Propranolol Plasma Monitoring in Children Submitted to Surgery of Tetralogy of Fallot by a Micromethod Using High Performance Liquid Chromatography

Abstract

Sanches C, Galas FRBG, Silva AGO de M, Carmona MJC, Auler Jr. JO, Santos SRCJ. Propranolol plasma monitoring in children submitted to surgery of tetralogy of Fallot by a micromethod using high performance liquid chromatography. Clinics. 2007;62(3):215-24. OBJECTIVE:To evaluate the analytical micromethod using liquid chromatography for the quantification of propranolol in children submitted to surgery of tetralogy of Fallot (TLF). Methods: Only 0.2 mL of plasma is required for the assay. Peaks eluted at 8.4 (Propranolol) and 17.5 min (verapamil, internal standard) from a C18 column, with a mobile phase 0.1 M acetate buffer, pH 5.0, and acetonitrile (60:40, v/v) at flow rate 0.7 mL/min, detected at 290 nm (excitation) and 358 nm (emission). Surgery was started 776 min of drug administration (8.7mg, mean); seven blood samples were collected from six patients (4M/2F; 2.1yrs;11.5kg; 0.80m; 18.9kg/m 2 ). RESULTS: Confidence limits of the method showed high selectivity and recovery, sensitivity of 0.02ng/mL, good linearity (0.05-1000ng/mL), precision of 8.6% and accuracy of 3.1%. The mean duration of surgery was 283.2min, with the patients remaining under cardiopulmonary bypass (CPB) for 114min. A declining curve of propranolol plasma concentration was obtained after the last dose in the night that preceded the day of surgery. Plasma concentration also was normalized with hematocrit due to the hemodilution caused by the CPB procedure. On the other hand a decrease on drug plasma concentration was obtained between periods, the beginning of surgery to the postoperative day 2 (7.09 ng/mL and 0.05 ng/mL, p<0.05 respectively) and from the end of CPB to the postoperative day 2 (2.79ng/mL e 0.05ng/mL, p<0.05). CONCLUSION: Propranolol monitoring of plasma concentrations of children (TLF) normalized after the last preoperative dose revealed a decline from the beginning of surgery to the second postoperative day, suggesting that, once redistribution was restored, propranolol washout was complete.

Population Pharmacokinetics and Pharmacodynamics of Oral Propranolol in Pediatric Patients With Infantile Hemangioma

“…[5][6][7][8] However, in children, especially infants, such information is limited. 9,10 In a previous study, body weight-normalized oral clearance was similar in infants as in adults. 11 In this retrospective post hoc analysis we developed a population pharmacokinetic model to describe propranolol pharmacokinetics in infantile hemangioma patients and identified potential sources of pharmacokinetics variability.…”

“…In adults, the pharmacokinetic properties of propranolol hydrochloride are well known . However, in children, especially infants, such information is limited . In a previous study, body weight–normalized oral clearance was similar in infants as in adults…”

At what age should tetralogy of Fallot be corrected?

“…Studies have shown that patients on long-term propranolol at the time of corrective surgery are not at a disadvantage, 24 , 25 although Barazzone et al 26 demonstrated that the effects of isoproterenol were blunted but could be overcome by giving higher doses of the adrenergic agent. To avoid intra-operative problems, Garson et al 22 discontinued propranolol 4 days before surgery, but this risks having hypercyanotic spells before or even during surgery.…”

Propranolol pharmacokinetics in infants treated for Infantile Hemangiomas requiring systemic therapy: Modeling and dosing regimen recommendations

“…In infants, limited information was available on the pharmacokinetic profile and plasma exposure of propranolol after oral administration. Until 2013, only 92 plasma concentrations observed after oral administration of propranolol in children from 8 weeks‐ to 13 years‐old were documented in 3 publications: mean concentrations ranged between 0.05 and 57 ng mL −1 for different doses and regimen . In 2013, published results in 4 term and 23 preterm neonates treated with oral propranolol at 0.25 or 0.5 mg kg −1 every 6 hour in which 1000 concentrations were measured by serial dried blood spots.…”

“…Until 2013, only 92 plasma concentrations observed after oral administration of propranolol in children from 8 weeks-to 13 years-old were documented in 3 publications: mean concentrations ranged between 0.05 and 57 ng mL À1 for different doses and regimen. 32,34,40 In 2013, 14 published results in 4 term and 23 preterm neonates treated with oral propranolol at 0.25 or 0.5 mg kg À1 every 6 hour in which 1000 concentrations were measured by serial dried blood spots. After 0.5 mg/kg/6 hour, the mean maximum concentrations were 71.7 AE 29.8 ng mL À1 .…”