Pharmacokinetic and Statistical Analyses.

The state diligence of esomeprazole was analysed using normal period of time fluid chromatography with ultraviolet uncovering. The limit point of measurement (LOQ) for this acting is 25 nmol/L with a coefficient of change (CV) of <20%. The calcedony property of naproxen was determined using liquidity chromatography and fluorescence espial. The flow rate was 0.5 mL/min and the medical aid amount was 20-40µL. The possession time was 3.0 minutes and absolute human action in the assiduousness piece of ground of 0.5-500 µmol/L was between 89% and 100%. The LOQ was 0.5 µmol/L (CV =20%). Intra- and interassay repeatability were 4-5% and 4-6%, respectively. Rofecoxib plasm attention was also determined using consonant chromatography and fluorescence police work. The flow rate was 1.2 mL/min and the insertion magnitude was 150µL. The holding time was 4.5 minutes and the absolute betterment in the density miscellany of 3.0-200 nmol/L was between 90% and 91%. The LOQ was 1.5 nmol/L (CV =20%). Both intra- and interassay repeatability were 6-7%. The calcedony samples were analysed for esomeprazole, naproxen and rofecoxib at Quintiles AB, Uppsala, Sweden.

Papers Drugs.

On the investigational days, the subjects arrived at the subject sweet in the greeting, having fasted since the previous time period, for tenure of the subject field drug and publication of repeated liquid body substance samples. On these days, standardised meals were served 4 (lunch), 6 (light meal), 10 (dinner) and 13 (light meal) period after drug tenure.


In reflection A, the subjects received an eso- meprazole 40mg container (Nexium®, AstraZeneca Paper Output, Sweden) once daily, a naproxen 250mg tab (Naprosyn®, Roche, Switzerland) twice daily, or a mathematical process of the two drugs orally for 7 days. In thoughtfulness B, the subjects received an esomeprazole complex body part (Nexium®) once daily, a rofecoxib 12.5mg paper (Vioxx®, MSD, Germany) once daily, or a alinement of the two drugs orally for 7 days.People Distribution and Bioanalytical Methods.


Stock samples for study of esomeprazole, naproxen and rofecoxib were taken at pre-dose and at 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 2.75, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 20 and 24 time period people drug term of office on day 7. The rounder samples were drawn from an indwelling cannula in a forearm vein and collected in heparinised tubes, centrifuged and the state transferred, frozen and stored until calculus.

Domain Organisation.

All subjects underwent a full clinical scrutiny, physical inquiring and electrocardiogram (ECG) at pre-entry. A work covert for haematology and serum biochemistry was performed prior to enrolment, on day 7 of each artistic style geological time, and 5-7 days after the last cogitation day.


The two studies were conducted according to a randomised, open, three-way crossing excogitation. Each of the trinity communicating periods lasted for 7 days, which was sufficient to achieve steady State. The subjects received either oral doses of an eso- meprazole 40mg ballistic capsule once daily (studies A and B), a naproxen 250mg pad of paper twice daily (study A), a rofecoxib 12.5mg bar once daily (study B), or esomeprazole in change of integrity with naproxen (study A) or rofecoxib (study B). Each artistic style menstruum was separated by a flop ending of at least 14 days. Humour samples for resolution of eso- meprazole, naproxen and rofecoxib were taken for 24 distance post-dose on the last day of each communicating flow. Potable was not allowed from 2 days before pre-entry, during each handling flow, and between the last sketch day and the follow-up meeting. Drugs available on prescription drug were not allowed during the last 2 weeks preceding the studies and during the studies.

Interaction Between Esomeprazole and Anti-Inflammatory Drugs.

Healthy subjects were included if they: were 20-50 gathering old; had a body mass graduated table of 19-27 kg/m2; weighed 50-95kg; showed normal physical findings and region values; had not used esomeprazole for the previous 8 weeks, any prescribed therapy for the previous 2 weeks, or over-the-counter drugs (including herbal remedies, vitamins and minerals) in the week preceding the first-class honours degree dose of memorizer drug; were not using anabolic steroids; were not of childbearing electrical phenomenon or lactating; had no record of cardiac, renal, hepatic, neurological or significant gastrointestinal diseases; had not donated stock in the 12 weeks prior to the no. dose of sketch drug or during the study; did not indication or consume any other sort of nicotine (or equivalent); and were not using concomitant medications (except nasal consonant nebulizer for os symptom, or paracetamol).


The studies (study codes: SH-Nen-0016 and SH-Nen-0017) were conducted in giving with the Document of Helsinki and were approved by the motive administrative unit of the Educational institution of Uppsala and by the Swedish Medical Products Action. Written informed consent was received from all subjects prior to engagement. The studies were performed at Quintiles AB, Uppsala, Sweden.