Feasibility of dried blood spot collection for caffeine pharmacokinetic studies in microgravity: Insights from parabolic flight campaigns
Authors: Derobertmasure Audrey , Toh Li Shean , Verstuyft Céline , Lukic Srboljub , De Sousa Carvalho Christelle , Couronné Raphaël , Beauvalet Marie , Chhun Stéphanie , Boutouyrie Pierre 
Published: October 2024

Aims

Therapeutic drug monitoring for astronauts faces limitations in conventional blood sampling and sample management onboard the international space station. Here, we explore the feasibility of dried blood spot (DBS) collection during parabolic flights (PF) to overcome these constraints.

Methods

We assessed the feasibility of blood deposition on blotting paper for preanalytical aspects in a PF using synthetic blood. Subsequently, DBS sampling validation was carried out in another PF campaign. Twenty volunteers participated in a pharmacokinetic study on caffeine and its metabolite, paraxanthine, conducted during parabolic flights. After >18 h caffeine washout, coffee (115 mg), tea (30 mg) or dark chocolate (11 mg) were ingested by the participants. DBS samples were collected at baseline, during weightlessness and post‐flight. Caffeine and paraxanthine were analysed using liquid chromatography–tandem mass spectrometry (LC‐MS/MS). Genotyping for cytochrome P450‐1A2 (CYP1A2) was performed and a metabolic ratio by area under the curve for caffeine and paraxanthine (AUCPAX/AUCCAF) for CYP1A2 was determined. A user experience survey was also conducted.

Results

Full in‐flight pharmacokinetic study was feasible in seventeen volunteers with three unable to perform the sampling due to motion sickness. Nineteen participants (twelve males and seven females) completed pharmacokinetic profiles, with repeated pharmacokinetic studies for six participants. CYP1A2 genotyping resulted in eight ultrarapid, eleven intermediate, and one poor metabolizer. Among the women, four were on oestrogen contraceptives, a known inhibitor of CYP1A2, and were considered as poor metabolizers. Expected differences in kinetic profiles, consistent with consumption habits, the ingested dose and the genotypic/phenotypic information, were observed. The mean caffeine AUC for coffee, tea and chocolate were 9419 ng.h.mL−1 (95% confidence interval [CI]: 6222–12 616, n = 10), 6917 ng.h.mL−1 (95% CI: 2729–11 105), n = 7) and 3039 ng.h.mL−1 (95% CI: 1614–4142, n = 12), respectively. The mean paraxanthine AUC were 10 566 ng.h.mL−1 (95% CI: 6242–14 890, n = 10), 4011 ng.h.mL−1 (95% CI: 2305–5716, n = 7) and 3638 ng.h.mL−1 (95% CI: 1589–40 859, n = 12), respectively. The mean metabolic ratio in oestrogen‐treated women was 0.53 (95% CI: 0.35–0.71) compared to 1.19 (95% CI: 0.99–1.33) in others. The mean metabolic ratio was 1.02 (95% CI: 0.81–1.23, n = 15) on the ground and 1.10 (95% CI: 0.70–1.41, n = 13) during the parabolic flights, with no significant difference observed between the two conditions. Overall participants were satisfied with the usability of the method.

Conclusions

DBS collection was safe, stable, feasible and well accepted in weightlessness. This method would offer valuable insights into human metabolism adaptation during long‐term spaceflight, addressing space pharmacology challenges.