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M Rowland

Publications and source records attributed to M Rowland.

At least 217 records · Page 12Linked to original sources
PubMed1982

Further considerations of the "single-point single-dose" method to estimate individual maintenance dosage requirements.

The "single-point, single-dose" method for predicting individual maintenance dosage is examined. Data available in the literature on nortriptyline is used to illustrate the method. Optimal use of the method requires knowledge of the pharmacokinetics, especially the elimination rate constant, within the patient population requiring the drug. The method is applicable to intravenous and extravascular administration, when absorption is rapid relative to elimination, for those drugs whose disposition kinetics can be described by a linear one-compartment model. As a reasonable approximation, the optimal sampling time after the single test dose is 1.5 times the population half-life. Error in chemical analysis needs to be considered when applying the method. One method of evaluating the prediction and subsequent adjustment of dosage is discussed.

Half-Life↗
PubMed1981

Kinetics of drug displacement interactions.

A simple model simulating the kinetics of drugs displacement kinetics is investigated. It is demonstrated that for highly bound, lowly cleared drugs, displacement interactions are transitory. Consequently, the kinetics of the interaction have to be considered as well as the in vitro interaction. It is possible to have a significant in vitro displacement interaction with no in vivo counterpart. Methods of moderating drug displacement by adjusting the rate and the timing of administration of the displacing agent are discussed.

Binding, Competitive↗
PubMed1981

A chronic dose-ranging study of the pharmacokinetics of phenylbutazone in rheumatoid arthritic patients.

Phenylbutazone in doses of 200, 300 and 400 mg/day was administered chronically to six rheumatoid arthritic patients. At each steady-state the plasma levels of phenylbutazone, oxyphenbutazone and gamma-hydroxyphenylbutazone as well as the extents of binding of phenylbutazone and oxyphenbutazone to plasma proteins were measured. 2 Plasma concentrations of phenylbutazone did not increase proportionally with dose but when corrected for protein binding unbound concentrations of phenylbutazone did show a proportional increase with dose. 3 Plasma concentrations of oxyphenbutazone decreased with an increase in phenylbutazone dose suggesting either that the elimination of oxyphenbutazone is stimulated or its formation inhibited after chronic administration of phenylbutazone. 4 Binding studies with human serum albumin demonstrated the ability of phenylbutazone and oxyphenbutazone to mutually displace one another. Neither saturation of the protein binding sites nor displacement interactions could account for the changes in binding shown by phenylbutazone with increased dose. 5 gamma-hydroxyphenylbutazone concentrations increased proportionally with phenylbutazone dose reaching 68% of the phenylbutazone concentration in one patient. There was a large inter-subject variation in the gamma-hydroxyphenylbutazone concentrations.

Aged↗
PubMed1981

Acceptable sampling times at plateau for drug analysis.

1 Two methods of estimating the average plasma drug concentration at plateau Cav are considered. 2 Given an acceptable error in the estimate of Cav, a range of sampling times, rather than a single time, during the dosing interval, can be calculated. This range depends on the variability of the half-life within the patient population, the dosing interval, the error in assay measurement and the therapeutic index of the drug. 3 When the minimum plasma drug concentration is monitored, an estimate of the individual's half-life is needed, unless the dosing interval is short. Then the population half-life may be used to obtain a reasonable estimate of Cav.

Blood Specimen Collection↗
PubMed1980

Symbols in pharmacokinetics.

To encourage uniformity in the presentation of pharmacokinetic data, a general nomenclature has been developed. The system has wide application. Flexibility is achieved through the use of general variables, constants, qualifying terms, and subscripts. Yet, through the use of implied terms, the symbols describing many common variables and constants are simple.

Humans↗
PubMed1980

Aspirin binding and the effect of albumin on spontaneous and enzyme-catalysed hydrolysis.

A method of measuring the binding of aspirin to albumin without the interference of hydrolysis was developed. At concentrations of 10 mg litre-1, aspirin is about 85% bound to bovine serum albumin (4 g %), whereas its hydrolysis product, salicylic acid, is 95% bound. Salicylic acid was shown to displace aspirin from albumin binding sites. Both salicylic acid and aspirin bind more strongly to bovine serum albumin than to human serum albumin at protein concentrations of 4 g %. Protein binding protected aspirin against spontaneous hydrolysis although protein-bound aspirin still hydrolysed at a finite rate. In contrast, albumin enhanced the enzyme-catalysed hydrolysis of aspirin. By using a simple model, the rate constants for the individual processes contributing to the overall hydrolysis rate constant in the presence of albumin and esterase are calculated.

Animals↗
PubMed1980

Simultaneous liquid-chromatographic quantitation of salicylic acid, salicyluric acid, and gentisic acid in urine.

We have developed a specific and sensitive method for the determination of salicylic acid, salicyluric acid, and gentisic acid in urine. Any proteins present are precipitated with methyl cyanide. After centrifugation, an aliquot of the supernate is directly injected into an octadecyl silane reversed-phase chromatographic column, then eluted with a mixture of water, butanol, acetic acid, and sodium sulfate, and quantitated at 313 nm by ultraviolet detection according to peak-height ratios (with internal standard, o-methoxybenzoic acid) or peak heights (no internal standard). The method allows estimates within 25 min. Sensitivity was 0.2 mg/L for gentisic acid, and 0.5 mg/L for both salicyluric and salicylic acid (20-micro L injection volume); response was linear with concentration to at least 2.000 g/L for salicylic acid and metabolites. Analytical recovery of salicylic acid and metabolites from urine is complete. Intra-assay precision (coefficient of variation) is 5.52% at 7.5 mg/L for salicylic acid, 5.01% at 9.33 mg/L for salicyluric acid, and 3.07% at 7.96 mg/L for gentisic acid. Interassay precision is 7.32% at 7.51 mg/L for salicylic acid, 5.52% at 8.58 mg/L for salicyluric acid, and 3.97% at 8.32 mg/L for gentisic acid. We saw no significant interference in urine from patients being treated with various drugs other than aspirin.

Aspirin↗
PubMed1979

An in vitro study of drug displacement interactions: warfarin-salicylate and warfarin-phenylbutazone.

The binding interactions between warfarin-salicylate and warfarin-phenylbutazone in the presence of 4 g percent bovine serum albumin at 37 degrees C were studied using equilibrium dialysis. Methods of representing and analysing drug binding interactions are discussed. Scatchard plots, double reciprocal plots and the like are shown to be of no use in representing drug displacement interactions since they display only one drug and they can be potentially misleading. It is argued that a preferable method of analysing drug displacement interaction data is in terms of a stepwise multiple equilibria model. The numerical problems associated with fitting this kind of model to the data are discussed. A three-dimensional representation of the binding surface is proposed as a superior means of visualizing drug displacement interactions.

Animals↗
PubMed1977

Determination of phenylbutazone, tolbutamide and metabolites in plasma and urine using chemical ionization mass spectrometry.

Quantitative analytical procedures for the analysis of phenylbutazone and tolbutamide levels in plasma have been developed which involve the addition of deuterium labeled internal standards to plasma followed by extraction and direct sample insertion into a mass spectrometer operating under chemical ionization conditions. Peak height ratios used to calculate plasma levels were determined by using either selected ion monitoring or repetitive scan data. The scan approach was used in a related procedure for the simultaneous determination of tolbutamide and two metabolites from urine. The accuracy, precision and sensitivity of the direct sample insertion approach to drug level measurement has been determined. Examples are given of data obtained in the course of pharmacokinetic studies in which this analytical approach appears to offer advantages in the analysis of multicomponent mixtures encountered in drug-drug interaction studies.

Animals↗