The purpose of this study was to characterize the relationship between

The purpose of this study was to characterize the relationship between degree of anticoagulation assessed by APTT and the plasma concentration of inogatran in healthy subjects and in individuals with coronary artery disease. were compensated for by including the lower limit of the normal reference range like a covariate influencing both baseline and Emax in the model. For the typical healthy subject and patient the method-corrected populace mean parameters were: APTTbaseline 35 and 31 s slope Levonorgestrel 8.0 and 5.8 s l μmol?1 Emax 36 and 34 s and Estudies have shown the inhibition of thrombin by inogatran is reversible competitive and selective [2]. For this class of drugs it is important that an optimal degree of anticoagulation is definitely attained that gives the desired antithrombotic effect without increasing the risk for adverse effects such as bleeding complications to an unacceptable level. One common surrogate marker for Levonorgestrel the degree of anticoagulation is the triggered partial thromboplastin time (APTT) which has long been used to monitor treatment with heparin [3] and more recently in the medical evaluation of direct thrombin inhibitors e.g. hirudin hirulog and argatroban [4-10]. Restorative ranges for APTT have been founded empirically for heparin in various Levonorgestrel indications [11] but troubles exist due to lack of standardization of measurement methods between laboratories. After incubation of citrated plasma having a reagent comprising phospholipids as a substitute for platelet membranes and a contact activator calcium is definitely added and the clotting time (APTT) is definitely registered. Sources of variation in the APTT result include e.g. type and Levonorgestrel source of reagents including batch-to-batch variations type of instrument used for clot detection citrate concentration in the test tube and type of test tube [12-18]. In addition anticoagulants with differing mechanism of action create different levels of antithrombotic effect and bleeding at the same level of APTT [3 8 19 Antithrombotic effects have been shown for inogatran at plasma concentrations of 0.3-3 μmol l?1 in experimental rat models [20 22 23 The expected therapeutic level is 1 μmol l?1 which is the concentration that causes a two-fold increase of APTT from your baseline when inogatran is added to human being plasma [2]. The aim of this investigation was to characterize the relationship between plasma concentration of inogatran and APTT measured in healthy volunteers and in individuals with coronary artery disease and to identify important factors influencing this relationship. Pharmacodynamic data from seven medical trials involving a total of 1026 individuals were therefore evaluated using the populace approach. Methods Clinical studies Data from five pharmacokinetic studies in 78 healthy volunteers and two medical multicentre studies in 948 individuals with coronary artery disease were included in the analyses. The main design characteristics of the studies are given Mmp24 in Table 1. Levonorgestrel All study protocols were authorized by the relevant ethics committees and the studies were performed according to GCP (Good Clinical Practice) requirements. Written educated consent was acquired prior to enrolment. The pharmacokinetic and medical results from these studies possess previously been reported [24-26]. Table 1 Main study characteristics of i.v. inogatran data included in the populace pharmacodynamic analysis Healthy volunteers Seventy-eight male volunteers judged to be healthy by standard medical and laboratory investigations participated in five phase I pharmacokinetic studies (studies A-E) conducted in the AstraZeneca drug study unit (G?teborg Sweden). Demographic info is definitely summarized in Table 2. A total of 110 administrations of inogatran were given as i.v. infusions over 10 min (studies A-B Levonorgestrel D-E) or 4 h (study C). In addition placebo was given in study C. A total of 1096 pairs of blood samples (3-15 per subject) were drawn for subsequent dedication of..