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Biomedical subjects

S I Johannessen

Publications and source records attributed to S I Johannessen.

At least 19 recordsLinked to original sources
PubMed1992

Pharmacokinetics of valproate in pregnancy: mother-foetus-newborn.

An increased risk of seizures during and immediately after labour has been observed in epileptic women, and it is recognized that serum levels of antiepileptic drugs may decrease in pregnancy. Several studies have suggested that total valproate levels fall, but that free fractions increase during pregnancy. Recent findings suggest that the actual metabolism of valproate is not altered by pregnancy and that the changes of the plasma clearance are due primarily to decreased protein binding. The levels of free drug will not change significantly as pregnancy advances. However, dose reduction after delivery may be necessary to avoid toxicity. Valproate and its metabolites undergo placental transfer. In the foetus the plasma level of valproate and the protein binding are higher than in maternal plasma, and the half-life of valproate following placental transfer is considerably longer than in adults. Only small amounts of valproate appear in breast milk and those are not likely to cause any problems. During pregnancy and the first month after delivery preferably both total and free valproate serum levels should be closely monitored to determine the lowest effective dose.

Anticonvulsants↗
PubMed1990

[Role of drug assays in the treatment of epileptic patients].

Drug assays play an important role in the control of antiepileptic treatment because the relationship between the serum concentration of an active drug and its therapeutic effects and side-effects is closer than between dose and effect. Bioavailability, protein binding and drug elimination are subject to inter- and intraindividual variations. However, it is important to remember that the optimal therapeutic ranges reported for serum levels are only a guideline to drug therapy. It is the patient who must be treated and not the serum level.

Age Factors↗
PubMed1982

Clinical and pharmacokinetic observations on sodium valproate - a 5-year follow-up study in 100 children with epilepsy.

Results of clinical and pharmacokinetic observations on sodium valproate (VPA) are reported from a long-term study in 100 children with epilepsy. VPA is the drug of choice in patients with absences. VPA may preferably be chosen as the first drug in patients with atonic seizures partly because all treatment of these seizures is uncertain, and the effect of VPA may be striking, without side effects. When starting with VPA the great problem of drug interactions is avoided. Treating patients with intractable epilepsy has shown that VPA may be effective in all seizure types regardless of the EEG-findings. However, generalized paroxysms of spike and wave complexes in the EEG are a good prognostic sign especially when fairly regular. Side effects are few when using enteric coated tablets, but toxic effects may be serious. Control schemes of blood and liver functions are necessary. Drug fasting serum level monitoring is mandatory, especially when VPA is given in combination with other anti-epileptic drugs as interactions with these are pronounced. Optimal clinical effect is usually seen on serum levels between 300 and 600 microgram mol/l, which may be obtained by giving 10-20 mg/kg daily assuming that the patient is receiving VPA monotherapy, which should always be aimed at. Comedication may have to be withdrawn to obtain therapeutic serum levels of VPA due to drug interactions.

Adolescent↗
PubMed1981

Influence of carbamazepine on serum thyroxine and triiodothyronine in patients with epilepsy.

Hypothyroidism induced by anti-epileptic drug treatment gave rise to thyroid function test studies in patients treated with carbamazepine (CBZ) only. In 42 patients on long-term CBZ treatment thyroxine (T4), free T4-index (FT4I), and triiodothyronine (T3) concentrations in serum were significantly lower than in controls, while triiodothyronine uptake (T3U) and thyrotropin (TSH) concentrations did not differ between patients and controls. In 12 patients starting on CBZ, means T4, calculated FT4 and thyroxine binding globulin (TBG) were 1-5 months later reduced compared to the initial levels. Thus, CBZ reduced thyroid hormones, TBG and FT4I. A CBZ-induced increase in conversion and metabolism of the thyroid hormones could explain this effect. The normal T3U values and decreased concentrations of TBG make a competitive CBZ binding to TBG less probable. Although the thyroid hormones levels were found lowered in the patients, all remained clinically euthyroid during the study.

