The purpose of this study is to determine oral paracetamol and ibuprofen efficacy and safety in relation to serum levels in closure of patent ductus arteriosus in preterm infants.

To determine oral paracetamol and ibuprofen efficacy and safety in relation to serum levels in closure of patent ductus arteriosus in preterm infants.

Eighty preterm infants with patent ductus arteriosus will be enrolled in this prospective-randomized study. Patients will receive oral ibuprofen at an initial dose of 10 mg/kg, followed by 5 mg/kg at 24 and 48 h or oral paracetamol 15 mg/kg per dose every 6 hours for 3 days.

One of the following echocardiographic criteria of a duct size > 1.5 mm, a left atrium-to-aorta ratio > 1.5, left-to-right shunting of blood, end diastolic reversal of blood flow in the aorta, or poor cardiac function in addition signs of patent ductus arteriosis determined the need of treatment.

Three consecutive blood sample from infants for 3 days before dose application of drugs(ibuprofen and paracetamol will be obtained.

The relation of pharmacokinetics of drugs to drug response will be evaluated

Inclusion Criteria:

• Birth weight below 1250 gram
• Diagnosed patent ductus arteriosus by Echocardiographic examination

Exclusion Criteria:

• Accompanied other congenital cardiac anomalies
• Severe thrombocytopenia < 60.000
• Severe intracranial bleeding (Grade III - IV)
• Intestinal abnormality and necrotising enterocolitis