Carbamazepine plasma levels in children and adults: influence of age, dose, and associated therapy.
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Biomedical subjects
Publications and source records attributed to L Bossi.
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The DA11 mutant of Salmonella typhimurium, originally isolated as derepressed for the histidine operon, carries a temperature-dependent alteration in a nucleolytic enzyme specifically involved in the maturation of tRNA. As a consequence of this alteration, no detectable synthesis of any mature tRNA species occurs in DA11 upon shift at 43 degrees C, whereas many tRNA precursors, whose sizes range between 80 and 750 nucleotides, do accumulate. Kinetic studies on the synthesis and processing of these maturation intermediates show that these molecules represent different stages in the maturation pathway, most of them being the products of previous nucleolytic events. These RNA molecules are in vivo substrates of methylation and thiolation enzymes and can be cleaved in vitro to 4S RNA by wild-type but not by DA11 cell-free extract. Evidence is presented that DA11 is very probably a ribonuclease P mutant.
HisU mutants of Salmonella typhimurium are depressed in the histidine operon since they have lower intracellular concentration of histidyl-tRNAHis. In this paper we present evidences showing that a strain carrying a hisU mutation (hisUl206) is altered in a nucleolytic enzyme involved in tRNA maturation process. The analysis of several hisU mutants indicates that hisU region of bacterial genome may account for more than one function involved in tRNA biosynthesis.
1 Carbamazepine (CBZ) brain and plasma concentrations were measured in twenty-one patients undergoing brain surgery for tumour removal. The drug was administered prophylactically at doses ranging from 6.9 to 14.8 mg/kg for 4-5 days before the intervention. 2 In seventeen cases where sample were collected 10-14 h after dosing, CBZ brain levels ranged from 2.2-14.5 microgram/g. A significant linear relationship (p less than 0.01) was observed between brain and plasma concentrations with a brain/plasma ratio of 1.1 +/- 0.1. 3 Carbamazepine 10,11-epoxide (CBZ-Epox), present in all samples, could be quantified in three brain specimens. Its brain concentrations ranged from 1.5-2.7 microgram/g with a brain/plasma ratio of 1.1-1.2. 4 Parieto-occipital areas tended to show higher CBZ concentrations while lower values were found in temporal regions. Very low CBZ levels were found in two gliomas while in meningiomas CBZ levels were similar to those observed in normal tissue. 5 The data, showing a linear relationship between brain and plasma concentrations of both CBZ and its epoxide, give additional significance to the plasma level monitoring of antiepileptic drugs.
Plasma levels of DPA and CNP and associated antiepileptic drugs were measured in groups of respectively 106 and 30 epileptic patients aged from 3 to 49 years. A poor correlation between daily oral dose and plasma levels of both drug was observed when the whole group of patients was considered. A better correlation was seen in a group of adult patients who received DPA and PB. Children below 10 years of age disposed both drugs faster than adults and the difference was significant (p less than 0.01) in groups receiving PB as associated drug. Patients medicated with PB and DPA or CNP showed lower plasma levels of both drugs; on the other hand DPA appeared to cause a decrease of PB clearance which was more marked in children. The clinical significance of the fluctuations of daily plasma levels of both drugs are discussed in relationship to the schedule of administration and plasma sampling. Observations on the therapeutic ranges and adverse effect of the drugs are reported.
Adult, male, female and pregnant rats were treated with single and repeated doses of carbamazepine (CBZ). The time course of the drug concentrations in plasma and tissues was followed. In all cases, data on plasma levels were subjected to pharmacokinetic analyses. Attempts were made to relate pharmacokinetic properties of carbamazepine to its effect on pentobarbital sleeping time and on protection against electroshock, after acute and repeated administration: --it was found that male rats eliminate carbamazepine faster than females: the total body clearance (TBC) was 16 ml/min/kg and 9.4 ml/min/kg, respectively. Two dose levels (25 and 50 mg/kg) had the same pharmacokinetic properties in young rats. Pregnant rats clear CBZ to a lesser extent than controls. --CBZ was found to accelerate its own elimination after repeated administration in both adult and young rats as revealed by the shortening of its half-life and an increase of 50% in clearance. Moreover, the protection against electroshock was significantly reduced after repeated administration, compared with a single-dose administration. Repeated administration of CBZ in rats shortens pentobarbital sleeping time and decreases the pentobarbital brain level significantly.
The action of different forms of haemoglobin (oxy-, carboxy-and methaemoglobin) and myoglobin on the leakage of Rb+ out of liposomes has been investigated. The results presented will demonstrate that only methaemoglobin is particularly effective in interacting with phospholipid vesicles by changing their permeability and catalyzing a peroxidation of their unsaturated hydrocarbon chains.
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