Biomedical subjects

M K Charter

Publications and source records attributed to M K Charter.

5 recordsLinked to original sources

PubMed1991

Maximum entropy and drug absorption.

The application of maximum entropy to the calculation of drug absorption rates was introduced in an earlier paper. Here it is developed further, and the whole procedure is presented as a problem in scientific inference to be solved using Bayes' theorem. Blood samples do not need to be taken at equally spaced intervals, and no smoothing, interpolation, extrapolation, or other preprocessing of the data is necessary. The resulting input rate estimates are smooth and physiologically realistic, even with noisy data, and their accuracy is quantified. Derived quantities such as the proportion of the dose absorbed, and the mean and median absorption times, are also obtained, together with their error estimates. There are no arbitrarily valued parameters in the analysis, and no specific functional form, such as an exponential or polynomial, is assumed for the input rate functions.

Biological Availability↗

PubMed1991

The pharmacodynamics and pharmacokinetics of a novel thromboxane receptor blocking drug vapiprost (GR32191) after single intravenous doses in healthy subjects.

1 The effect of single, serially increasing, intravenous doses of a specific thromboxane receptor blocking drug, vapiprost, upon platelet aggregation induced ex vivo by the thromboxane A2 mimetic, U-46619, was examined in 12 healthy males. 2 Subjects received either 1 (n = 1 subject), 2 (n = 6), 3 (n = 2), or 4 (n = 3) administrations of vapiprost within the dose range 0.125 to 16 mg and, in random order, placebo on separate study days at intervals of at least 48 h. 3 All doses of vapiprost produced an immediate antagonism of U-46619-induced platelet aggregation in whole blood. Both the magnitude and duration of the rightward displacement of the concentration-effect curves increased with dose. Although lower doses produced parallel displacements of these curves, with the higher doses the maximum response to U-46619 was reduced such that 50% platelet aggregation was not achieved. After the 16 mg dose of vapiprost, virtually complete suppression of platelet aggregation (up to a concentration of 30 microM) was seen. This degree of inhibition was maintained for 2 h after dosing, following which there was a gradual return to pre-dose U-46619 sensitivity over the next 12 to 24 h. U-46619-induced platelet aggregation was unaffected by placebo. 4 Across the dose range, vapiprost was rapidly cleared from plasma, with an elimination half-life of 69-84 min and a plasma clearance of 514-721 ml min-1.(ABSTRACT TRUNCATED AT 250 WORDS)

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

PubMed1989

Single dose and steady-state pharmacokinetics of 4 mg and 8 mg oral salbutamol controlled-release in patients with bronchial asthma.

Fifteen patients with asthma were given salbutamol controlled-release (SCR) 4 mg or 8 mg twice daily for seven days, in a randomised double-blind cross-over design. Plasma salbutamol levels were measured after the first and fifteenth doses for a 12 h period following drug ingestion. At steady-state the geometric mean values for Cmax were 8.2 ng/ml for 4 mg, and 16.1 ng/ml for 8 mg. Median tmax values were 300 and 240 min respectively. The geometric mean AUC (0-12) were 4507 ng.min.ml-1 and 8980 ng.min/ml. Peak to trough fluctuation ratios were 0.577 and 0.572. There were no significant differences between 4 mg or 8 mg formulations, for any of the parameters measured, after appropriate corrections for dose. The concentration-time profiles at steady-state showed little fluctuation in plasma salbutamol levels over the twelve hour dosing interval. These results show that 4 mg and 8 mg formulations of SCR provide smooth plasma profiles at steady-state with a twice daily dosing regime.

Adult↗

PubMed1989

The estimation of moments: a technical note.

The calculation of several common pharmacokinetic parameters requires estimates of both the area under the curve of the concentration of the drug in a sampled fluid vs. time, and also the first moment about t = 0 of this area. It is proposed that the methods used to estimate these quantities should make consistent assumptions about the concentration of the drug. There appears to be an inconsistency in the standard published formulas in the case where concentration is interpolated linearly. A more consistent formula is derived.

Mathematics↗

PubMed1987

Maximum entropy and its application to the calculation of drug absorption rates.

A new method is presented for calculating the rate at which a drug enters the bloodstream after dosing, given the concentration of the drug in blood at various times. The method is based on the principle of maximum entropy, which has not been applied previously to pharmacokinetic problems. The resulting input rate functions are smooth and physiologically realistic, free of spurious oscillations yet still showing small-scale structure where there is evidence for it in the data. Blood samples do not need to be taken at equal intervals, and no preliminary smoothing or interpolation of the data is required.

Acetaminophen↗