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Biomedical subjects

L Hendeles

Publications and source records attributed to L Hendeles.

At least 91 records · Page 5Linked to original sources
PubMed1984

Preliminary study on the pharmacokinetics of phenobarbital in the neonatal foal.

Pharmacokinetic characteristics of the anticonvulsant phenobarbital were studied in seven pony and two Thoroughbred foals aged between four and 10 days. A single, 20 mg/kg bodyweight (bwt) dose of phenobarbital was given intravenously over 25 mins and the serum concentrations of the drug were measured using an EMIT AED assay (coefficient of variation 1.37 per cent at 30 micrograms/ml, n = 7). Phenobarbital elimination was found to follow first order kinetics. The mean (+/- sd) peak phenobarbital serum concentration was 18.6 +/- 2.1 micrograms/ml at 1 h after initiation of infusion with a mean (+/- se) half-life of 12.8 +/- 2.1 h. The mean (+/- se) volume of distribution was 0.86 +/- 0.026 litres/kg bwt and mean (+/- se) total body clearance was 0.0564 +/- 0.0065 litres/kg bwt/h. Sedation was noticed 15 to 20 mins after the beginning of infusion and lasted for up to 8 h. All foals could be aroused and could walk although they were ataxic for the first 1 to 2 h. A degree of delayed hyperexcitability occurred 3 to 8 h after infusion. In equine neonatal seizure disorders it is recommended to use a loading dose of 20 mg/kg bwt of phenobarbital, followed by maintenance doses of 9 mg/kg bwt at 8 h. With this regimen, average steady state serum phenobarbital concentrations should range between approximately 11.6 and 53 micrograms/ml. Phenobarbital serum concentrations should be monitored following the loading dose and 24 h after initiating the maintenance doses to check that levels remain within the suggested (human) therapeutic range of 15 to 40 micrograms/ml.

Animals↗
PubMed1984

Evaluation of a rapid immunoassay for monitoring serum pentobarbital concentrations.

A modification of the EMIT-Tox qualitative serum barbiturate assay (Syva Company, Palo Alto, CA) was evaluated for measuring pentobarbital concentrations. Pentobarbital calibrator solutions were substituted for the secobarbital calibrators provided with the assay kit, and control solutions of pentobarbital were used to determine the modified assay's precision and accuracy. Specificity for pentobarbital with respect to other barbiturates and assay interference from other drugs were evaluated in vitro. Serum samples obtained from 49 patients receiving intravenous pentobarbital sodium to treat intracranial hypertension were assayed by gas-liquid chromatography (GLC) and by the modified EMIT procedure. Samples from patients who were receiving both phenobarbital and pentobarbital (9 of 49) were assayed for both drugs, interference curves were plotted, and the corrected pentobarbital concentrations were compared with GLC values. The modified assay method provided an accurate measurement of serum pentobarbital concentrations of 1-30 micrograms/ml. Significant cross-reactivity with the pentobarbital assay was present for secobarbital, butabarbital, allobarbital, and phenobarbital. Dexamethasone, dopamine, phenytoin, cimetidine, lidocaine, diazepam, morphine, and several other drugs at concentrations of 1000 micrograms/ml did not interfere with the assay. There was a strong correlation between the GLC reference method and the modified EMIT assay (r = 0.96). Clinically important cross-reactivity with phenobarbital was found; the corrected pentobarbital concentrations for patients who had received phenobarbital strongly correlated with GLC results (r = 0.98). The modified assay appears to be sufficiently reliable for determination of pentobarbital serum concentrations.

Chromatography, Gas↗
PubMed1983

Effect of serum separator blood collection tubes on drug concentrations.

Using the EMIT assay, we tested clinical samples from patients receiving 12 commonly monitored drugs to evaluate the effect of serum separator gel contained in serum separator blood collection tubes (SST) (Becton-Dickinson). There were significant concentration decreases for lidocaine, pentobarbital, and phenytoin. In vitro experiments demonstrated that this effect on phenytoin was dependent on time of exposure to the gel and volume of whole blood, but was not dependent on the presence of red blood cells or initial concentration. Bias attributed to the use of SST could interfere with the usefulness of clinical results at the upper and lower limits of the therapeutic range. This problem can be minimized by processing samples of at least 2 ml within 1 h.

Blood Specimen Collection↗
PubMed1983

High intravenous phenytoin dosage requirement in a newborn infant.

A term neonate was being treated with intravenous phenytoin. To maintain a serum level above 10 micrograms per milliliter and abolish seizure activity, it was necessary to carry out repeated serum concentration measurements, administer several loading doses, and administer an unusually large maintenance dose (25 mg per kilogram per day), divided into a short dosing interval (6 hours). Declining serum levels from postnatal days 8 to 13 on a constant dose of 9 mg per kilogram per day suggested that the rate of phenytoin metabolism was gradually increasing; rapid elimination was documented on day 18 by a half-life measurement of 8.8 hours from three samples. The changing pharmacokinetics were attributed to maturation of oxidative metabolism of phenytoin, concurrent phenobarbital administration, or both. The need for additional loading doses and maintenance dose increases must be guided by serum concentration measurements to obtain maximum benefit with minimal risk of toxicity.

Female↗
PubMed1983

Theophylline for chronic asthma: rationale for treatment, product selection, and dosage schedule.

Although theophylline has been available for over 50 years, only in the last 10 years has an understanding of its pharmacodynamics and pharmacokinetics permitted its use with optimal efficacy and safety. Serum concentrations between 10 and 20 mcg/ml stabilize the hyperreactive airways that characterize asthma as measured by exercise-induced bronchospasm and clinical suppression of asthmatic symptoms, even among those patients not sufficiently controlled with bronchodilators alone who consequently require inhaled or oral corticosteroid therapy. Careful dosage titration prevents adverse effects, especially when final dosage is guided by measurement of serum concentration. Large interpatient variability in dose requirements is seen, but there is normally little intrapatient variability except when physiologic abnormalities or drug interactions alter the elimination of theophylline. Rapid elimination, rapid absorption from conventional products, and the narrow therapeutic range for theophylline result in clinically important fluctuations in serum concentration and consequent effect unless unrealistically short dosing intervals are maintained or reliable slow-release formulations are used. Slow-release theophylline products vary, however, and performance often does not match the manufacturer's claims. Assessment requires characterization of absorption rate, which then allows prediction of fluctuations in serum concentration at specified dose intervals and defined rates of elimination.

Adolescent↗
PubMed1982

Improved efficacy and safety of theophylline in the control of airways hyperreactivity.

Theophylline is a potent bronchodilator that can be effective as maintenance medication for preventing chronic symptoms of asthma. Benefit and risk of toxicity both relate directly to serum concentration, however, and large interpatient variability in rates of elimination require that dosage be individualized by measurement of serum concentration. Reliably absorbed slow-release formulations provide more stable blood levels for around-the-clock therapy and thus offer both convenience and major therapeutic advantage in stabilizing the hyperreactive airways that characterize chronic asthma.

Acute Disease↗