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...
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2025-01-01
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| Series: | Clinical and Translational Science |
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| Online Access: | https://doi.org/10.1111/cts.70113 |
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| author | Liva K. Stuhr Joshua B. Feinberg Thea Christoffersen Konstantinos Dimopoulos Mikkel B. Christensen David P. Sonne Troels Riis Peter S. Plomgaard Jens P. Goetze Emil L. Larsen Kristian Karstoft |
| author_facet | Liva K. Stuhr Joshua B. Feinberg Thea Christoffersen Konstantinos Dimopoulos Mikkel B. Christensen David P. Sonne Troels Riis Peter S. Plomgaard Jens P. Goetze Emil L. Larsen Kristian Karstoft |
| author_sort | Liva K. Stuhr |
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| description | 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. |
| format | Article |
| id | doaj-art-66a31e34c1934a6693d9603d980cbe71 |
| institution | Kabale University |
| issn | 1752-8054 1752-8062 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Wiley |
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| series | Clinical and Translational Science |
| spelling | doaj-art-66a31e34c1934a6693d9603d980cbe712025-01-24T08:17:46ZengWileyClinical and Translational Science1752-80541752-80622025-01-01181n/an/a10.1111/cts.70113The Effect of Exercise on Pharmacodynamics and Pharmacokinetics of a Single Dose of Unfractionated Heparin—A Randomized, Controlled, Crossover StudyLiva K. Stuhr0Joshua B. Feinberg1Thea Christoffersen2Konstantinos Dimopoulos3Mikkel B. Christensen4David P. Sonne5Troels Riis6Peter S. Plomgaard7Jens P. Goetze8Emil L. Larsen9Kristian Karstoft10Department of Clinical Pharmacology Copenhagen University Hospital – Bispebjerg and Frederiksberg Copenhagen DenmarkDepartment of Clinical Pharmacology Copenhagen University Hospital – Bispebjerg and Frederiksberg Copenhagen DenmarkDepartment of Clinical Pharmacology Copenhagen University Hospital – Bispebjerg and Frederiksberg Copenhagen DenmarkDepartment of Clinical Biochemistry Copenhagen University Hospital – Bispebjerg and Frederiksberg Copenhagen DenmarkDepartment of Clinical Pharmacology Copenhagen University Hospital – Bispebjerg and Frederiksberg Copenhagen DenmarkDepartment of Clinical Pharmacology Copenhagen University Hospital – Bispebjerg and Frederiksberg Copenhagen DenmarkDepartment of Clinical Pharmacology Copenhagen University Hospital – Bispebjerg and Frederiksberg Copenhagen DenmarkThe Centre for Physical Activity Research Rigshospitalet Copenhagen DenmarkDepartment of Clinical Biochemistry Rigshospitalet Copenhagen DenmarkDepartment of Clinical Biochemistry Rigshospitalet Copenhagen DenmarkDepartment of Clinical Pharmacology Copenhagen University Hospital – Bispebjerg and Frederiksberg Copenhagen DenmarkABSTRACT 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.https://doi.org/10.1111/cts.70113bioavailabilityexercisepharmacodynamicspharmacokineticsunfractionated heparin |
| spellingShingle | Liva K. Stuhr Joshua B. Feinberg Thea Christoffersen Konstantinos Dimopoulos Mikkel B. Christensen David P. Sonne Troels Riis Peter S. Plomgaard Jens P. Goetze Emil L. Larsen Kristian Karstoft The Effect of Exercise on Pharmacodynamics and Pharmacokinetics of a Single Dose of Unfractionated Heparin—A Randomized, Controlled, Crossover Study Clinical and Translational Science bioavailability exercise pharmacodynamics pharmacokinetics unfractionated heparin |
| title | The Effect of Exercise on Pharmacodynamics and Pharmacokinetics of a Single Dose of Unfractionated Heparin—A Randomized, Controlled, Crossover Study |
| title_full | The Effect of Exercise on Pharmacodynamics and Pharmacokinetics of a Single Dose of Unfractionated Heparin—A Randomized, Controlled, Crossover Study |
| title_fullStr | The Effect of Exercise on Pharmacodynamics and Pharmacokinetics of a Single Dose of Unfractionated Heparin—A Randomized, Controlled, Crossover Study |
| title_full_unstemmed | The Effect of Exercise on Pharmacodynamics and Pharmacokinetics of a Single Dose of Unfractionated Heparin—A Randomized, Controlled, Crossover Study |
| title_short | The Effect of Exercise on Pharmacodynamics and Pharmacokinetics of a Single Dose of Unfractionated Heparin—A Randomized, Controlled, Crossover Study |
| title_sort | effect of exercise on pharmacodynamics and pharmacokinetics of a single dose of unfractionated heparin a randomized controlled crossover study |
| topic | bioavailability exercise pharmacodynamics pharmacokinetics unfractionated heparin |
| url | https://doi.org/10.1111/cts.70113 |
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