Responsibility for opinions, conclusions, and interpretation of data lies with the authors. == Conflict of Interest == C.L., T.P., F.P., A.B., J.R., and C.H. (thigh) at this time point. A similar effect on LDL-C levels was seen across the entire time course of the study at all three injection sites. Treatment-emergent adverse events were experienced by 8/20 (stomach), 11/20 (upper arm), and 13/20 (thigh) subjects. There were 2 moderate/transient injection site reactions. There were no serious adverse events. == Conversation == A single subcutaneous administration of alirocumab 75 mg via prefilled pen was well Bakuchiol tolerated with comparable pharmacokinetics and pharmacodynamics when injected into the stomach, upper arm, or thigh. == Conclusion == These results suggest that alirocumab can be interchangeably injected in the stomach, upper arm, or thigh. Keywords:Alirocumab, Cholesterol, Low-density lipoprotein, Pharmacodynamics, Pharmacokinetics, Proprotein convertase subtilisin/kexin type 9 == Introduction == Proprotein convertase subtilisin/kexin type 9 (PCSK9) is usually a protease that mediates degradation of low-density lipoprotein (LDL) receptors1. By its effect of increasing the numbers of LDL receptors, inhibition of PCSK9 is being investigated as a means of reducing levels of LDL cholesterol (LDL-C). Alirocumab is usually a fully human monoclonal antibody that specifically binds to and inhibits PCSK9. In Phase 2 studies, alirocumab administered every 2 weeks at a dose of 150 mg reduced LDL-C by up to 72% when combined with statins ezetimibe, with the most common treatment-emergent adverse event (TEAE) being transient injection site reactions of mild intensity and short duration24. In these studies, all patients received alirocumab injections in the abdomen; however, patients may prefer to use different injection sites. Here, we report the relative pharmacokinetics (PK), pharmacodynamics (PD), and safety Bakuchiol of alirocumab after single subcutaneous (SC) administration of 75 mg into the abdomen, upper arm, and thigh of healthy subjects. == Methods == == Study Design and Population == This was an open-label, randomized, Phase 1 study conducted in healthy subjects aged 1845 years with LDL-C levels >95 mg/dL (2.46 mmol/L) not receiving background lipid-lowering therapy. The study was conducted at the Hammersmith Medicines Research Clinical Research Unit in London, UK (NCT01785329). The protocol was approved by the Scotland A Research Ethics Committee, Edinburgh, Scotland, and written informed consent was obtained from all participants. Subjects were randomized to one of the three parallel groups and received a single 75 mg dose of alirocumab SC via 1-mL prefilled pen at one of the three distinct sites (abdomen, upper arm, and thigh) in the morning on Day 1. Samples for PK and PD analyses (including free PCSK9 and LDL-C assessments) were collected following a 10-h fast predose on Day 1, and at various time points up to Day 85 (2 days, end of the study). The primary objective was to compare the relative PK of a single SC dose of alirocumab 75 mg administered at three different injection sites in healthy subjects. Additional objectives included Bakuchiol assessments of the effect of a single SC dose of alirocumab on serum LDL-C, other lipid parameters, free PCSK9 levels, and safety. Alirocumab and free PCSK9 serum concentrations were determined using validated enzyme-linked immunosorbent assays with lower limits of quantification (LLOQ) of 78 and 31.2 ng/mL, respectively. PK parameters for the systemic exposure of alirocumab, calculated using noncompartmental methods, included maximum serum concentration (Cmax), area under the serum concentration versus time curve (AUC), and AUC from time zero to time of last concentration above LLOQ (AUClast). LDL-C was calculated using Bakuchiol the Friedewald formula5. Total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), triglycerides (TGs), apolipoprotein (apo) B, and apoA1 were measured directly. Safety assessments included TEAEs, especially local tolerability (injection site reactions). TEAEs were defined as any AE occurring from the time of alirocumab Rabbit Polyclonal to MYB-A administration up to the end of the study visit. ==.