1. Plasma phenytoin (diphenylhydantoin) levels after different drug doses were correlated with urinary 5-(p-hydroxyphenyl)-5-phenylhydantoin (p-HPPH) excretions in four subjects. 2. In three of four subjects the proportion of the phenytoin dose that was excreted as p-HPPH. In the fourth, p-HPPH output remained proportionate to dose of phenytoin until elimination of the drug fell below its input. 3. Plasma p-HPPH levels were measured in two subjects; the data suggested that the renal excretion of p-HPPH was not rate-limited. 4. In three of four subjects, there was the possibility that alternative pathways for eliminating phenytoin may have developed as drug doses increased and the capacity for forming p-HPPH became saturated. 5. Overall phenytoin elimination appeared to approach saturation at concentrations of the drug encountered therapeutically. When Michaelis-Menten kinetics were applied to data for phenytoin elimination in twenty-one adults and fifteen children, the mean apparent Km value for the adults corresponded to a plasma drug concentration of 5-8 mug/ml, and in the children to 5-3 mug/ml. The mean Vmax values in the two groups were, respectively 8-1 mg/kg per day and 12-5 mg/kg per day.

Adolescent↗

PubMedDate not supplied

The comparative bioavailability of carbamazepine in 100 mg and 200 mg tablets.

1. The bioavailabilities of carbamazepine in 100 mg and 200 mg tablets have been compared in a cross-over study of six subjects after two 600 mg doses of the drug, the different preparations being taken at 3 week intervals. 2. Areas under the plasma level curves, absorption rate constants and times to achieve peak plasma levels showed little difference between the two preparations. These findings suggest similar rates and extents of bioavailability of carbamazepine in the two preparations. 3. Calculated mean absorption and elimination parameters for carbamazepine were as follows: kabs = 0.1081 h-1, (s.d. = 0.0289); Tmax = 23.39 h, (s.d. = 8.66); k = 0.0191 h-1, (s.d. = 0.0033); VD = 0.989 1/kg, (s.d. = 0.159); and clearance = 0.0185 1/kg h, (s.d. = 0.0015).

Adult↗

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↗

PubMedDate not supplied

Factors influencing plasma concentrations of ethosuximide.

The relation between steady-state plasma ethosuximide level and drug dose was studied in 46 patients. In this population, plasma drug levels were proportional to drug dose, expressed on a body weight basis. Age did not alter this relationship, but plasma levels increased more rapidly, relative to dose, in females than in males. Intake of methylphenobarbitone, but not intake of certain other anticonvulsants (phenytoin, phenobarbitone, primidone and carbamazepine) altered the relationship between plasma ethosuximide level and ethosuximide dose. In individual patients, successive dose increments of equal size produced progressively greater increases in steady-state plasma ethosuximide levels. This phenomenon has obvious therapeutic implications.

Adolescent↗