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Biomedical subjects

C M Lander

Publications and source records attributed to C M Lander.

28 records · Page 2Linked to original sources
PubMed1977

Factors influencing plasma phenobarbitone levels in epileptic patients.

1 Various statistical techniques were used to study the effects of age, sex and concurrent therapy with other anticonvulsants on the relation between plasma phenobarbitone levels and doses of (i) phenobarbtione, (ii) methylphenobarbitone or (iii) primidone, in epileptic patients. 2 Methylphenobarbitone and primidone are converted to phenobarbitone in the body. The mean doses of phenobarbitone, methylphenobarbitone and primidone which produced the same plasma phenobarbitone level (15 microgram/ml) were, respectively, 1.75,2.75 and 7.75 mg kg-1 day-1. 3 For both phenobarbitone and methylphenobarbitone dose requirement to achieve a given plasma phenobarbitone level fell progressively with age. Sex influenced the relation between plasma phenobarbitone level and phenobarbitone or methylphenobarbitone dose. Interactions were detected between primidone and both phenytoin and carbamazepine. 4 In individual patients, within the limits of dosage studied, the relation between plasma phenobarbitone level and drug dose was not rectilinear if phenobarbitone itself was taken, but was rectilinear if methylphenobarbitone was taken.

Adolescent↗
PubMed1977

Plasma anticonvulsant concentrations during pregnancy.

Plasma anticonvulsant levels were followed during pregnancy in 11 epileptic women taking phenytoin and/or phenobarbital or a drug metabolized in the body to phenobarbital. As judged from the relationship between plasma level and drug dose, phenytoin requirement increased in all 10 women taking this drug during pregnancy. The requirement fell again in the puerperium. Plasma phenobarbital levels decreased during pregnancy in all five women taking a constant daily dose of phenobarbital or a congener. These findings should be borne in mind if epileptics are to be protected against seizures during pregnancy and against anticonvulsant overdosage during the puerperium.

Epilepsy↗
PubMed1977

Factors influencing plasma carbamazepine concentrations.

Steady-state plasma carbamazepine levels were correlated with carbamazepine dose, expressed on a body weight basis, in 217 patients (some of whom were taking other anticonvulsants). Although there was a linear relation between plasma carbamazepine level and drug dose in the whole population studied, no such relation was found for patients taking carbamazepine alone. The factors responsible for this difference could not be identified in full, but interactions between carbamazepine and phenytoin were partly responsible.

Adolescent↗
PubMed1976

Hereditary motor peripheral neuropathy predominantly affecting the arms.

A kinship is described in which there was slowly progressive wasting and weakness of the muscles of the upper and occasionally of the lower limbs. Some members had hyperreflexia. There were no sensory abnormalities. Electrophysiological study suggested the presence of motor peripheral polyneuropathy. The condition appeared to be inherited as an autosomal dominant. The disorder does not appear typical of any of the known hereditary polyneuropathies and it is possible that it may represent a unique hereditary, dominantly motor, polyneuropathy. The significance of the hyperreflexia is uncertain, but raises the possibility of minor central involvement as well as peripheral neuropathy.

Adolescent↗
PubMed1976

The effects of phenobarbitone dose on plasma phenobarbitone levels in epileptic patients.

The relation between plasma phenobarbitone level and phenobarbitone dose was studied in 121 patients. The relation changed with age, the dosage requirement (on a day weight basis) tending to fall as patients grew older. Males under 5 years had a higher dosage requirement than females of the same age, but otherwise sex did not affect the relationship, nor did the concurrent intake of the anticonvulsants phenytoin, carbamazepine or sulthiame. In the individual, plasma phenobarbitone levels tended to increase out of proportion of dosage increases. These findings can provide a basis for prescribing appropriate phenobarbitone doses in epileptics.

Adolescent↗
PubMed1975

Interactions between anticonvulsants.

Anticonvulsant drug interactions have been investigated using multiple linear regression analyses. The one statistically significant interaction found was that in which phenytoin dosage decreased plasma carbamazepine concentrations. There was a suggestion that carbamazepine and phenobarb dosage tended to increase phenytoin levels. No interaction was detected between phenytoin and sulthiame. Studies in individuals suggested that ethosuximide may increase plasma phenytoin concentration and that clonazepam tends to decrease carbamazepine and phenytoin concentrations.

Anticonvulsants↗
PubMedDate not supplied

Antiepileptic drug intake during pregnancy and malformed offspring.

Possible associations between the presence of malformations in the offspring and various factors related to epilepsy were studied in 134 pregnancies in 105 epileptic women who had plasma antiepileptic drug concentrations measured on multiple occasions during pregnancy. No statistically significant associations could be detected between the malformations and maternal age, the number of the pregnancy, the type, duration or activity of the maternal seizure disorder, and the nature, dose or maximum recorded plasma concentration of the antiepileptic drugs used in the first 16 weeks of pregnancy. However, there was a statistically significant association between the malformations and maternal intake of antiepileptic drugs in combination. No particular combination of agents could be shown responsible for the association, which has been noted previously in the literature. It seems that a much larger study will be needed to clarify the matter.

Abnormalities, Drug-Induced↗
PubMedDate not supplied

Plasma antiepileptic drug concentrations during pregnancy.

Steady-state plasma antiepileptic drug (AED) concentrations were measured at intervals throughout pregnancy and during the postnatal period in 105 women who underwent 134 pregnancies. Phenytoin (PHT) dosage had to be increased in 85% of pregnancies in which the drug was received, carbamazepine (CBZ) dosage in 70%, and phenobarbital (PB) or methylphenobarbital (MPB) dosage in 85%, in an attempt to prevent or correct a fall in plasma concentrations of the respective drugs as pregnancy progressed. The altered disposition of the AEDs usually began in the first 10 weeks of pregnancy (often before epileptic pregnant women are referred for neurological supervision), and had returned to baseline value within 4 weeks of childbirth in two thirds of the women receiving PHT. The return to the nonpregnant situation appeared to be slower for CBZ, PB, and MPB. In women studied during more than one pregnancy, the changes in AED dosage to plasma concentration ratios tended to be greater in the first than in the subsequent pregnancies. Full seizure control prior to pregnancy was associated with a more favorable outcome for freedom from seizures during pregnancy. However, the plasma level monitoring-dosage adjustment policy produced no marked improvement in overall seizure control in pregnancy. This may have occurred because some patients were seen too late in their pregnancies for the policy to have been applied optimally.

Adolescent↗
PubMedDate not supplied

Plasma drug level monitoring in pregnancy.

During pregnancy a number of continuously changing circumstances exist which might be expected to modify the relation between plasma drug levels and drug dosage. Alimentary tract motility may be decreased, the distribution of many drugs may be altered, glomerular filtration rate is greater and biotransformation capacity may be changed as pregnancy advances. However, relatively little has been published on the monitoring of plasma drug levels during pregnancy. It has been established that, in the presence of constant drug doses, plasma levels of phenytoin, phenobarbitone and certain other anticonvulsants tend to fall during pregnancy and rise again during the puerperium. Plasma lithium and possibly digoxin levels also fall relative to drug dose as pregnancy progress, and rise again in the puerperium. While the changes in lithium and digoxin levels are probably chiefly due to increased rate of glomerular filtration during pregnancy, the altered anticonvulsant requirement is more likely to depend mainly on an increased rate of biotransformation. Anticonvulsant plasma levels should be monitored regularly from the outset of pregnancy and more frequently after birth.

Anticonvulsants↗