Cimetidine-associated patent ductus arteriosus is mediated via a cytochrome P450 mechanism independent of H2 receptor antagonism

► Preterm infants exposed to cimetidine have increased patent ductus arteriosus (PDA). ► Antacids that inhibit CYP enzymes relax the term and preterm mouse DA. ► CYP inhibition, but not H2 antagonism, alters DA tone in histamine deficient mice. ► Oxygen-induced DA constriction is selectively inhibited by cimetidine and famotidine.