The Effect Of Exercise On Pharmacodynamics And Pharmacokinetics Of A Single Dose Of Unfractionated Heparin

BACKGROUND: Exercise increases blood and lymph flow in working muscles, which may affect the pharmacokinetics and, secondarily to this, pharmacodynamics of parenterally administered drugs. PURPOSE: The aim of this study was to assess the influence of a single exercise session on pharmacokinetics and pharmacodynamics of a single dose of subcutaneous (sc) administered unfractionated heparin (UFH). METHODS: Fifteen healthy male individuals underwent 4 experimental days where 15,000 IE of UFH was injected sc in the thigh of the non-dominant leg. Following the injection, one of 4 interventions was performed pr. day: 1) no exercise, 2) double-legged bicycle exercise, 3) single-legged bicycle exercise with the non-dominant leg and 4) single-legged bicycle exercise with the dominant leg. Exercise bouts were 60 minutes and of moderate intensity. Blood samples were drawn during and after the interventions, and subsequently analyzed for activated partial thromboplastin time (aPTT) and plasma heparin, measured by an anti-factor Xa assay. RESULTS: All individuals completed all interventions. Single-legged exercise interventions were identical with regards to exercise intensity (Watt). Preliminary data (currently 5 subjects) shows a greater increase in aPTT (peak minus baseline value) following an intervention of double-legged exercise compared to no exercise (4.7 ± 6.6 vs 3.1 ± 4.3 [mean ± SD). Furthermore, the increase in aPTT following the single-legged exercise with UFH in the exercising leg, was greater compared to the session with UFH in the non-exercising leg (6.7 ± 13.4 vs 4.3 ± 11.8), (currently 4 subjects). The full data set, including plasma heparin analyses, will be presented at the conference. CONCLUSION: Preliminary data suggest that exercise increases the pharmacological effect of sc administered UFH. The single-leg interventions suggests that the effect was directly due to increased uptake of UFH with exercise. As such, exercise is a factor that may affect the clinical effects of sc administered drugs. Novo Nordisk Foundation