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Biomedical subjects

J M Pellock

Publications and source records attributed to J M Pellock.

98 records · Page 6Linked to original sources
PubMedDate not supplied

Effect of two administration schedules of an enteral nutrient formula on phenytoin bioavailability.

Continuous nasogastric (NG) administration of enteral nutrient formulas (ENFs) reportedly lowers phenytoin (PHT) concentrations. We studied the effects of two administration schedules of an ENF on the bioavailability of PHT. Eight healthy volunteers received 400 mg PHT suspension after fasting (A), with hourly Ensure (B), and with 4-hourly Ensure (C) in a randomized, crossover design. Data obtained from 13 serum samples collected over 80 h were analyzed using ESTRIP. Area under the serum concentration-time curve (AUC), time to maximum serum concentration (Tmax), and urinary excretion of 5-(p-hydroxyphenyl) 5-phenylhydantoin (HPPH) were compared by analysis of variance (ANOVA) and Bonferroni t tests of differences between means. AUCs (mg x h/L) were not different (p greater than 0.05) for A (222.1 +/- 86.9), B (233.9 +/- 92.9), and C (226.0 +/- 95.7). Tmax (h) was significantly shorter (p less than 0.05) when PHT was administered with Ensure (B = 8.5 +/- 3.0, C = 5.3 +/- 2.0) than without Ensure (A = 18.5 +/- 10.5). The HPPH excretion (mg/80 h) was not different (p greater than 0.05) for A (225.6 +/- 48.5), B (238.6 +/- 26.6), and C (229.9 +/- 45.6). Clearance and maximum concentration correlated with AUC, obviating the need for analysis. Relative bioavailability was B/A = 1.07 +/- 0.21, C/A = 1.01 +/- 0.14. The bioavailability of PHT was not decreased by either ENF administration schedule. Factors other than direct contact may be responsible for the observed decreases in PHT concentrations by coadministered ENFs.

Administration, Oral↗
PubMedDate not supplied

Determinants of mortality in status epilepticus.

Using univariate and multivariate regression analysis, we studied seizure duration, seizure type, age, etiologies, other clinical features, and mortality among 253 adults with status epilepticus (SE) admitted to the Medical College of Virginia. Cerebral vascular disease and discontinuation of antiepileptic drugs (AEDs) were the most prominent causes of SE, each accounting for approximately 22% of all patients in the series. The other principle etiologies were alcohol withdrawal, idiopathic, anoxia, metabolic disorders, hemorrhage, infection, tumor, drug overdose, and trauma. When the patients were divided into two groups, the group with SE lasting < 1 h had a lower mortality as compared with seizure duration > or = 1 h. Low mortality rates were noted in alcohol and AED discontinuation etiologies. Anoxia and increasing age were significantly correlated with higher mortality. The mortality rates of partial and generalized SE were not significantly different. Race and sex did not affect mortality significantly. Our findings represent the first multivariate analysis of predictive indicators of mortality in SE and demonstrate that specific factors influence mortality rate in SE.

Adolescent↗
PubMedDate not supplied

Lamotrigine therapy for partial seizures: a multicenter, placebo-controlled, double-blind, cross-over trial.

The efficacy and safety of lamotrigine (LTG), a new antiepileptic drug (AED), were evaluated in a multicenter, randomized, double-blind, placebo-controlled, cross-over study of 98 patients with refractory partial seizures. Each treatment period lasted 14 weeks. Most patients were titrated to a LTG maintenance dose of 400 mg/day. Seizure frequency with LTG decreased by > or = 50%, as compared with placebo, in one fifth of patients. Overall median seizure frequency decreased by 25% with LTG as compared with placebo (p < 0.001). With LTG, the number of seizure days decreased by 18% as compared with placebo (p < 0.01), and investigator global evaluation of overall patient clinical status favored LTG by 2:1 (p = 0.013). Plasma LTG concentrations appeared to be linearly related to dosage. LTG had no clinically important effects on the plasma concentrations of concomitant AEDs. Adverse experiences were generally minor and most frequently were CNS-related (e.g., ataxia, dizziness, diplopia, headache). Most were transient and resolved without discontinuing treatment. Five patients withdrew as a result of adverse experiences while receiving LTG, including 3 patients with rash. One placebo patient was also withdrawn because of rash. The addition of twice-daily LTG to an existing AED regimen was safe, effective, and well tolerated in these medically refractory partial seizure patients.

Adult↗
PubMedDate not supplied

Risk-benefit assessment of carbamazepine in children.

Carbamazepine is an effective antiepileptic drug for the treatment of partial and convulsive generalised epilepsy in adults and children. The pharmacokinetic profile in children is similar to that in adults, but the half-life in long term paediatric therapy is between 6 and 12 hours, compared with 15 hours in adults. Autoinduction is present. The most common adverse effects are neurological and dose-related, and occur in up to 50% of patients treated, usually on dosage initiation or dose elevation. Most dissipate over time and require no alteration in dosage. Idiosyncratic effects include hypersensitivity, hepatic and haematological reactions. A benign leucopenia occurs in 10 to 12% of adults and children and appears to be unrelated to aplastic anaemia which occurs in approximately 1 in 575,000 treated patients per year. Carbamazepine is reported to have cognitive and behavioural advantages over other antiepileptic drugs. Overall, carbamazepine has become a major antiepileptic drug in children as well as adults.

Abnormalities, Drug-Induced↗
PubMedDate not supplied

Single-dose model for predicting steady-state valproic acid serum concentrations in seizure patients.

Valproic acid serum concentrations predicted by a single-dose prediction model were compared with steady-state serum concentrations measured after the start of therapy in seizure patients. Ten patients receiving valproic acid for the first time or who had not been taking the drug for two or more weeks were entered into the study. The patients' therapies were initiated with the prescribed doses of valproic acid and then maintained on fixed doses and dosing intervals until steady-state trough serum samples were obtained. Initial 5-ml blood samples were collected six to 14 hours after the ingestion of the first dose; a 5-ml steady-state trough sample was drawn in the same manner three to seven days later. Both free and total drug concentrations were determined within 48 hours of sample collection using gas-liquid chromatography. The elimination rate constant was estimated from age-specific population half-life values found in the literature. Six patients (five children, aged four to 16 years) and one adult (aged 87 years) completed the study. There was a statistically significant correlation between predicted and measured steady-state valproic acid serum concentrations for both free and total concentrations. The single-dose prediction model accurately predicted steady-state valproic acid serum concentrations in these seizure patients.

Adolescent↗
PubMedDate not supplied

Effects of three antacids on the bioavailability of valproic acid.

The effects of three antacid products on the bioavailability of valproic acid were evaluated. Each of seven normal, healthy volunteers received a 500-mg dose of valproic acid alone on one occasion and then with each of three commonly used antacids. Specifically, equal neutralizing capacity doses of 160 meq of Maalox (62 ml), Trisogel (97 ml), or Titralac (42 ml) were administered one and three hours after meals and at bedtime on the same day. Blood samples were obtained at 0, 1, 2, 4, 6, 8, 10, 24, and 32 hours and analyzed for valproic acid by gas liquid chromatography. There was a significant increase in total area under the curve (AUC) (range 3% to 28%, mean 12%) when valproic acid was administered with Maalox (p = 0.026 for total AUC and p = 0.009 for AUC to 32 hours). There was an insignificant trend toward an increase in AUC when valproic acid was administered with the other two antacids. No differences were observed in time to peak serum concentration, height of peak serum concentration, volume of distribution, half-life, or first order elimination rate constant. Caution should be exercised if valproic acid and antacids are administered concomitantly.

Adult↗