Design of infusion regimens to achieve and maintain a predetermined plasma drug level range

A method is proposed for the design of dosage regimens using two consecutive constant-rate intravenous infusions to rapidly achieve and maintain plasma drug levels within a predetermined range. By this method, the plasma level will rise to a predetermined maximum at the end of the loading infusion, decrease rapidly to a chosen fraction of the ultimate steady-state level, and then slowly rise to the steady-state level. The method may be particularly useful for drugs exhibiting extensive "multi-compartment" kinetics. Compared with other methods, this approach allows either or both a shorter loading infusion and a lower peak plasma level. Application of this method to clomethiazole therapy for the sedation of pregnant women at term is also discussed.