Bioavailability of Amoxicillin Dissolved in Human Milk
Condition: Healthy
Study type: Interventional
Phase: Phase 2

Summary: 
      The investigators propose to study amoxicillin absorption in a 2-stage program that will
      progressively produce, for the first time, information leading to pediatric pharmacology
      recommendations for the administration to children of amoxicillin dissolved in human milk.
      The investigators study will enroll adult volunteers as number of blood extractions, volume
      of blood required and subject availability, among other issues, generate a number of ethical
      and logistical constraints that make it almost impossible to carry such an intensive sampling
      study in infants.
    

Detailed description: 
      As recommended by the Expert Committee on Selection and Use of Essential Medicines, WHO
      (http://www.who.int/selection_medicines/committees/en/index.html), oral solid formulations
      are the preferred forms of medicines for children, especially in developing countries,
      because of relatively inexpensive and less complicated manufacturing, transporting and
      storage processes. Whereas solid dosage forms are advantageous in these pharmaceutical
      logistics, administering solid formulations to infants and children is a challenging issue.
      Dissolving medicines in water may be acceptable, but safety of drinking water for infants in
      developing countries and water solubility of the drug itself are major concerns. These
      challenges are exemplified in the treatment of infectious diseases and diarrhea in infants.
      Commonly used drugs for infants in low income settings include antibiotics such as
      amoxicillin. Expert sources have suggested that drug administration in breast milk may be
      effective. However, little data is currently available to support the recommendation to
      administer medications dissolved in breast milk to infants.

      The second stage of the project will use the information obtained from the first stage,
      combined with pre-existing data, to define a rational dosing schedule of the target drug
      dissolved in human milk for young children, using population PK modeling and simulation. This
      is a study in silico.
    

Intervention name(s): Human milk-dissolved amoxicillin; Water-dissolved amoxicillin
Intervention type(s): Drug; Drug
Intervention description(s): An amoxicillin suspension bottle containing 5 grams of amoxicillin (powder) will be resuspended in 60 ml of breast milk to have 100mL of a 50mg/mL suspension.; An amoxicillin suspension bottle containing 5 grams of amoxicillin (powder) will be resuspended in 60 ml of water to have 100mL of a 50mg/mL suspension.
Other intervention name(s): Novamoxin 250 from Novopharm, Toronto, Canada: Lot#35422063A; Frozen human milk was obtained from the Mother's Milk Bank of Ohio (USA); Novamoxin 250 from Novopharm, Toronto, Canada: Lot#35422063A
Intervention MeSH terms: Amoxicillin
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: Participants underwent 2 arms in a cross-over design: 1 ) amoxicillin disolved in water; and 2) amoxicillin dissolved in human milk. The order of the 2 arms were randomized.
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: healthy adult volunteers; comparative bioavailability; amoxicillin; breast milk; Amoxicillin Bioavailability in breast milk