PubMed Health⌕ Search

Biomedical subjects

L Lansky

Publications and source records attributed to L Lansky.

11 recordsLinked to original sources

Kinetics of primidone metabolism and excretion in children.

The metabolism and excretion of orally administered primidone was studied in 12 children, aged 7 to 14 yr during long-term dosing. Plasma concentrations of primidone (Pr) peaked at 4 to 6 hr and declined exponentially from 6 to 24 hr, with half-life (t1/2) values ranging from 4.5 to 11 hr. A mean of 92% (72% to 123%) of the administered dose was recovered within 24 hr from the urine as Pr and its metabolites. Of the total Pr daily dose, 42.3% (15.2% to 65.9%) was recovered as unchanged drug, 45.2% (16.3% to 65.3%) as phenylethylmalonamide (PEMA), and 4.9% (1.1% to 8.0%) as phenobarbital (Pb). The mean rate constant for conversion of Pr to PEMA (K1) was 0.0424 hr-1, for conversion of Pr to Pb (K2) was 0.0045 hr-1, and for excretion of unchanged Pr (K3) was 0.0389 hr-1. Of Pb excreted, 43% (13% to 100%) was unchanged, 15% (0% to 27%) was unconjugated p-OH Pb, 20% (0% to 44%) was conjugated p-OH Pb, and 22% (0% to 33%) was conjugated 3,4-OH Pb. KE appears to be important determinant of the steady-state plasma concentration of Pb, but interindividual differences in K2 have little influence on the overall rate constant for elimination of Pr.

Adolescent↗

Transiently reduced activity of carbamyl phosphate synthetase and ornithine transcarbamylase in liver of children with Reye's syndrome.

Since Reye's syndrome is associated with hyperammonemia, we measured the urea-cycle enzymes in hepatic tissue of 13 patients. Expressed as nanomoles of citrulline per milligram of hepatic protein per minute, mean activity of carbamyl phosphate synthetase (6.27 +/- 2.45 S.D.) and ornithine transcarbamylase (136.19 +/- 41.83) in Reye's syndrome was reduced significantly (P less than 0.005) when compared with that of 25 "normal" controls (11.54 +/- 4.24 and 307.49 +/- 94.15, respectively). Activity was maximally reduced during the first days of clinical symptoms; it returned toward normal during the following week regardless of whether the disease ended in death or recovery. The activity of the two enzymes was normal in patients with salicylate intoxication or heritable argininosuccinic acid synthetase deficiency. The apparent Km of hepatic ornithine transcarbamylase for ornithine was in the normal range in patients with Reye's syndrome (mean 0.24 mM). These observations indicate that Reye's syndrome is associated with acquired and transient dysfunction of hepatic mitochondrial urea-cycle enzymes.

Age Factors↗