Transfer of propafenone and 5‐OH‐propafenone to foetal plasma and maternal milk [letter]

Libardoni, M; Piovan, Donatella; Busato, Eduarda Maciel; Padrini, Roberto

doi:10.1111/j.1365-2125.1991.tb03945.x

Cited by 20 publications

(4 citation statements)

References 6 publications

(4 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The M/P obs for propafenone was lowest among the three in this study. There is one report for propafenone [9] and the value is Table 1 Pharmacokinetic profiles of three antiarrhythmic drugs comparable to that reported in this study. The equation of Begg gave a close M/P pred for pilsicainide.…”

supporting

confidence: 85%

Pilsicainide in breast milk from a mother: comparison with disopyramide and propafenone

Wakaumi

Tsuruoka

Sakamoto

et al. 2004

Brit J Clinical Pharma

View full text Add to dashboard Cite

Information about the transfer of antiarrhythmic drugs into milk is available. However, results for the same drug sometimes vary. This variation may be due to factors such as interpatient variation of drug transfer or the small number of patients in the studies. Equations are useful for predicting drug transfer into milk [1]. Pilsicainide is a new class I antiarrhythmic drug used in Japan. We collected serial specimens of plasma and milk after a single dose of three different antiarrhythmic drugs, including pilsicainide, in a healthy mother. We also compared the results with an equation for predicting the milk/plasma ratio.One healthy nursing mother (one of the authors, M.W.; body weight 56 kg) took a single oral dose of either pilsicainide (50 mg), disopyramide (100 mg) or propafenone (150 mg) after a 12-h fast. The wash-out period between each dose was 4 weeks and the order of the section was randomly chosen. She was prohibited from breast feeding on trial days. Blood and milk samples were collected at 1, 2, 3, 4, 6, and 12 h after each dosing. Breast milk samples were collected by manual expression and milk pH was measured anaerobically. For sampling milk, breasts were emptied of milk at each time point and a stirred aliquot was taken for analysis. Protein binding of each drug was measured after microultrafiltration. Concentrations of pilsicainide, propafenone, 5-(OH)propafenone and disopyramide were measured using high-performance liquid chromatography [2,3] or enzyme immunoassay [4]. The detection limit was 0.06 m g ml -1 , 10 ng ml -1 , 10 ng ml -1 , and 0.07 m g ml -1 , for pilsicainide, propafenone, 5-(OH)propafenone and disopyramide, respectively. The milk/ plasma ratio of each drug (M/P obs ) was calculated by the ratio of AUC 0 -12 h for milk and plasma, obtained by the trapezoidal method. Pharmacokinetic parameters of pilsicainide after a single oral administration were estimated using the least square method applied to a one-compartment open model with first-order absorption and elimination. The maximum and minimum serum concentrations of pilsicainide at steady state were calculated by the estimated pharmacokinetic parameters using computer software. The body weight-adjusted relative infant dose of the drug was calculated from the assumption that a baby takes 150 ml kg -1 day -1 of milk. Finally, we estimated the M/P ratio (M/P pred ) according to the previously reported equations of Begg [1], and compared the results with actual M/P obs . The Ethics Committee of the Medical School approved the protocol.The pilsicainide concentration in milk was higher than that in plasma at each observation point, whereas disopyramide and propafenone concentrations in milk were lower than those in plasma (Table 1). Estimated C max / C min at steady state, M/P obs , protein binding, milk pH, octanol/water partition coefficient at pH 7.2 and pKa used for the prediction are also shown.The value of M/P for disopyramide varies widely (from 0.4 to 0.9) among reports [5][6][7]. Because the protein binding ratio of disopyr...

show abstract

supporting

confidence: 85%

Pilsicainide in breast milk from a mother: comparison with disopyramide and propafenone

Wakaumi

Tsuruoka

Sakamoto

et al. 2004

Brit J Clinical Pharma

View full text Add to dashboard Cite

show abstract

“…Because of its safer profile, we chose propafenone as second-line therapy, as also recommended by others (Gembruch et al 1988). Propafenone is usually well tolerated, has good transplacental passage (Libardoni et al 1991;Blomström-Lundqvist et al 2003) and is effective in the prophylaxis of supraventricular arrhythmias. In a randomized clinical trial, propafenone reduced the recurrence rate of arrhythmias by one fifth compared with placebo (Pritchett et al 1991).…”

Section: Discussionmentioning

confidence: 98%

Fetal arrhythmias: Natural history and management

Vergani

Mariani

Ciriello

et al. 2005

Ultrasound in Medicine & Biology

View full text Add to dashboard Cite

“…[24] In the second and third trimesters, propafenone has been used to treat maternal arrhythmias with no observable effect on the heart rates of the fetuses. [36,37] The US FDA has designated propafenone as a pregnancy category C drug. However, studies on experimental animals are insufficient to demonstrate proof of teratogenicity while research on human pregnancy also remains scarce.…”

Section: Discussionmentioning

confidence: 99%

Effect of Rythmol (propafenone HCl) administration during pregnancy in Wistar rats

Abd-Allah

Amin

Ghareeb

et al. 2022

J Biochem & Molecular Tox

View full text Add to dashboard Cite

Propafenone is a well‐known Class 1C antiarrhythmic agent that has sodium channel blocking properties as well as the ability to block 13 other channels and a modest calcium antagonistic effect. Propafenone has a profound electrophysiologic effect on auxiliary atrioventricular circuits and in patients with atrioventricular nodal reentry tachycardia can obstruct conduction in the fast conducting pathway. Furthermore, propafenone is less likely than other Class 1C drugs to cause proarrhythmia. However, although this medicine can pass through the placenta, the effects during pregnancy remain unknown. Here, we investigated the potential teratogenic and genotoxic effects of Rythmol during rat development. Pregnant Wistar rats received 46.25 mg/kg body weight of propafenone daily by gavage from Gestation Day (GD) 5 to GD 19. At GD 20, the dams were dissected, and their fetuses were assessed via morphologic, skeletal, and histologic investigation. In addition, a comet assay was used to measure DNA impairment of fetal skull osteocytes and hepatic cells. The study showed that propafenone treatment of pregnant rats led to a marked decrease in gravid uterine weight, number of implants/litter, number of viable fetuses, and bodyweight of fetuses but a clear increase in placental weight and placental index in the treated group. Frequent morphologic abnormalities and severe ossification deficiency in the cranium bones were observed in the treatment group. Various histopathological changes were observed in the liver, kidney, and brain tissues of maternally treated fetuses. Similarly, propafenone induced DNA damage to examined samples. Thus, our study indicates that propafenone may be embryotoxic in humans.

show abstract

Transfer of propafenone and 5‐OH‐propafenone to foetal plasma and maternal milk [letter]

Cited by 20 publications

References 6 publications

Pilsicainide in breast milk from a mother: comparison with disopyramide and propafenone

Pilsicainide in breast milk from a mother: comparison with disopyramide and propafenone

Fetal arrhythmias: Natural history and management

Effect of Rythmol (propafenone HCl) administration during pregnancy in Wistar rats

Contact Info

Product

Resources

About