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Biomedical subjects

M Lund

Publications and source records attributed to M Lund.

At least 109 records · Page 6Linked to original sources

Pharmacokinetics and side-effects of clonazepam and its 7-amino-metabolite in man.

Clonazepam (CNP) and its principal metabolite in plasma, 7-amino-CNP (ACNP), have been investigated in a prospective study of 27 newly diagnosed epileptics and correlated with specified side-effects. At a daily dose of 6 mg, the average plasma levels of both substances were about 50ng/ml, and individual values ranged from 30 to about 80 ng/ml. There was a linear correlation between changes in dose and the resulting plasma levels, which indicates first order elimination kinetics. Side-effects were frequent, but neither their severity nor their occurrence could be related to plasma levels or to the rate of increase in plasma concentration of the drug. Three out of five patients who developed serious dysphoria had significantly high CNP levels. The concentration of ACNP was considerably increased in four patients who subsequently suffered from withdrawal symptoms. Drug interaction with diphenylhydantoin, i.e. decreased CNP level, was observed in all five patients who received both compounds. In general it is not yet possible to define an upper limit for the plasma levels of CNP and ACNP at which toxicity occurs. In patients treated with conventional doses of CNP, measurement of plasma concentration is not required, except in special circumstances, because of the lack of correlation between plasma level and side-effects.

Adolescent↗

A double blind study of carbamazepine and diphenylhydantoin in temporal lobe epilepsy.

In a double 0lind study no difference was found between carbamazepine and diphenylhydantoin with regard to efficacy in preventing temporal lobe seizures, i.e. partial seizures with complex symptomatology, when the drugs were given without other medication for periods of 16 weeks, and when the serum concentrations were within selected therapeutic levels corresponding to usual therapeutic dosage. Some patients, however, had considerably fewer seizures on carbamazepine, some on diphenylhydantoin. It therefore seems advisable to try both drugs separately, before using a combined medication.

Adolescent↗

A controlled trial on clonazepam INN (Ro 5-4023, Rivotril (R)) in the treatment of focal epilepsy and secondary generalized grand mal epilepsy.

In a controlled clinical investigation based on 14 patients with focal seizures and 3 patients with secondary generalized grand mal epilepsy, all with insufficient response to conventional anti-epileptic treatment, clonazepam (Rivotril(R)) combined with previous anti-epileotic drugs was compared with placebo combined with the same drugs. The trial was singleblind cross-over with sequential analyses. With a daily dose, depending upon age, of usually 3-6 mg, the antiepileptic effect of Clonazepam was significantly superior to placebo and was estimated as remarkably good. Side-effects in the form of somnolence, fatique, drowsiness and co-ordination disturbances occurred in most of the patients but subsided spontaneously or could be managed by slow increase or slight reduction in dosage.

Adolescent↗

Subjective symptoms in epileptic patients on anticonvulsant drugs. A controlled therapeutic trial on the effect of vitamin d.

The possibility (based on the recognised existence of anticonvulsant osteomalacia), of an osteomalacic origin of a number of subjective symptoms in epileptics (back pain, tiredness, sleepiness, irritability, and giddiness) was tested during a controlled therapeutic trial in 226 outpatients. There was no correlation between subjective symptoms and objective pathological indices of osteomalacia, and group treated with vitamin D (2000 international units daily for 3 months) showed no amelioration of subjective symptoms above that seen in the placebo group. The findings do not support the view that all epileptic patients on anticonvulsant therapy should be treated prophylactically with vitamin D.

Adult↗

Incidence of anticonvulsant osteomalacia and effect of vitamin D: controlled therapeutic trial.

The bone mineral content (B.M.C.) in both forearms (related to total body calcium) was measured by photon absorptiometry for a controlled therapeutic trial in a representative sample of epileptic outpatients, comprising 226 patients treated with one or two major anticonvulsant drugs (phenytoin, phenobarbitone, primidone).Initially the mean B.M.C. value for all epileptic patients was 87% of normal. During treatment with 2,000 international units of vitamin D(2) daily for three months an average B.M.C. increase of 4% was found, whereas the B.M.C. values remained unchanged in the placebo group and in the control groups. The incidence of hypocalcaemia and raised serum alkaline phosphatase was 12% and 43% respectively. The biochemical indices of osteomalacia were related to B.M.C. These results indicate that epileptic patients should be closely supervised for the occurrence of anticonvulsant osteomalacia, and, possibly, receive prophylactic treatment with vitamin D.

Adult↗

Effect of vitamin D on bone mineral mass in normal subjects and in epileptic patients on anticonvulsants: a controlled therapeutic trial.

The bone mineral mass was estimated by photon absorptiometry in 23 epileptic patients on long-term treatment with phenytoin and in 20 normal subjects before and during treatment with vitamin D or placebo.Initially, subnormal values of bone mineral mass were found in the epileptic patients. The group of epileptic patients treated with vitamin D showed a significant increase in bone mineral mass. The group of epileptic patients treated with placebo and the normal subjects treated with vitamin D or placebo showed no change in bone mineral mass.

Absorption↗