Dopamine plasma clearance is increased in piglets compared to neonates during continuous dopamine infusion

TY - JOUR

T1 - Dopamine plasma clearance is increased in piglets compared to neonates during continuous dopamine infusion

AU - Rasmussen, Martin B.

AU - Gramsbergen, Jan Bert

AU - Eriksen, Vibeke R.

AU - Greisen, Gorm

PY - 2018/2/1

Y1 - 2018/2/1

N2 - Aim: Piglets models have often been used to study the effects of dopamine infusion on hypotension in neonates. However, piglets need higher doses of dopamine than neonates to increase blood pressure. We investigated whether this difference was due to interspecific difference in dopamine pharmacokinetics. Methods: Arterial blood samples were drawn from six neonates admitted to the neonatal intensive care unit of Copenhagen University Hospital and 20 newborn piglets during continuous dopamine infusion. Furthermore, to estimate the piglet plasma dopamine half-life, blood samples were drawn at 2.5-minute intervals after the dopamine infusion was discontinued. The plasma dopamine content was analysed by high-performance liquid chromatography with electrochemical detection. Results: The dopamine displayed first-order kinetics in piglets and had a half-life of 2.5 minutes, while the median plasma clearance was 627.9 mL/kg/minute (interquartile range 452.6–1914.4). Both piglets and neonates showed large interindividual variations in plasma clearance, but the median tended to be lower in neonates (384.9, interquartile range 114.2–480.2 mL/kg/minute). Conclusion: Our results suggest that pharmacokinetic differences may explain the interspecific difference in required doses of dopamine infusion to increase blood pressure. This is important when translating the results obtained in piglet models to treating neonatal hypotension with dopamine.

AB - Aim: Piglets models have often been used to study the effects of dopamine infusion on hypotension in neonates. However, piglets need higher doses of dopamine than neonates to increase blood pressure. We investigated whether this difference was due to interspecific difference in dopamine pharmacokinetics. Methods: Arterial blood samples were drawn from six neonates admitted to the neonatal intensive care unit of Copenhagen University Hospital and 20 newborn piglets during continuous dopamine infusion. Furthermore, to estimate the piglet plasma dopamine half-life, blood samples were drawn at 2.5-minute intervals after the dopamine infusion was discontinued. The plasma dopamine content was analysed by high-performance liquid chromatography with electrochemical detection. Results: The dopamine displayed first-order kinetics in piglets and had a half-life of 2.5 minutes, while the median plasma clearance was 627.9 mL/kg/minute (interquartile range 452.6–1914.4). Both piglets and neonates showed large interindividual variations in plasma clearance, but the median tended to be lower in neonates (384.9, interquartile range 114.2–480.2 mL/kg/minute). Conclusion: Our results suggest that pharmacokinetic differences may explain the interspecific difference in required doses of dopamine infusion to increase blood pressure. This is important when translating the results obtained in piglet models to treating neonatal hypotension with dopamine.

KW - Dopamine

KW - Hypotension

KW - Neonates

KW - Newborn piglets

KW - Pharmacokinetics

UR - http://www.scopus.com/inward/record.url?scp=85028722918&partnerID=8YFLogxK

U2 - 10.1111/apa.14018

DO - 10.1111/apa.14018

M3 - Journal article

C2 - 28796889

AN - SCOPUS:85028722918

SN - 0803-5253

VL - 107

SP - 249

EP - 254

JO - Acta Paediatrica, International Journal of Paediatrics

JF - Acta Paediatrica, International Journal of Paediatrics

IS - 2

ER -