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. Clinical Pharmacology and Therapeutics (1980) 28, 289–295; doi: