Conditions: Healthy
Keywords: healthy adult volunteers comparative bioavailability amoxicillin breast milk Amoxicillin Bioavailability in breast milk
Allocation: RANDOMIZED | Intervention model: CROSSOVER
Enrollment: 16
Healthy volunteers: yes

Brief 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.

Arms:
arm 1: Amoxicillin 500 mg was dissolved in 10 ml water and orally administered in a fasting state. arm 2: Amoxicillin 500 mg was dissolved in 10 ml human milk and orally administered in a fasting state.

Interventions: intervention 1: Human milk-dissolved amoxicillin intervention 2: Water-dissolved amoxicillin
Intervention descriptions: intervention 1: 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. intervention 2: 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.

Protocol document: