Influence of Tocolytical Medications on Hemodynamics (Central and Peripheral) and Vascular Function in a Pilot Study to Determine the Design of the Final Study and the Final Study Itself

Pilot Study: A Dose-Response Finding Study of Ritodrine (Pre-Par®) to Find the Highest Well Tolerated Dose in Young, Healthy, Female Volunteers. To Find the Size-Order of the Hemodynamical Effects of Ritodrine (PrePar®) and Atosiban (Tractocile®) to Determine the Relevance of a PK/PD-Modelling in the Final Study. Final Study: Investigating the Influence of Tocolytical Medications: Ritodrine (PrePar®) and Atosiban (Tractocile®) at the Clinical Dose on the Hemodynamics and Arterial Function in Healthy Female Volunteers, Compared to Placebo During Continuous Intravenous Infusion.

This trial will consist of two parts:

A pilot study in a three-way cross over trial to determine the highest well tolerated dose of Ritodrine (Pre-Par®), the impact of Atosiban (Tractocile®) on the hemodynamics and hence the design of the final study.

The final study is planned as a three-way crossover trial to investigate and compare the cardiovascular effects of Ritodrine, Atosiban and placebo to relate those effects to the pharmacokinetics of Ritodrine and Atosiban (PK/PD modelling).

Inclusion Criteria:

• Age between 20 and 40 years old;
• In good health, especially no cardiovascular diseases, obstructive lung diseases, chronic kidney diseases or diabetes mellitus.
• Using a proper anticonception method (orally, subcutaneously);
• A negative pregnancy test.

Exclusion Criteria:

• Intolerance of Ritodrine;
• On chronic medication, except oral and subcutaneous contraception
• History or present presentation of cardiac arrythmias;
• Risk of being pregnant or less than 6 months postpartum;
• Giving breastfeeding;
• Previous uteral surgery;
• Using an intra-uteral device (IUD);
• A severe addiction: nicotine (> 10 cigarettes/day), alcohol (> 3 units/day), caffeine (> 5 units/day) or any extralegally drugs.