Reference : Estimation of the comparative therapeutic superiority of QD and BID dosing regimens, bas...
Scientific journals : Article
Physical, chemical, mathematical & earth Sciences : Multidisciplinary, general & others
Human health sciences : Pharmacy, pharmacology & toxicology
Estimation of the comparative therapeutic superiority of QD and BID dosing regimens, based on integrated analysis of dosing history data and pharmacokinetics
Comté, Laetitia [Université de Liège - ULg > Département de mathématique > Statistique (aspects expérimentaux) >]
Vrijens, Bernard mailto [Université de Liège - ULg > > Département de mathématique > > >]
Tousset, Eric mailto [Pharmionic Research Center > > > >]
Gérard, Paul mailto [Université de Liège - ULg > Département de mathématique > Statistique (aspects expérimentaux) >]
Urquhart, John [University of California, San Francisco Medical Center > Department of Biopharmaceutical Sciences > Center for Drug Development Science > >]
Journal of Pharmacokinetics and Pharmacodynamics
Springer/Plenum Publishers
Yes (verified by ORBi)
New York
[en] adherence ; compliance-HIV ; time history of drug intake ; PI concentration in plasma ; drug dosing regimens ; once-daily dosing ; twice-daily dosing ; pharmacokinetics ; pharmacodynamics ; systems therapeutics
[en] Once-daily dosing almost invariably shows a slightly higher percentage of prescribed doses taken than does twice-daily dosing. Many pharmaceutical scientists, regulators, and prescribers have considered this finding to signify the therapeutic superiority of once-daily dosing. The therapeutically more relevant question, however, is not the percentage of prescribed doses taken but the comparative impact of missed doses on the pharmacologic effects of a drug under the two dosing regimens. A key point in this regard is that the pharmacokinetic equivalent of a single missed once-daily dose is 2-3 sequentially omitted twice-daily doses. Thus, an important parameter in comparing the two regimens is the probability of two or three twice-daily doses being sequentially omitted, versus the probability of missing a single once-daily dose. Our data indicate that the probability of sequential omission of 2-3 twice daily doses is half the probability of omission of a single once-daily dose. For that reason, a twice-daily regimen could prove to be superior to a once-daily regimen in maintaining drug concentrations within a therapeutically desirable range. A more important consideration, however, is to maintain not just the concentration of drug in plasma, but the drug's therapeutic action. The duration of therapeutic drug action following a last-taken dose is not only drug-specific, but also, for some drug, dependent on the pharmacodynamic properties. Judging the comparative superiority of one dosing regimen over another requires knowledge of the drug's duration action after a last-taken dose, plus knowledge of the comparative probabilities of the various patterns of dose omission. When applied to HIV protease inhibitors, a twice-daily regimen appears to be better than an once-daily regimen in maintaining therapeutically effective drug actions.
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