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.
D000927:Anticonvulsants / Q000008:administration & dosage / Q000097:blood; D002719:Chlormethiazole / Q000008:administration & dosage / Q000097:blood; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007263:Infusions, Parenteral / Q000379:methods*; D007700:Kinetics; D008954:Models, Biological; D004364:Pharmaceutical Preparations / Q000097:blood*; D011247:Pregnancy
D000927:Anticonvulsants; D004364:Pharmaceutical Preparations; D002719:Chlormethiazole