The Effect of Exercise on Pharmacodynamics and Pharmacokinetics of a Single Dose of Unfractionated Heparin—A Randomized, Controlled, Crossover Study

ABSTRACT Exercise increases blood and lymph flow in working muscles, potentially affecting the bioavailability and effect of subcutaneously administered drugs. The aim of this study was to assess the influence of a single exercise session on pharmacokinetics and pharmacodynamics of a single dose of subcutaneously administered unfractionated heparin. In a crossover design, 15 healthy males underwent four experimental days where 15,000 IU of unfractionated heparin was injected subcutaneously into the thigh of the non‐dominant leg. Following the injection, one of four interventions was performed in randomized order on four separate occasions, each lasting 1 h: (1) no exercise, (2) double‐legged exercise, (3) single‐legged exercise with the non‐dominant leg (where heparin was injected), and (4) single‐legged exercise with the dominant leg. Blood was sampled during and after the interventions and analyzed for activated partial thromboplastin time (aPTT) and plasma heparin via an anti‐factor Xa assay. The primary endpoint (maximum aPTT minus baseline aPTT) showed no statistically significant differences between interventions, nor did maximum minus baseline plasma heparin activities. However, after 1 h, change in aPTT was greater, following double‐legged exercise compared with no exercise (mean difference 3.5 s, 95% CI 0.8–6.2) and greater after single‐legged exercise with the non‐dominant leg compared with the dominant (9.7 s, 3.9–15.5). Similar results were observed for plasma heparin activities. In conclusion, exercise does not affect the overall pharmacokinetics and pharmacodynamics of unfractionated heparin but tends to accelerate absorption and hence effect. The study thus underscores that physical exercise affects temporal uptake of subcutaneously administered therapy.