Pharmacology Space Kit (PSK) - Dried Blood Spot for Caffeine Pharmacokinetics Under Microgravity Conditions

The PSK study is preliminary to the study of drug metabolism in space flight conditions. The investigators propose to use simplified blood sampling methods that can be applied in microgravity. This method is based on the use of capillary blood, obtained using an automatic lancet for diabetics, the blood droplet then being deposited on specific blotting paper, and then studied in the laboratory. In 2022, the investigators validated the transfer of artificial blood in parabolic flight conditions, as well as the validity of cardiovascular drug dosage.

The objective of the 2023 study is to validate the collection and transfer of capillary blood, on themselves, by healthy volunteers with little training, for the blood dosage of caffeine after intake of standard doses of alimentary caffeine.

The primary objective is a feasibility of 90% of sampling in microgravity, compared with 95% on ground. Secondary objectives are the pharmacokinetic of different forms of caffeine, according to genetic background and other modifiers of CYP1A2.

The investigators propose to use simplified blood sampling methods that can be applied in microgravity. This method is based on the use of capillary blood, obtained using an automatic lancet for diabetics, the blood droplet then being deposited on specific blotting paper, and then studied in the laboratory.

The objective of the study is to validate the collection and transfer of capillary blood from finger prick test, performed on themselves, by healthy volunteers after a short training, for the blood dosage of caffeine. Dietary caffeine will be used, issued from standardized espresso, tea or dark chocolate.

Caffeine is a universally used food substance and is metabolised by a pathway common to many drugs (CYP 1A2). The aim is to show that it is possible to collect blood in this way, and to carry out assays of caffeine. Secondary objectives are to assess the kinetics of caffeine metabolism through the metabolic ratio (AUC paraxanthine/AUC caffeine), and to correlate these kinetics with genetic variations in CYP 1A2 activity.

Participants are healthy volunteers already selected to take part in the parabolic flight campaign.

A success rate of 95% for ground sampling, and 90% for in-flight sampling is assumed as satisfactory. If 5 volunteer participants during the 3 days of flying carry out 2 in-flight samplings, this results in 30 in-flight samplings. If the other 25 flying volunteers take only one in-flight sample, means 25 in-flight samples (total 55). On the ground, the 30 volunteers will take 90 samples, for a total of 145 minimum samples. An equivalence threshold for a maximum 20% difference between flight and ground conditions is considered. For a difference of 10, 15 and 20%, the power is 34, 79 and 97% respectively. It can therefore conclude that the difference between the two sampling conditions is not clinically significant.

Eligibility Criteria:
Inclusion Criteria:

* Be affiliated to a social security scheme or benefit from such a scheme.
* Have obtained a medical certificate stating that they are fit for parabolic flights.
* Be aged between 18 and 70
* Be in good health: no chronic treatment that could interact with the metabolism of caffeine, no progressive disease
* Must not have any contraindications to taking caffeine (30 to 100 mg). Volunteers will also be asked not to consume caffeine (coffee, chocolate, energy drinks, tea, cola, etc.) in the 24 hours preceding the experiment.

Exclusion Criteria:

* Be the subject of a legal protection measure (safeguard of justice, curatorship or guardianship)
* suffer from haematophobia (irrational fear of blood)
* Have a current infectious disease, particularly viral
* Have an active chronic illness
* Have a high usual intake of caffeine (\>4 espressos, \>4 cups of tea, \>100g dark chocolate per day)
* Total intolerance to all forms of caffeine
* Smoke more than 20 cigarettes a day
* Have weaned themselves off smoking for less than a month
* Have a history of severe Raynaud's phenomenon
* Have a history of naupathy
* Suffering from naupathy during a flight