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Performing the rehabilitation of a player on a surface different from the normally used by the athlete in her/his sport is beneficial. By recruiting more muscle fibers in the new surface, the rehabilitation process is enhanced. Here, we describe the electromyography (EMG) data of anterior and posterior chains during workouts on two different surfaces: sand and artificial turf. We recorded data using a Myontec EMG device of two anterior cruciate ligament (ACL) injured women's soccer players. Player 1 was injured on her left leg in the ACL and the patellar tendon, and player 2 was injured on her right leg in the ACL and semitendinosus plasty. The EMG results of player 1 showed an increase in the activation of the cross pattern (i.e. left hamstring and right gluteus) of the posterior chain. Similarly, the EMG data of player 2 showed an increase in the activation of the left quadriceps (the antagonist muscle of her injured leg) of the anterior chain. In conclusion, in both players the muscle group most activated during rehabilitation was the antagonist of the injured leg's muscle, regardless of the surface used.

Irosustat is a first-generation, irreversible, steroid sulfatase inhibitor currently in development for hormone-dependent cancer therapy. To predict clinical drug-drug interactions between irosustat and possible concomitantly administered medications, the inhibition/induction potential of irosustat with the main drug-metabolizing enzymes was investigated in vitro. The interaction of aromatase inhibitors in the in vitro metabolism of irosustat was also studied. Irosustat inhibited CYP1A2 activity in human liver microsomes through the formation of its desulfamoylated degradation product and metabolite 667-coumarin. CYP1A2 inhibition by 667-coumarin was competitive, with a Kiof 0.77 μM, a concentration exceeding by only 5-fold the maximal steady-state concentration of 667-coumarin in human plasma with the recommended dose of irosustat. In addition, 667-coumarin metabolites enhanced the inhibition of CYP1A2 activity. Additional clinical interaction studies of irosustat with CYP1A2 substrate drugs are strongly recommended. 667-Coumarin also appeared to be a competitive inhibitor of CYP2C19 (Ki= 5.8 μM) in human liver microsomes, and this inhibition increased with assessment in human hepatocytes. Inhibition of CYP2C19 enzyme activity was not caused by repression of CYP2C19gene expression. Therefore, additional mechanistic experiments or follow-up studies with clinical evaluation are recommended. Irosustat neither inhibited CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2D6, CYP2E1, CYP3A4/5, or UDP-glucuronosyltransferase 1A1, 1A4, or 2B7 activities nor induced CYP1A2, CYP2C9, CYP2C19, or CYP3A4/5 at clinically relevant concentrations. Results from human liver microsomes indicated that no changes in irosustat pharmacokinetics in vivo are expected as a result of inhibition of irosustat metabolism in cases of concomitant medication administration or irosustat-aromatase inhibitor combination therapy with letrozole, anastrozole, or exemestane.

Irosustat is a novel steroid sulfatase inhibitor for hormone-dependent cancer therapy. Its structure is a tricyclic coumarin-based sulfamate that undergoes desulfamoylation in aqueous solution, yielding the sulfamoyl-free derivative, 667-coumarin. The aim of the present work was to study the in vitro metabolism of irosustat, including its metabolic profile in liver microsomes and hepatocytes, the potential species differences, and the identification of the main metabolites and of the enzymes participating in its metabolism. Irosustat was extensively metabolized in vitro, showing similar metabolite profiles among rat, dog, monkey, and humans (both sexes). In liver microsomes, the dog was the species that metabolized irosustat most similarly to metabolism in humans. Marked differences were found between liver microsomes and hepatocytes, meaning that phase I and phase II enzymes contribute to irosustat metabolism. Various monohydroxylated metabolites of irosustat and of 667-coumarin were found in liver microsomes, which mostly involved hydroxylations at the C8, C10, and C12 positions in the cycloheptane ring moiety. 667-Coumarin was formed by degradation but also by non-NADPH-dependent enzymatic hydrolysis, probably catalyzed by microsomal steroid sulfatase. The main metabolites formed by hepatocytes were glucuronide and sulfate conjugates of 667-coumarin and of some of its monohydroxylated metabolites. The major cytochrome P450 enzymes involved in the transformation of irosustat were CYP2C8, CYP2C9, CYP3A4/5, and CYP2E1. Moreover, various phase II enzymes (UDP-glucuronosyltransferases and sulfotransferases) were capable of conjugating many of the metabolites of irosustat and 667-coumarin; however, the clinically relevant isoforms could not be elucidated.