Pharmacology Review

Introduction

Ibuprofen, a nonsteroidal anti-inflammatory drug (NSAID), is a chiral compound derived from arylproprionic acid. It is used widely as an antipyretic, anti-inflammatory, and analgesic agent and for therapy of arthritis. It was approved by the United States Food and Drug Administration in 1974 and later became available as an over-the-counter drug. In 1979, Cocceani and associates (1) demonstrated a dose-dependent constriction of the ductus arteriosus caused by ibuprofen in newborn lambs. Its current use in human newborns was stimulated by its demonstrated improvement of cerebral blood flow (CBF) autoregulation in newborn animals (2) and its potential to offer some degree of neuroprotection. In contrast to indomethacin, ibuprofen did not decrease and impair regional blood flow to the brain in newborn infants and animals. (3)

In addition to neuroprotection, ibuprofen also may close the patent ductus arteriosus (PDA) in newborn humans, as has been shown in newborn lambs. A pilot study published in 1996 suggested that, compared with placebo, intravenous (IV) ibuprofen closed the PDA and shortened the hospital stay in preterm newborns with minimal renal adverse effects. (4) The development of two IV formulations of ibuprofen (ibuprofen lysine and ibuprofen THAM) permitted evaluation of this drug in preterm newborns. To date, efficacy, safety, dose finding, pharmacokinetic, and pharmacodynamic data in the newborn indicate that this drug is effective for ductal closure in preterm neonates. Data on safety depend on the formulation studied. (5)(6) This review examines the published data on ibuprofen up to June 2005 and concludes that ibuprofen lysine is a safe and effective drug for PDA closure in newborns.

Clinical Studies

More than 20 clinical trials have compared IV ibuprofen with placebo or indomethacin; others have evaluated the pharmacodynamic effects of the drug before and after its administration. Compared with placebo, IV ibuprofen decreased PDA, with little …