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In certain slow release formulations the total dose of drug is subdivided into at least two fractions with different release capacities; these may display different degrees of bioavailability. In this type of formulation, calculation of the amount of biavailability by conventional methods does not permit one to differentiate the contribution of the different dose fractions to the total bioavailability of the formulation. This paper develops a model-independent method that permits optimization of the different components of bioavailability regarding amount and rate, combining convolution/deconvolution methods as well as non-linear regression. The method calculates bioavailability parameters by optimization of a prescribed input function in the form of a Laplace transform using the MULTI(FILT) program. The serum level curve after the administration of a slow release formulation is used as a response function obtained by convolution between a prescribed input function and a weighting function expressed as a polyexponential. The method was tested using simulated serum level data with added random error. In all cases the bioavailability parameters were calculated with good precision.

In the present study we propose a model-independent method based on the combination of the area under the curve of serum drug levels and the mean residence time for evaluating the amount of bioavailability when within-individual variability is present in the serum clearance of the drug, administered as a slow release formulation (SRF), and this follows linear pharmacokinetic behaviour. The method assumes that the modifications in the area under the curve of the serum levels induced by the within-individual variability in the kinetic behaviour of the drug lead to a variation of the same proportions in the mean residence time of the serum levels curve and that this parameter can be used as a correction factor in the ratio of the areas under the curve of serum levels in bioavailability studies. The method allows one to calculate the fraction of dose absorbed from the SRF without having to measure the disposition clearance of the drug either when using the reference formulation or when the drug is administered as a SRF. The method is easy to apply and has a minimum mathematical complexity. The validity of the method was evaluated using simulated data with either no error or containing a random error of 10%.

A new slow release formulation of the β-adrenoceptor antagonist, oxprenolol, and the diuretics triamterene and hydrochlorothiazide, were investigated alone and in combination in 2 groups of healthy volunteers. In the first study the new slow release oxprenolol alone gave lower ( P 0–24 values were comparable. In the second study, chronic administration of the new sustained release formulation in combination with triamterene and hydrochlorothiazide reduced ( P P