title: Time of effect duration and administration interval for sitagliptin in patients with kidney failure.
abstract: A measure correlating the time course of the effect with the time course of concentrations could be helpful in drug dosing. We propose a new equation with explicit solutions for calculating the effect duration. A specific effect fraction is selected (fr) and the time of fractional effect duration (TED.fr) can be derived as a function of the elimination half-life by combining linear elimination kinetics with sigmoid effect dynamics. This new measure is applied to the example of sitagliptin, whose elimination half-life increases from 10.1 to 28.4 h in patients with kidney failure. Under normal multiple-dose conditions, the 24-h sitagliptin administration interval corresponds to a 0.90 time of fractional effect duration (TED.90). A dose reduction to one-fourth or 25 mg every 24 h is proposed for patients with kidney failure; this results in a TED.90 of 45 h, i.e. 21 h longer than the proposed 24-h administration interval (+88 %). The proportional dosing alternative of 100 mg every 96 h would result in a TED.90 of 64 h, which is 32 h less than the 96-h administration interval (-33 %). With a half dose of 50 mg and a doubled administration interval of 48 h, the TED.90 is 51 h in kidney failure, only 3 h longer than the latter administration interval (+6 %). We conclude that our general equation can be applied to rapidly calculate the specific time of effect duration for the different dose schedules.
authors.affiliation: Division of Nephrology, Department of Internal Medicine 1, University Hospital, Albert Einstein Allee 23, 89070, Ulm, Germany, frieder.keller@uni-ulm.de.
authors.forename: Frieder
authors.initials: F
authors.lastname: Keller
authors.forename: Bertram
authors.initials: B
authors.lastname: Hartmann
authors.forename: David
authors.initials: D
authors.lastname: Czock
mesh_terms: D006207:Half-Life; D006801:Humans; D011719:Pyrazines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D051437:Renal Insufficiency / Q000378:metabolism*; D000068900:Sitagliptin Phosphate; D013997:Time Factors; D014230:Triazoles / Q000008:administration & dosage / Q000493:pharmacokinetics*
chemical_list: D011719:Pyrazines; D014230:Triazoles; D000068900:Sitagliptin Phosphate