The relation between plasma and tissue concentrations of antibiotics. Description of a method

A mathematical approach to calculate rate constants of the distribution of antibiotics between plasma and tissue is described. The calculations are based on the assumption that the drug moves between plasma and tissue passively according to the law of diffusion. Corrections can be made for binding to tissue and to plasma proteins. Two mathematical procedures are compared, one based on multiple regression analysis of areas under the curves of the plasma and tissue concentrations and the other on simultaneous curve-fitting to plasma and tissue concentration curves. The method is illustrated for amoxycillin and erythromycin in murine thigh muscle. The half-life of distribution to this tissue is less than 2 min for amoxycillin and about 10 min for erythromycin, and the ratio between the free extracellular tissue concentration and the total tissue content is 4.25 for the former and 0.35 for the latter.