title: Morning versus evening dosing of ibuprofen using conventional and time-controlled release formulations.
abstract: Many functions of the human body vary considerably during a day. These variations can lead to changes in drug plasma concentrations. In the study on healthy volunteers described here it was determined whether ibuprofen plasma levels following single oral doses of immediate-release and press-coated time-controlled release tablet formulations depend on time of drug administration (08:00 or 22:00 h). The difference between morning and evening dosing of the immediate-release formulation was minimal. The results with the press-coated formulation were unexpected having regard to results of previous studies on non-steroidal anti-inflammatory analgesics. Time to peak concentration was 6 h after morning administration, 4 h after evening administration. Both the rate and extent of bioavailability of ibuprofen were lower when dosing took place at 08:00 h than when dosing took place at 22:00 h. The influence of food on the pharmacokinetic profile of an evening dose of the press-coated formulation was also studied. When tablets were administered with a meal the ratio C(max)/AUC and t(max) and AUC values indicated that bioavailability was reduced. The main conclusion was that the chronopharmacokinetic behaviour of the press-coated ibuprofen tablet is related to the formulation, not the drug substance as such.
authors.affiliation: Department of Pharmacy, Division of Biopharmaceutics and Pharmacokinetics, P.O. Box 56, FIN-00014 University of, Helsinki, Finland.
authors.forename: M
authors.initials: M
authors.lastname: Halsas
authors.forename: J
authors.initials: J
authors.lastname: Hietala
authors.forename: P
authors.initials: P
authors.lastname: Veski
authors.forename: H
authors.initials: H
authors.lastname: Jürjenson
authors.forename: M
authors.initials: M
authors.lastname: Marvola
mesh_terms: D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D002214:Capsules; D002940:Circadian Rhythm; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D004334:Drug Administration Schedule; D004435:Eating / Q000502:physiology; D006801:Humans; D007052:Ibuprofen / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D013607:Tablets
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D002214:Capsules; D003692:Delayed-Action Preparations; D013607:Tablets; D007052:Ibuprofen