Pharmacokinetics of oral bromocriptine in postpartum patients

Cardiomyopathy is a leading cause of maternal morbidity and mortality. A prolactin fragment has been implicated in the pathogenesis, and preliminary data suggest that bromocriptine-a dopamine receptor agonist that inhibits prolactin secretion-is a promising adjunctive therapy. However, bromocriptine pharmacokinetic (PK) data are largely derived from healthy males. Our objective was to conduct a postpartum oral bromocriptine PK study to inform a future trial to test the potential benefit of bromocriptine for add-on peripartum cardiomyopathy (PPCM) therapy.

We conducted an oral bromocriptine PK study including healthy postpartum participants during the delivery-associated hospitalization who delivered ≥1 fetus at ≥28 weeks' gestation. Patients on CYP34A inhibitors or inducers, those with clinical contraindications according to the FDA package insert, and those who planned to express breastmilk (given the potential negative effects of bromocriptine on lactation) were excluded. Whole blood was collected pre-dose and 1, 2, 3, 4, 6, 8, and 12 h after an observed dose of 5 mg bromocriptine. Plasma was analyzed using mass spectrometry. Parameters of interest included 12-h area-under-the-curve (AUC₁₂), elimination half-life (t_1/2), maximum concentration (C_max), and time to C_max (T _max).

Non-compartmental PK analysis was conducted on nine participants, demonstrating mean ± SD AUC₁₂, t _1/2, C_max, and T_max were 180 ± 207 pg h/mL, 5.4 ± 4.8 h, 56 ± 64 pg/mL, and 1.6 ± 1.1 h, respectively.

In this modest sample, several PK parameters of oral bromocriptine in healthy postpartum participants differed from those reported in the literature, which may be due to physiological changes in pregnancy. The association between PK parameters and clinical outcomes in patients with PPCM warrants further evaluation.