Pharmacokinetics of metoprolol during pregnancy and lactation

摘要: The objective of this study was to evaluate the steady-state pharmacokinetics metoprolol during pregnancy and lactation. Serial plasma, urine, breast milk concentrations its metabolite, α-hydroxymetoprolol, were measured over 1 dosing interval in women treated with (25-750 mg/day) early (n = 4), mid-pregnancy (n = 14), late (n = 15), as well postpartum (n = 9) (n = 4) without (n = 5) Subjects genotyped for CYP2D6 loss-of-function allelic variants. Using paired analysis, mean apparent oral clearance significantly higher (361 ± 223 L/h, n = 5, P < .05) (568 ± 273 n = 8, compared ≥3 months (200 ± 131 192 ± 98 respectively). When comparison limited extensive metabolizers (EMs), both mid- (P < .05). Relative infant exposure through <1.0% maternal weight-adjusted dose (n = 3). Because large, pregnancy-induced changes pharmacokinetics, if inadequate clinical responses are encountered, clinicians who prescribe should be prepared make aggressive dosage (dose frequency) or consider using an alternate beta-blocker.