Morning versus evening dosing of ibuprofen using conventional and time-controlled release formulations

Many functions of the human body vary considerably during a day. These vari ations can lead to changes in drug plasma concentrations. In the study on h ealthy volunteers described here it was determined whether ibuprofen plasma levels following single oral doses of immediate-release and press-coated t ime-controlled release tablet formulations depend on time of drug administr ation (08:00 or 22:00 h). The difference between morning and evening dosing of the immediate-release formulation was minimal. The results with the pre ss-coated formulation were unexpected having regard to results of previous studies on non-steroidal anti-inflammatory analgesics. Time to peak concent ration was 6 h after morning administration, 4 h after evening administrati on. Both the rate and extent of bioavailability of ibuprofen were lower whe n 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 w ith a meal the ratio C-max/AUC and t(max) and AUC values indicated that bio availability was reduced. The main conclusion was that the chronopharmacoki netic behaviour of the press-coated ibuprofen tablet is related to the form ulation, not the drug substance as such. (C) 1999 Elsevier Science B.V. All rights reserved.