Biomedical subjects
Publications and source records attributed to R Riva.
Camazepam, 5 mg/kg iv, was injected in rats and mice to study its distribution in the blood and brain. Peak blood levels were about 0.9 microgram/ml in rats and 0.6 microgram/ml in mice. Peak brain levels were about 1.5 microgram/g in rats and 0.8 microgram/g in mice. The apparent blood half-life of camazepam was 9 min in mice and 20 min in rats.
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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.
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.
The effect of carbamazepine (CBZ) and phenobarbital (PB), alone and in association, on the function of specific brain structures was studied in chronically treated epileptic patients by means of saccadic eye movements (SEMs) analysis. The relationship between daily fluctuations of CBZ plasma levels and the occurrence of intermittent side effects was also evaluated. All treatments produced a significant impairment (p less than 0.001) of SEM function as compared with a group of controls. SEM abnormalities appeared to change in relation to daily fluctuation of CBZ plasma levels. When the SEM parameters were considered separately, PB showed a significantly (p less than 0.001) more relevant sedative effect, whereas both drugs appear to produce the same effect on cerebellar and pontine functions. Although impairment of SEM function was most likely far from reaching clinical significance, it represents important information for the clinician.
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.
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.
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.
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.
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