Pharmacokinetics of intravenous ibuprofen: Implications of time of infusion in the treatment of pain and fever

摘要

Intravenous NSAIDs are playing an increasingly large role in analgesia, anti-inflammation and antipyresis in the hospitalized setting. For many years, ketorolac was the only intravenous NSAID available in the US, but in 2009 intravenous ibuprofen was approved by the US FDA for the treatment of pain and fever in adults. In developing intravenous ibuprofen, a range of times of infusion and dosing levels have been utilized and compared with the oral route of administration. The earliest studies utilized a 60-minute infusion, and later a 30-minute infusion was used for the pivotalregistration studies demonstrating efficacy and safety. Another recent trial in healthy volunteers demonstrated a safe and tolerable rapid infusion (57 minute) of intravenous ibuprofen. The pharmacokinetic data from all of the clinical trials on 400 and 800mg doses of intravenous ibuprofen were compiled, and pharmacokinetic modelling was utilized to simulate any data not acquired in the clinical studies. The pharmacokinetic profile of the following doses was modelled: 30-minute infusion of 800mg intravenous ibuprofen, 5- to 7-minute infusion of 400mg intravenous ibuprofen and 400mg ibuprofen oral tablet. These pharmacokinetic analyses revealed that, in general, maximum plasma concentration (Cmax) decreases considerably as the length of the infusion increases and that an oral dose is not able to achieve the Cmax level of any intravenous dose. For the rapid infusion, Cmax was twice that of the oral dose and, as expected, time to Cmax (tmax) was much more rapid than with the oral dose. However, the oral dose still maintained virtually 100 oral bioavailability. The efficacy of intravenous ibuprofen in terms of pain and fever has also been studied and this review found the drug to be efficacious for both indications. Future areas of study should include assessment of the analgesic and antipyretic efficacy of a rapid (5- to 10-minute) infusion and further assessment of pre-emptive administration of intravenous ibuprofen as part of a multimodal analgesic approach in the surgical setting.