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Biomedical subjects

L Aarons

Publications and source records attributed to L Aarons.

At least 73 records · Page 4Linked to original sources
PubMed1987

Validation of assay methodology used in pharmacokinetic studies.

Statistical methods for validating assays used in pharmacokinetic studies are discussed. Methods for assessing linearity, variability, and sensitivity are derived. It is proposed that a calibration experiment, in which samples are replicated at three different concentrations, will provide the necessary information to validate an assay prior to commencement of a pharmacokinetic study and during its routine use. A two-stage weighted least squares regression is used to analyze the calibration data. High performance liquid chromatography calibration data are used to illustrate the principles and techniques involved.

Chromatography, High Pressure Liquid↗
PubMed1987

Enoxacin-warfarin interaction: pharmacokinetic and stereochemical aspects.

The interaction between the new quinoline-azaquinoline antibiotic enoxacin and the oral anticoagulant warfarin was investigated in six healthy male volunteers. Enoxacin was found not to affect the hypoprothrombinemic response produced by warfarin but did produce a decrease in the clearance of the less pharmacologically potent enantiomer of warfarin, (R)-warfarin. The decreased clearance of (R)-warfarin produced by concomitant enoxacin administration was found to be a consequence of inhibition by enoxacin of the (R)-6-hydroxywarfarin metabolic pathway.

Adult↗
PubMed1987

Pharmacokinetics of imipenem and cilastatin after their simultaneous administration to the elderly.

The pharmacokinetics of imipenem and cilastatin were studied in a group of six healthy elderly male volunteers following the combined intravenous administration of 500 mg imipenem and 500 mg cilastatin sodium as either single or multiple (6 hourly for 6 days) 20 min constant-rate infusions. The pharmacokinetics of both imipenem and cilastatin in the elderly were similar to those of young individuals with mild renal failure (Verpooten et al., 1984). There was no change in the pharmacokinetics of either species with time following multiple-dosing. Correlations existed between total clearance and the glomerular filtration-rate (51Cr-EDTA) for both imipenem and cilastatin.

Aged↗
PubMed1987

Inter-relationship among individual vitamin K-dependent clotting factors at different levels of anticoagulation.

1. The effect of subtherapeutic doses of warfarin on the activities of the four vitamin K-dependent clotting factors was studied at steady state in five patients each of whom had completed a therapeutic course of anticoagulation. 2. The four clotting factor activities were shown to be depressed to a similar extent for a given dose of warfarin. 3. The prothrombin complex activity was significantly lower than that of any of the clotting factors.

Aged↗
PubMed1987

Dose-dependent pharmacokinetics of cimetidine in the rat.

The pharmacokinetics of cimetidine were studied in the rat after intraperitoneal administration of 10, 40 and 100 mg/kg. The area under the plasma concentration-time curve increased more than proportionately with dose. The total plasma clearance of cimetidine decreased as the dose increased (4.11 to 2.21 l/h per kg) with a consequent increase in half-life (24.0 to 37.9 min) but no change in volume of distribution (mean 2.31 l/kg). The fraction of dose excreted unchanged increased slightly with dose (0.37 to 0.45), whereas the fraction excreted as the sulphoxide metabolite decreased significantly with increased dose (0.35 to 0.14). Both the renal clearance (1.52 to 0.99 l/h per kg) and the formation clearance of the sulphoxide metabolite (1.45 to 0.30 l/h per kg) decreased with increasing dose. Residual clearance, calculated as the difference between total clearance and the sum of renal and metabolic clearance, did not change with dose (mean 1.08 l/h per kg). The formation clearance of the sulphoxide metabolite became saturated at a lower cimetidine concentration than the renal clearance.

Animals↗
PubMed1986

Plasma and synovial fluid kinetics of flurbiprofen in rheumatoid arthritis.

Clinical assessment, plasma and synovial fluid kinetics were studied in 29 rheumatoid patients receiving 100 mg flurbiprofen twice daily. Clinical assessment and pharmacokinetic measurements varied widely within the group of patients. The average values for plasma clearance, volume of distribution and elimination halflife of flurbiprofen were 0.65 +/- 0.24 ml min-1 kg-1, 0.160 +/- 0.093 l kg-1 and 3.1 +/- 1.7 h, respectively. Synovial fluid drug concentrations peaked later and were lower than corresponding plasma concentrations: 5.2 h and 4.4 mg l-1 as against 1.49 h and 12.5 mg l-1, respectively. At 48 h after an oral dose of flurbiprofen, all the drug had been cleared from the synovial fluid. Synovial fluid drug concentrations were not related to synovial fluid albumin concentration or pH. There was a weak relationship between synovial fluid drug concentration and the thermographic measurements of disease activity. The fractions of flurbiprofen not bound to protein in synovial fluid and plasma were not significantly different. A simple model is proposed to account for the plasma and synovial fluid pharmacokinetics.

