title: Hydromorphone transfer into breast milk after intranasal administration.
abstract: OBJECTIVE
  To determine the distribution of hydromorphone into breast milk and the potential exposure of the suckling infant, and whether the distribution of hydromorphone into milk can be predicted accurately by a passive diffusion model.
  
  
  METHODS
  Single-dose, pharmacokinetic study.
  
  
  METHODS
  University clinical research unit.
  
  
  METHODS
  Eight lactating, nonsmoking, healthy women aged 24-32 years.
  
  
  METHODS
  Hydromorphone HCl 2 mg was given intranasally to the women to characterize its pharmacokinetics and extent of its transfer into breast milk.
  
  
  RESULTS
  Plasma and milk samples were analyzed using liquid chromatography with tandem mass spectrometry detection. The milk:plasma ratio (M:P) was calculated as the total area under the concentration-time curve (AUC) of the milk divided by the total AUC of the plasma. Predicted in vitro M:P ratios were calculated using a diffusion model. Protein binding in milk and plasma, partitioning into milk fat (whole milk:skim milk ratios), as well as pH partitioning between plasma and milk were incorporated in the model. Protein binding was determined by equilibrium dialysis. Protein binding was minimal in both milk and plasma, with unbound fractions of 1 and 0.84, respectively There was little partitioning into milk fat, as demonstrated by the whole milk:skim milk ratio of 0.98. The observed and predicted M:P ratios +/- SD for hydromorphone were 2.57 +/- 0.47 and 1.11 +/- 0.28, respectively. The 95% confidence interval for the observed M:P ratio overlapped the confidence interval of the predicted M:P ratio, a finding that supports a role for both passive diffusion and active transport as mechanisms of hydromorphone transfer into milk.
  
  
  CONCLUSIONS
  Hydromorphone distributes rapidly from plasma into breast milk; however, the drug does not partition into fat. The suckling infant would receive approximately 0.67% of the maternal dose of hydromorphone (adjusted for body weight). As this is a limited exposure, further studies are needed to determine any potential impact to an infant who is fed breast milk from a mother treated with hydromorphone.
authors.affiliation: Graduate Center for Toxicology, College of Pharmacy, University of Kentucky, Lexington 40536-0082, USA.
authors.forename: Jeffrey E
authors.initials: JE
authors.lastname: Edwards
authors.forename: Anita C
authors.initials: AC
authors.lastname: Rudy
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Wermeling
authors.forename: Nirmala
authors.initials: N
authors.lastname: Desai
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: McNamara
mesh_terms: D000281:Administration, Intranasal; D000328:Adult; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001942:Breast Feeding; D005260:Female; D006801:Humans; D004091:Hydromorphone / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D008895:Milk, Human / Q000378:metabolism*
chemical_list: D000701:Analgesics, Opioid; D004091:Hydromorphone