and acylcarnitine in plasma and urine samples was measured in 22 epileptic patients before and after 15 and 45 days of valproate (VPA) therapy and in 16 healthy volunteers on a single occasion. Carnitine plasma concentration and renal excretion observed in epileptic patients before VPA therapy did not differ from control values. After VPA was started, free and total plasma concentration decreased significantly (p < 0.05) from 49 +/- 17 to 35 +/- 16 at 15 days and to 35 +/- 13 nmol/ml at 45 days of therapy (free carnitine) and from 60 +/- 18 to 50 +/- 18 at 15 days and to 55 +/- 14 nmol/ml at 45 days of therapy (total carnitine), whereas acylcarnitine increased significantly (p < 0.05) from 10 +/- 8 to 14 +/- 8 at 15 days and to 18 +/- 16 nmol/ml at 45 days of therapy. Free carnitine urinary excretion decreased significantly (p < 0.05) from 200 +/- 135 to 115 +/- 76 and 118 +/- 75 mumol/24 h, whereas acylcarnitine urinary excretion increased significantly (p < 0.05) from 78 +/- 56 to 154 +/- 98 and 155 +/- 89 mumol/24 h after VPA therapy was started. As a consequence, acylcarnitine renal clearance increased significantly (+30%, p < 0.05) whereas free carnitine renal clearance did not change during VPA therapy. No difference was detected between 15 and 45 days of therapy. No patients experienced symptoms of VPA toxicity. Our results suggest that VPA in patients increases both formation and renal clearance of acylcarnitine.

Acylation↗
PubMedDate not supplied

Free concentration of carbamazepine and carbamazepine-10,11-epoxide in children and adults. Influence of age and phenobarbitone co-medication.

Total and free plasma concentrations of carbamazepine (CBZ) and carbamazepine-10,11-epoxide (CBZ-E) were determined in 39 children (aged 3 to 10 years) and 79 adults (aged 15 to 65 years) receiving long term treatment with CBZ alone or in combination with phenobarbitone (PB). Compared with the corresponding age groups treated with CBZ alone, adults and children receiving PB co-medication showed lower total and free CBZ concentrations, similar CBZ-E concentrations and higher CBZ-E/CBZ ratios. Among patients on CBZ alone, children had at any given dose lower total and free CBZ and CBZ-E concentrations than adults. Lower CBZ levels in children than in adults were also found among patients receiving phenobarbitone in combination. CBZ-E/CBZ ratios did not differ significantly between children and adults. These data provide evidence that children show an elevated free CBZ clearance with a metabolic pattern different from that observed during phenobarbitone induction.

Adult↗
PubMedDate not supplied

Concentration-effect relationship of levodopa-benserazide dispersible formulation versus standard form in the treatment of complicated motor response fluctuations in Parkinson's disease.

We compared the kinetic-dynamic profile of a postprandial dose of levodopa-benserazide dispersible formulation to that of the standard form in eight patients with parkinsonism presenting delayed or irregular patterns of after-meal levodopa dose effects. Patients were studied on two occasions, one week apart, according to an intra-subject randomized cross-over design. Thirty minutes after the consumption of a standard meal, patients received their usual levodopa-benserazide postprandial dose, on one occasion in the standard formulation and on the other one in the dispersible form. Blood venous samples for analysis of plasma levodopa concentrations were drawn at 15-minute intervals for the first 2 hours, then half-hourly until 5 hours after dosing. Motor response to the levodopa test dose was assessed by the finger tapping test at the same times as blood was sampled. The only statistically significant finding was a shorter time to peak plasma levodopa concentration with the levodopa-benserazide dispersible formulation compared with the standard form, whereas comparisons of levodopa pharmacodynamics showed little advantage of either formulation. Considering that liquid formulations of levodopa are less practical, we suggest reserving dispersible levodopa-benserazide tablets for selected patients and carefully monitoring drug dose motor response.

Aged↗