Few data exist in the literature to support the use of high dosages of oral baclofen and clonidine that are frequently required to treat children with spasticity. This study was a retrospective chart review of baclofen and clonidine dosages used in children diagnosed with cerebral palsy or traumatic brain injury. The primary objective was to calculate the mean dosages of baclofen and clonidine based on the duration of spasticity postinjury. Secondary objectives included determining correlations between dosage and age, injury type, location of spasticity, comorbid seizures, or concomitant antispasticity medications. Eighty-seven children receiving baclofen and/or clonidine were included in this study. Mean dosages of 40 mg/day ( n = 86) and 0.4 mg/day ( n = 31) were required for baclofen and clonidine, respectively. The maximum dosage was 240 mg/day for baclofen and 3.6 mg/day for clonidine. Duration postinjury, age, and concomitant antispasticity medications were the most predictive variables for baclofen dosage as a model ( r = .522; P = .000). Duration postinjury and location of spasticity were the most predictive variables for clonidine dosage as a model ( r = .523; P = .000). The average dosages of baclofen and clonidine used in this population of children with cerebral palsy or traumatic brain injury were similar to those reported in the literature, with higher maximum dosages found in this investigation.
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.
Intravenous vitamin E was associated with the deaths of 38 infants in the US in 1984. Because the vitamin E preparation used contained both vitamin E and a high level of polysorbate detergent, the etiology of the syndrome remains unknown. In this study, we determined the tissue disposition of an intravenous preparation of vitamin E solubilized with polysorbate (E-Ferol) in neonatal piglets. One to two-day-old piglets were injected daily with 50 IU/kg/d of vitamin E for a period of 13 days. Other groups were injected intramuscularly, or with a slow, 7 h intravenous infusion with 50 IU/kg/d vitamin E for six days. Massive splenic accumulation of vitamin E (16,004 micrograms/g vs 73 micrograms/g in controls) occurred following rapid injection, with far lesser concentrations in the liver and lung. Levels of vitamin E in the kidney and heart were only slightly above control. Tissue changes correlated with dosage and duration of vitamin E administration and suggested massive accumulation of vitamin E in cells of the mononuclear phagocyte system. Following slow intravenous infusion the highest levels of vitamin E occurred in the liver rather than spleen. Intramuscular injections at similar doses produced slight, but insignificant changes in tissue levels of vitamin E. We speculate that rapid intravenous injection of vitamin E emulsions produces massive accumulation in phagocytic cells of the spleen and to a lesser extent liver and lung, possibly leading to increased susceptibility to sepsis and/or abnormal pulmonary function. Slow infusions of vitamin E produce major accumulations in the liver rather than spleen.(ABSTRACT TRUNCATED AT 250 WORDS)
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.