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Biomedical subjects

R Lehtovaara

Publications and source records attributed to R Lehtovaara.

At least 19 recordsLinked to original sources
PubMed1994

Effect of switching carbamazepine to oxcarbazepine on the plasma levels of neuroleptics. A case report.

Carbamazepine was switched to its 10-keto analogue oxcarbazepine among six difficult-to-treat schizophrenic or organic psychotic patients using concomitantly haloperidol, chlorpromazine or clozapine. This change resulted within 2-4 weeks in the 50-200% increase in the plasma levels of these neuroleptics and the appearance of extrapyramidal symptoms. None of the patients showed any clinical deteriotation during the following 3-6 months. The results of this case report support the idea that in contrast with carbamazepine oxcarbazepine does not induce the hepatic microsomal enzyme systems regulating the inactivation of antipsychotic drugs.

Adult↗
PubMed1987

Pharmacokinetics of chlorpropamide in epileptic patients: effects of enzyme induction and urine pH on chlorpropamide elimination.

The effects of liver enzyme induction and of urine pH on the pharmacokinetics of chlorpropamide have been studied. A single oral dose of chlorpropamide 250 mg was administered to 8 patients on antiepileptic drugs (phenytoin, carbamazepine) and to 8 healthy volunteers. The half-life of chlorpropamide was significantly shorter in the patients (34.4 h) than in the healthy volunteers (50.2 h), but the difference between the groups in the half-life of antipyrine was even more pronounced (5.1 vs 11.4 h). The clearance and volume of distribution of total chlorpropamide were significantly higher in the patients (2.99 ml X h-1 X kg-1 and 126 ml X kg-1) than in the healthy volunteers (1.60 ml X h-1 X kg-1 and 106 ml X kg-1). The unbound fraction of chlorpropamide in serum was also higher in the patients (5.7%) than in the healthy subjects (4.4%). Neither the volume of distribution nor the clearance of the free fraction of chlorpropamide differed significantly between the groups. There was a significant correlation between the half-lives of chlorpropamide and antipyrine, and the half-life of chlorpropamide also had at least as good an inverse correlation with the urinary excretion of unchanged chlorpropamide. The renal clearance of chlorpropamide correlated well with urine pH and was almost 100-fold higher at pH 7 than at pH 5. Both the metabolic and renal clearances of chlorpropamide are important in its elimination. At urine pH higher than 6.5-7, the renal clearance of chlorpropamide represents more than half its total clearance regardless the degree of induction of liver enzymes.

Adult↗
PubMed1979

Antipyretic analgesics in patients on antiepileptic drug therapy.

The effect of administration for three days of acetylsalicylic acid (1500 mg/day), phenylbutazone (300 mg/day), paracetamol (1500 mg/day) and tolfenamic acid (300 mg/day) on serum concentrations of phenytoin and carbamazepine were studied in a group of patients on continuous antiepileptic therapy. When measured 10 h after the last dose of the analgesics, the only significant effect was a decrease in total serum phenytoin after three days of phenylbutazone. When six patients on continuous phenytoin therapy took phenylbutazone for two weeks there was at two days an initial decrease, followed by a signficiant increase in total serum phenytoin and a concomitant increase in free phenytoin in serum. Even phenylbutazone was well tolerated by most of the patients. However, its use had to be discontinued on one patient due to obvious signs of phenytoin intoxication, with concomitant increases in the serum free and total phenytoin concentrations.

Adult↗
PubMed1979

Effect of increased bioavailability of phenytoin tablets on serum phenytoin concentration in epileptic out-patients.

1. The bioavailability of a brand of phenytoin tablets used in Finland was improved in 1976. In the present retrospective study serum concentrations of phenytoin, measured before and after the change of bioavailability, are compared in 50 epileptic out-patients, who for various reasons used exactly the same dose of phenytoin tablets and of other drugs despite the increased bioavailability of phenytoin. 2. The mean increase of serum phenytoin steady-state concentration was about 70% after the change of bioavailability but there were considerable interindividual differences in the response. The mean increase in serum phenytoin was only 28% in patients with serum phenytoin concentrations 5 microgram/ml or less but the mean increase was 100% in patients with serum phenytoin between 5 and 10 microgram/ml. In patients with serum phenytoin concentrations more than 10 microgram/ml the mean increase in concentration was 60-80% after the improvement of bioavailability. However, in these groups of patients some clinically manifested phenytoin intoxications enforced the patients to the control and to dose reduction obviously before the steady-state concentration of phenytoin was reached. 3. On the basis of our experiences and those reported in the literature some proposals are presented to be considered when the bioavailability of phenytoin or of another drug with a narrow therapeutic range and a dose-dependent kinetics has to be changed.

Biological Availability↗
PubMed1975

Effect of antiepileptic drugs on the elimination of various tetracycline derivatives.

Elimination of the bacteriostatics tetracycline, doxycycline, methacycline, oxytetracycline, demethylchlortetracycline and chlortetracycline was studied in healthy control persons and in patients on long-term antiepileptic therapy. The half-life of doxycycline was significantly shorter in patients than in the controls. The half-lives of other tetracycline derivatives and their excretion in urine were not significantly different between the two groups. Accordingly, in order to maintain an adequate serum level of doxycycline it should be given twice daily to patients on long-term therapy with barbiturates, diphenylhydantoin or carbamazepine. The classical tetracycline derivatives studied may be administered according to conventional principles.

Adolescent↗
PubMed1974

Interaction between doxycycline and some antiepileptic drugs.

The mean half life of doxycycline given to seven patients on long-term diphenylhydantoin treatment was 7.2 +/- 0.4 hours. In five patients on long-term carbamazepine treatment the half life was 8.4 +/- 1.4 hours. In four patients on combined diphenylhydantoin and carbamazepine treatment the half life was 7.4 +/- 0.7 hours. All these were significantly shorter than a mean half life of 15.1 +/- 1.0 hours when doxycycline was given to nine control patients. Therefore doxycycline in normal doses given to patients taking diphenylhydantoin or carbamazepine may fail to maintain the minimum inhibitory concentration necessary for proper bacteriostasis. When doxycycline is given in association with agents known to induce drug metabolism the serum concentration of the antibiotic should be watched to see that bacteriostatic levels are maintained.

Adult↗