Adolescent↗
PubMed1981

Antiepileptic drugs: pharmacokinetic and clinical aspects.

Serum level monitoring of antiepileptic drugs is important for an optimal drug therapy since relationships between serum levels and therapeutic and toxic effects have been clearly established for several drugs. Routine serum level monitoring based on pharmacokinetic and clinical knowledge has improved the treatment of epileptic patients. For routine determination of antiepileptic drugs, homogenous enzyme immunoassays offer several advantages over more complex techniques such as GLC and HPLC. Because of the speed of the analysis and the small sample volume, EMIT is the method of choice in many laboratories. A 50-microliter sample is sufficient for a single determination of up to five drugs. To ensure reliable results, quality control schemes are necessary regardless of the analytical technique utilized for drug quantitation. Routine monitoring of serum levels is especially important since drug bioavailability, as well as the rate of drug metabolism and excretion, varies widely among patients. Serum levels are also influenced by comedication. Changes in protein binding may also be of clinical importance under special circumstances. Active metabolites may contribute to the clinical effect of a drug. Correct dose frequency and standardized blood sampling time, preferably before the first morning drug dose, are also important factors for establishing optimal therapeutic regimens for a given patient. The serum levels of antiepileptic drugs should be determined when drug therapy is initiated, after dosage adjustments, in case of therapy failure, after addition of drugs which may cause drug interactions, when clinical signs of side effects or drug intoxication occur, and as a routine monitoring for patient compliance. Serum levels should be monitored if any change occurs in a patient's normal pharmacological state.

Age Factors↗
PubMed1980

Single-drug therapy with carbamazepine in patients with epilepsy: serum levels and clinical effect.

Carbamazepine (CBZ) was given as the only drug to 62 epileptic patients with mainly simple and complex partial seizures. Twenty-four of the patients were given CBZ as the only drug from the beginning of therapy, while 38 patients had formerly received other antiepileptic drugs. Serum concentrations of CBZ and CBZ-10,11-epoxide were determined by enzyme immunoassay and gas chromatography, respectively, in fasting morning blood specimens. Twenty of the 24 patients given CBZ from the beginning were seizure-free at follow-up 7-48 months later. These patients had a mean daily dose of CBZ of 7.5 (+/- 0.56) mg/kg and mean CBZ and epoxide serum concentrations of 23.4 (+/- 1.16) and 2.4 (+/- 0.20) mumoles/liter, respectively. The corresponding values for 25 of the 38 patients previously treated with other antiepileptic drugs were 10.3 +/- 0.66 mg/kg and 29.4 +/- 1.60 and 3.1 +/- 0.18 mumoles/liter. The follow-up in these patients was 11-58 months. Thirteen patients had poor seizure control, although they had serum CBZ and epoxide concentrations within the ranges giving seizure control in the rest of the patients. The concentrations of the epoxide in serum were significantly correlated to the concentrations of CBZ (r = 0.63, p < 0.01). The therapeutic range, 13-51 mumoles/liter, indicates great interindividual differences in optimal levels of CBZ. Accordingly, individually tailored drug regimens are necessary to achieve optimal therapeutic effects with CBZ.

Adolescent↗
PubMed1980

Serum of concentrations of immunoglobulins in patients with epilepsy treated with carbamazepine.

The concentrations of IgA, IgG and IgM were determined in sera of 16 patients, all of whom had partial epilepsy and had received CBZ as the only drug since the beginning of therapy. Fifty-three healthy subjects served as controls. Serum concentrations of IgA and IgG were significantly higher in patients than in controls (IgA: P = 0.05; IgG: P = 0.01). The concentration of IgM was not significantly different from that of the controls (P = 0.1). The IgG serum levels in the controls were lower with increasing age. Furthermore, IgG serum levels were higher with increasing CBZ concentrations.

