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Biomedical subjects

R Lucek

Publications and source records attributed to R Lucek.

9 recordsLinked to original sources
PubMed1982

Midazolam: radioimmunoassay for pharmacokinetic studies in man.

A specific radioimmunoassay (RIA) for the determination of the new short-acting water soluble imidazo-1,4-benzodiazepine, midazolam, directly in plasma has been developed. Employing 3H-midazolam as the radioligand and a rabbit antiserum to a diazo conjugate of 5'-aminomidazolam and albumin, the method has a limit of sensitivity of 2 ng/ml of midazolam using a 20 microliters sample of plasma. The intra- and inter-assay coefficients of variation ranged from 4 to 7% and 13 to 15%, respectively. The specificity of the RIA was established by demonstrating good agreement with both EC-GC and GC-MS procedures in the analysis of multiple clinical plasma samples. The utility of the RIA for the pharmacokinetic evaluation of midazolam is illustrated with plasma concentration profiles of the drug obtained in subjects who had received midazolam intravenously, intramuscularly and orally.

Animals↗
PubMed1980

Influence of phenytoin and phenobarbital on the disposition of a single oral dose of clonazepam.

Clonazepam (CZP) was measured in the plasma of eight subjects for 48 hr after a 0.03-mg/kg oral dose. After pretreatment for 19 days with phenytoin (DPH, 4.3 mg/kg/day), plasma CZP concentrations were determined in the same subjects after another 0.03 mg/kg oral dose of CZP. The same protocol was followed in eight additional subjects using phenobarbital (PB, 1.4 mg/kg/day) instead of DPH. DPH pretreatment lowered mean plasma CZP concentration in 8 of the 12 time points. DPH pretreatment increased CZP clearance by 46% to 58% and decreased CZP half-life (t1/2) by 31%. Both changes were statistically significant. After PB pretreatment the mean plasma CZP concentration was lowered by an average of 11%, but the decrease was statistically significant for only 1 of the 12 time points. PB decreased mean CZP t1/2 by 11% and increased CZP clearance by 19% to 24%, but only the increase in clearance was statistically significant. Both DPH and PB increased CZP clearances and decreased the areas under the plasma concentration-time curves without altering the volumes of distribution. This observation is consistent with induction of CZP metabolism. The overall effect of DPH (4.3 mg/kg/day) was greater than the effect of PB (1.4 mg/kg/day). Neither the DPH or PB had a significant effect on the extent of CZP protein binding.

Adult↗
PubMed1980

Chlordiazepoxide concentrations in saliva and plasma measured by radioimmunoassay.

A new, sensitive and specific radioimmunoassay (RIA) for chlordiazepoxide was used to determine concentrations of the drug in microsamples of saliva and plasma obtained from subjects following intravenous and oral administration of the drug. Saliva and plasma concentrations of the drug were highly correlated (r = 0.95) and the saliva/plasma ratio had a mean value of about 0.03. Saliva levels of chlordiazepoxide were found to be equal to the concentration of unbound drug in the plasma. Drug half-lives determined from both plasma and saliva concentration-time curves were found to be equivalent.

Chlordiazepoxide↗
PubMed1980

Radioimmunoassay and plasma concentrations of the anti-allergenic agent, 2-methoxy-11-oxo-11-H-pyrido[2,1-b]quinazoline-8-carboxylic acid in man.

A specific radioimmunoassay (RIA) for the determination of the antiallergenic agent, 2-methoxy-11-oxo-11H-pyrido[2,1-b]quinazoline-8-carboxylic acid (I), directly in plasma has been developed employing a rabbit antiserum to an albumin conjugate of I. The RIA has a limit of sensitivity of 0.4 ng/ml of I using a 0.1 ml sample of plasma. The intra- and interassay coefficients of variation did not exceed 6 and 9%, respectively. The specificity of the RIA was established by comparison with a less sensitive high-performance liquid chromatographic procedure and excellent agreement (r = 0.98) was observed when plasma samples were assayed by both methods. The RIA was used to determine plasma concentrations of I in man, for the first time, following oral administration of single 2, 10 and 50 mg doses of the drug.

Adult↗
PubMed1977

Specific radioimmunoassay for amitriptyline and nortriptyline in plasma.

A specific radioimmunoassay (RIA) for the determination in plasma of the widely used tricyclic antidepressant amitriptyline (AT) and its major metabolite nortriptyline (NT) has been developed employing 3H-AT as the radioligand and a rabbit antiserum to a bovine serum albumin conjugate of N-succinyl-nortriptyline. Although the antiserum cross-reacts almost equally well with AT and NT, specificity is achieved by selective extraction of each compound from plasma at a different pH. A unique aspect of the assay is that at no time during the entire extraction procedure is the AT or NT taken out of solution. Both compounds are back extracted from the organic phase into 0.1 N HC1 and the acid fraction subjected to RIA directly. The method has a limit of sensitivity of about 2 ng/ml using a 0.5 ml sample of plasma. Satisfactory agreement was obtained for plasma levels of AT and NT when determined by the RIA and a specific GC/MS procedure. The correlation coefficients were 0.89 and 0.98 for AT and NT, respectively. THE RIA has been used to measure steady-state levels of AT and NT in man after chronic administration of AT and following a single oral 75 mg dose. The method also lends itself for the specific determination of NT alone in subjects receiving therapeutic doses of NT.

Amitriptyline↗