Adolescent↗
PubMed1985

The binding of flurbiprofen to plasma proteins.

The binding of flurbiprofen to human serum albumin and normal plasma was measured using ultracentrifugation. Flurbiprofen was bound in excess of 99% in all cases. Over the concentration range normally associated with therapy the data could be adequately described by a one-site binding model. The association constant decreased with increasing protein concentration, being 3.04 X 10(6) M-1 at an albumin concentration, of 2 g/100 ml and 1.19 X 10(6) M-1 at a concentration of 4 g/100 ml. Flurbiprofen binding showed no dependence on pH over the range 7.0 to 8.0.

Blood Proteins↗
PubMed1984

Amiodarone kinetics after single i.v. bolus and multiple dosing in healthy volunteers.

We studied three healthy volunteers after a single i.v. bolus of amiodarone, during 1 month of chronic oral dosing and after the discontinuation of the drug. Blood concentrations of amiodarone declined rapidly in a bi-exponential fashion after i.v. bolus. The terminal half-life ranged from 10 to 17 h; after discontinuation of chronic treatment the terminal half-lives were 8-21 days. The i.v. data, the trough levels during multiple dosing and the washout phase could be simultaneously fitted using a triexponential equation. The subjects were carefully monitored for cardiac and thyroid function. One subject had to stop taking amiodarone because of profound bradycardia. A reduction of serum TT3 and FT3 concentrations and an increase of serum rT3 and FT4 was found.

Adult↗
PubMed1984

General approach to handling nonuniform variance in assay calibration.

A general method for handling nonuniform variance in data from assay calibrations is discussed. Calibration data from the analysis of ibuprofen and aspirin by high-performance liquid chromatography was analysed by the traditional least squares method; nonuniform error variance was found to be significant. Weighted least squares analysis overcomes the problem of nonuniform variance but relies on good estimates of the error variance. The method of extended least squares, a maximum likelihood method, is described which incorporates handling of the weighting in the regression analysis. The extended least squares method produces accurate and precise estimates of the parameters of the calibration and allows precise estimates of the variance of future predictions, provided that a sufficient number of calibrators are used.

Journal Article↗
PubMed1983

Bioavailability of drugs with long elimination half-lives.

Methods for estimating the bioavailability of drugs with long elimination half-lives are examined. Provided both absorption and disposition are linear a simple linear regression method is developed which can be used to calculate bioavailability in situations where only an incomplete estimate of the area under the curve (AUC) is available. The regression method and the traditional method of comparing the AUC following an oral dose to the AUC following an i.v. dose were applied to simulated data. It was found that the AUC ratio method works well as long as absorption is complete within the time over which the AUC is computed. The regression method is less precise than the AUC ratio method but is more accurate for drugs with long absorption half-lives. When applied to published data on a beta blocker the two methods produced comparable results. The bioavailability of amiodarone in three human subjects was calculated to be 0.20, 0.44 and 0.98 using the regression method with similar results from the ratio method. It is not possible to estimate the clearance of amiodarone from single dose data.

Adrenergic beta-Antagonists↗
PubMed1983

The binding of ibuprofen to plasma proteins.

The binding of ibuprofen to human serum albumin, normal plasma and plasma obtained from rheumatoid arthritic patients was studied using the method of ultracentrifugation. It was found that ibuprofen is more strongly bound to normal plasma than to human serum albumin although this result is probably explained by fatty acid contamination of the human serum albumin. The fraction of ibuprofen not bound to normal plasma rose significantly from a value of 0.0128 at an ibuprofen concentration of 2 mg X l-1 to 0.0155 at a concentration of 50 mg X l-1. Ibuprofen was less strongly bound to rheumatoid plasma than to normal plasma but this difference can be accounted for by the difference in albumin concentration between the two plasmas. It was found that salicylic acid can displace ibuprofen from protein binding sites, in vitro, and that this is the probable cause of the pharmacokinetic interaction between the two drugs.

Arthritis, Rheumatoid↗