Carbamazepine↗
PubMed1979

Comparative steady state serum levels of valproic acid administered as two different formulations--Deprakine and Orfiril.

Plain tablets of sodium valproate (VPA), a useful antiepileptic drug, are bitter tasting and produce gastric irritation which leads to poor patient compliance. We have studied the steady state serum levels of VPA which can be produced in epileptic patients before and after a 1 week treatment with a plain tablet (Deprakine) versus an enteric coated tablet (Orfiril). The latter drug produced in most patients a higher drug fasting blood level than the uncoated preparation (22%). The enteric coated tablets appeared also better tolerated.

Absorption↗
PubMed1978

Effect of carbamazepine, phenytoin and phenobarbitone on serum levels of thyroid hormones and thyrotropin in humans.

Patients on long-term treatment with either of the stereochemically related antiepileptic drugs phenytoin (DPH) or carbamazepine (CBZ) had similar changes in serum thyroid hormone concentrations. T4, FT4, FT4 index, T3, FT3, FT3 index and rT3 were reduced, whereas T3U and TSH were not significantly different from the reference group levels. Long-term phenobarbitone treatment had no convincing effect on the investigated parameters when used alone, but possibly potentiated the effect of CBZ. In patients starting on CBZ, T4 fell to a stable 70% of the basal level after 1--2 weeks. T3 decreased transitorily to 85% of the basal level. TSH showed a complementary but somewhat delayed transitory increase. T3U and TBG did not change significantly. The effect of CBZ and DPH can be explained by interference with thyroid hormone binding to TBG combined with enzyme-induced increased metabolic clearance rate of thyroid hormones without homeostatic maintenance of premedication levels of FT4 and FT3. We suggest that the regulated factor maintaining euthyroidism in these patients is the total quantity of thyroid hormones being degraded in the tissues per unit time. We conclude that serum concentrations of FT4 and FT3 do not reflect thyroid status adequately under all circumstances.

Adult↗
PubMed1977

Lack of effect of clonazepam on serum levels of diphenylhydantoin, phenobarbital and carbamazepine.

The influence of clonazepam on steady-state serum levels of diphenylhydantoin, phenobarbital and carbamazepine was studied in 22 patients with epilepsy receiving one or two of these drugs. Clonazepam was given in slowly increasing doses for 2 weeks until a maximum dose of 4-6 mg per day was reached; thereafter the dose was kept constant. The serum levels of diphenylhydantoin, phenobarbital and carbamazepine were determined once a week for at least 6 weeks. During clonazepam medication in ordinary doses the serum levels of the drugs in question were unaltered. Thus, it is unlikely that the antiepileptic effect of clonazepam in these patients even partly may be due to increased serum levels of these other drugs mentioned.

Adolescent↗
PubMed1977

Preliminary observations on valproic acid kinetics in patients with epilepsy.

A rapid gas chromatographic method for determination of sodium valproic acid (di-n-propylacetate, DPA) is described. A new sample can be injected every third min, and the reproducibility, in terms of the coefficient of variation, is better than 3%. The method has been used to study clinical pharmacokinetics of DPA in patients with epilepsy during long-term treatment. A poor correlation between daily dose (mg/kg) of DPA and steady state serum levels, attained within few days, was observed. A fixed sampling time in the individual patient, preferably before ingestion of the morning dose, is of great importance for DPA due to extended fluctuations of the serum levels during the day. Most patients had DPA serum levels in the order of 50 microng/ml. No constant relationship was found between increase of the dose and the corresponding increase of the serum levels. Interactions of clinical importance was observed between DPA and other antiepileptic drugs, as addition of DPA resulted in elevated serum levels of diphenylhydantoin and phenobarbital. Carbamazepine levels were unaltered. After withdrawal of DPA the half-life was about 14 h in adult patients. DPA levels in CSF were in the order of 10% of the corresponding serum levels.

Adult↗