Volumetric Absorptive Microsampling During Spaceflight for Analysis of Acetaminophen Pharmacokinetics in Whole Blood

Spaceflight induces altered physiology that has the potential to alter medication pharmacokinetics due to factors including gastrointestinal motility, fluid balance, circulatory dynamics, hormonal changes, and metabolic alterations. Here, we report the first pharmacokinetic analysis using blood samples during spaceflight. The four SpaceX Polaris Dawn crewmembers ingested 500 mg of oral acetaminophen pre-flight, in-flight, and post-flight. Post-ingestion capillary blood samples were collected using volumetric absorptive microsampling (VAMS). Samples were analyzed using liquid chromatography-tandem mass spectrometry. All samples collected in microgravity were adequate for post-flight analysis. Compared to pre-flight baseline, in-flight increases were observed in the C_max (mean [SD] ng/mL: pre-flight = 9110 [3290], in-flight = 43,300 [5700], P < .001), AUC_0-last (mean [SD] h ng/mL: pre-flight = 26,100 [4520], in-flight = 109,000 [29,400]), and λ_z (mean [SD] 1/h: pre-flight = 0.227 [0.0688], in-flight = 0.336 [0.0209]). Compared to pre-flight baseline, in-flight decreases were observed in t_max (mean [SD] h: pre-flight = 1.06 [0.657], in-flight = 0.688 [0.239]), t_1/2 (mean [SD] h: pre-flight = 3.27 [0.950], in-flight = 2.07 [0.130]), CL/F (mean [SD] mL/h: pre-flight = 16,200 [2990], in-flight = 3890 [559]), and V_z/F (mean [SD] mL: pre-flight = 74,700 [18,800], in-flight = 11,500 [1100]). Compared to pre-flight baseline, C_max, AUC, and λ_z increased in-flight, while t_max, t_1/2, V_z/F, and CL/F decreased in-flight. C_max, AUC, V_z/F, and CL/F showed residual changes 3 days post-flight (R + 3). Supratherapeutic blood levels with standard terrestrial dosing raises concern for inadvertent toxicity in the spaceflight environment, and highlights the value of further pharmacokinetic study of medications commonly included within spaceflight medical systems. Overall, VAMS enabled pharmacokinetic study during spaceflight and could serve as a platform for future pharmacokinetic studies.