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Biomedical subjects

D P Vaughan

Publications and source records attributed to D P Vaughan.

At least 19 recordsLinked to original sources
PubMed1989

On the transformation of compartmental systems and the indeterminacy of the volume of distribution.

A general compartmental system with multiple-point elimination is transformable to a single-point elimination system. Transformation is achieved by a similarity transformation of the rate constant matrix, A, with a diagonal matrix, D. The elements of D (1, d1, d2,...) are equivalent to the "first-pass" effect between compartments and compartment 1. Application of the derived transformation demonstrates that the volume of distribution as defined by the normalized first-moment function is a minimal volume of distribution when there is no "first-pass" effect between the drug input compartment and the observation compartment. In all other cases, the volume of distribution is a meaningless metric since it may be a minimal or maximal metric and the exact status is indeterminate. Theorems on the non-negativity of the elements of (-A)-1 are derived.

Chemistry, Pharmaceutical↗
PubMed1984

Theorem on the apparent volume of distribution and the amount of drug in the body at steady state.

For an N-compartmental system, with irreversible drug loss from the sampled compartment, the equilibrium concentration, C (infinity), obtained with a zero-order drug input is related to the total amount of drug in the system, T, by C (infinity) V = T. The scalar V is the volume of distribution of the corresponding closed system. The moment functions of the open system define V, and hence T is directly calculable. The derivation is general in the sense that the topology of the system is not specified and no functional form for C (t) is required.

Humans↗
PubMed1980

Mathematical basis and generalization of the Loo-Riegelman method for the determination of in vivo drug absorption.

A general numerical deconvolution method is derived for the determination of in vivo drug input functions. The derivation is based on linear interpolation of observed drug concentrations and deconvolution of the resulting trapezoidal function. Derived in vivo input functions are discontinuous. A general expression for the cumulative drug input is also derived. The latter expression is a generalization of the Loo-Riegelman equations. This deconvolution method give similar results to the "point-area" deconvolution method when deriving in vivo drug input functions.

Intestinal Absorption↗
PubMed1979

Number of exponential terms describing the solution of an N-compartmental mammillary model: vanishing exponentials.

The solution for a linear mammillary model is always described by a summation of m + 1 negative exponential terms with constant coefficients. m + 1 less than or equal to N, where N is the number of compartments in the model. m is equal to the number of distinct values for the peripheral Ej values. Use is made of matrix notation and the theorems of Browne concerning the eigenvalues of a matrix. The consequences of vanishing exponentials are derived, and in particular the apparent volume of distribution frequently calculated from experimental data is shown not to be unique.

Animals↗
PubMed1976

Simple transformation method for predicting plasma drug profiles from dissolution rates.

A transformation factor is described which related in vitro drug dissolution from a preparation to the corresponding in vivo plasma drug concentrations. This factor, derived from the dissolution profile and the corresponding in vivo plasma concentration of a single formulation, was used to predict plasma concentration profiles of similar formulations simply from dissolution data.

Methods↗
PubMed1976

General derivation of the ideal intravenous drug input required to achieve and maintain a constant plasma drug concentration. Theoretical application to lignocaine therapy.

A constant plasma drug concentration can be achieved and maintained by the intravenous administration of an initial bolus loading dose in conjunction with a constant rate and an exponential intravenous drug infusion. The drug input required to achieve a constant plasma drug concentration is derived without making any assumptions about the nature of drug distribution within the body or elimination from the body.

Infusions, Parenteral↗
PubMed1976

The influence of smoking on the intersubject variation in pentazocine elimination.

The cumulative urinary excretion over 24 h of pentazocine, under conditions of acidic urinary pH, has been measured in smokers and non-smokers using both male and female subjects (seventy subjects in total). A restricted urban population was studied. An overall three-fold inter-subject variation in elimination was observed. The cumulative urinary excretion of pentazocine was normally distributed in both smokers and non-smokers. Smokers metabolize 40% more pentazocine than non-smokers. It is concluded that induction is principally responsible for the observed subject variability.

Adult↗
PubMed1975

General theory for rapidly establishing steady state drug concentrations using two consecutive constant rate intravenous infusions.

Steady state plasma drug concentrations can be achieved rapidly and safely by a drug input mode consisting of two consecutive constant rate intravenous infusions. A general method for calculating the relative rates of the two infusions is presented. The derivation is independent of the concepts of compartmental distribution and elimination of drugs within the body.

Infusions, Parenteral↗
PubMed1975

General pharmacokinetic equations for linear mammillary models with drug absorption into peripheral compartments.

General equations are derived for the disposition functions of any compartment in a linear mammillary model, when the system input occurs into a peripheral compartment. Laplace transforms and matrix algebra are used to derive these equations. Equations describing the time-course of a drug in any compartment are readily obtainable using disposition and input functions.

Intestinal Absorption↗