Amiodarone/N-desethylamiodarone population pharmacokinetics in paediatric patients.

The population pharmacokinetics of amiodarone and its active metabolite, N-desethylamiodarone (DEA) were investigated in paediatric patients with arrhythmias, mainly supraventricular tachycardias. A total of 55 patients from the Department of Pediatric Intensive Care and Pediatric Cardiology at Necker-Enfants malades Hospital (Paris, France) provided 72 concentrations for both amiodarone and DEA following repeated oral or intravenous administration. Blood samples drawn for biological analyses were used for drug concentrations. Plasma amiodarone concentrations were measured by a liquid chromatography method coupled with mass spectrometry and the data were modelled using the software Monolix 2019R2. Parent pharmacokinetics was described with a 2-compartment open model and the metabolite formation was connected to the central parent compartment. Parameter estimates scaled allometrically on bodyweight (normalized to 70 kg) were, respectively (% relative standard errors, RSEs), 6.32 (31%) and 7.14 L/h (26%) for elimination (CL) and intercompartmental clearances and 167 (31%) and 3930 (32%) L for V1 and V2 . Oral bioavailability was 0.362 (21.5%). The clearance between subject variability (ω, square root of the variance) was 0.462 (RSE 21%). The proportional residual variabilities were respectively 0.453 (RSE 13%) and 0.423 (RSE 12%) for amiodarone and DEA respectively. The terminal half-lives were 34 and 14.5 days for amiodarone and DEA, respectively. A dosage schedule was established for 3 weight bands in 2 time periods. The high pharmacokinetic variability suggests that therapeutic drug monitoring might be useful to improve individual efficacy and safety.

Spontaneous Closure of the Arterial Duct after Transcatheter Closure Attempt in Preterm Infants.

(1) Background: Transcatheter closure of the patent arterial duct (TCPDA) in preterm infants is an emerging procedure. Patent arterial duct (PDA) spontaneous closure after failed TCPDA attempts is seen but reasons and outcomes are not reported; (2) Methods: We retrospectively included all premature infants <2 kg with abandoned TCPDA procedures from our institutional database between September 2017 and August 2021. Patients' data and outcomes were reviewed; (3) Results: The procedure was aborted in 14/130 patients referred for TCPDA. Two patients had spasmed PDA upon arrival in the catheterization laboratory and had no intervention. One patient had ductal spasm after guidewire cross. Four patients had unsuitable PDA size/shape for closure. In seven patients, device closure was not possible without causing obstruction on adjacent vessels. Among the 12 patients with attempted TCPDA, five had surgery on a median of 3 days after TCPDA and seven had a spontaneous PDA closure within a median of 3 days after the procedure. Only the shape of the PDA differed between the surgical ligation group (short and conical) and spontaneous closure group (F-type); (4) Conclusions: In the case of TCPDA failure, mechanically induced spontaneous closure may occur early after the procedure. Surgical ligation should be postponed when clinically tolerated.