Oral and Intravenous Pharmacokinetics of Milrinone in Human Volunteers

Population pharmacokinetics and dosing regimen design of milrinone in preterm infants

“…8 The pharmacokinetic changes of decreased clearance, pro-longed half life and larger volume of distribution observed in our study are consistent with the physiological differences noted in preterm infants and can be explained by immature renal function and higher total body water compartment seen in preterm infants. 17 18 26 Taken together these findings have implications for dose selection and the pitfalls of scaling doses in mg/kg from infants and children for preterm infants.…”

“…Early studies in healthy subjects confirmed that milrinone is predominately eliminated by renal excretion with a fraction excreted unchanged of approximately 80%. 8 The renal clearance of milrinone was calculated to be approximately 10 times higher than the expected renal clearance by filtration of unbound drug clearly indicating that renal secretion is a major contributor to milrinone renal excretion. The exact renal secretion pathway has not been investigated.…”

“…It acts by decreasing systemic vascular resistance, increasing cardiac contractility and cardiac output. 8 Studies show that milrinone significantly improves cardiac function in children and neonates following cardiac surgery [9][10][11][12] and in children with septic shock. 13 14 However, milrinone has not been evaluated in the very preterm infant with low cardiac output.…”

Milrinone Reduces Cerebral Vasospasm After Subarachnoid Hemorrhage of WFNS Grade IV or V

“…The hemodynamic effects of inhibiting phosphodiesterase include enhanced cardiac contractility, reduced afterload, and improved diastolic compliance. 19) The optimal serum concentration of milrinone (100-200 ng/ml) will cause increases in both cardiac index and stroke work index, as well as a decrease in pulmonary capillary wedge pressure without any significant change in heart rate or blood pressure. 1,3) These properties of milrinone are appropriate for the treatment of cerebral vasospasm but intravenous infusion of milrinone is not sufficiently preventive.…”

Retrospective Evaluation of Milrinone Pharmacokinetics in Children With Kidney Injury

“…In patients with acute kidney injury (AKI) on standard dosing, accumulation of milrinone concentration has been documented. 12 Because of its high protein binding, milrinone is not cleared effectively by continuous renal replacement therapy (CRRT). 7,11 Therapeutic drug monitoring (TDM) is not routinely used for milrinone dose adjustment in the clinical setting.…”