\n\nObjective: The primary study objective Tozasertib was to determine the effect of vicriviroc, a C-C chemokine receptor type 5 inhibitor, alone or in the presence of ritonavir, on the pharmacokinetics (AUG and C(max)) of
the study OC (ethinyl estradiol [EE] 0.035 mg + norethindrone [NET] 1 mg). A secondary objective was to monitor the safety and tolerability of vicriviroc plus an OC with and without ritonavir.\n\nMethods: This was a randomized, open-label, parallel-group, single-center study with a fixed-sequence crossover design. Female subjects were randomized into 2 groups and treated for 2 menstrual cycles. In cycle 1, all received AZD8055 the OC alone, per standard 28-day pack instructions. On the first 10 days of cycle 2, group 1 received OC + vicriviroc and group 2 received OC + ritonavir; on the following 11 days, both groups received OC + vicriviroc
+ ritonavir. Blood samples were collected up to 24 hours after dosing on prespecified days. Pharmacokinetic parameters, including AUC(0-2)4, C(max), and C(min), were calculated using non-compartmental methods, and drug interactions were evaluated using an ANOVA model by treatment group. Adverse events were collected using physical examination, vital sign measurements, clinical laboratory analysis, electrocardiography, and questioning at predefined time points throughout the study to assess the safety profile.\n\nResults: Twenty-seven subjects were enrolled (26 white, 1 black). The median age and body mass index were 21 years (range, 18-36 years) and 24.5 kg/m(2) (range, 19.1-31.3 kg/m(2)), respectively. Twenty-one subjects completed the study and were included in the pharmacokinetic analysis; 4 discontinued for reasons unrelated
to study drug and 2 discontinued because of adverse events. Vicriviroc had little effect on the pharmacokinetics of the OC. EE mean ratio estimates for C(max) and AUC(0-24) compared with OC administered alone were 91% and 97%, respectively, and for NET were 106% and 93%. Subjects receiving ritonavir, alone or with vicriviroc, experienced decreases in exposure {Selleck Anti-diabetic Compound Library|Selleck Antidiabetic Compound Library|Selleck Anti-diabetic Compound Library|Selleck Antidiabetic Compound Library|Selleckchem Anti-diabetic Compound Library|Selleckchem Antidiabetic Compound Library|Selleckchem Anti-diabetic Compound Library|Selleckchem Antidiabetic Compound Library|Anti-diabetic Compound Library|Antidiabetic Compound Library|Anti-diabetic Compound Library|Antidiabetic Compound Library|Anti-diabetic Compound Library|Antidiabetic Compound Library|Anti-diabetic Compound Library|Antidiabetic Compound Library|Anti-diabetic Compound Library|Antidiabetic Compound Library|Anti-diabetic Compound Library|Antidiabetic Compound Library|Anti-diabetic Compound Library|Antidiabetic Compound Library|Anti-diabetic Compound Library|Antidiabetic Compound Library|Anti-diabetic Compound Library|Antidiabetic Compound Library|buy Anti-diabetic Compound Library|Anti-diabetic Compound Library ic50|Anti-diabetic Compound Library price|Anti-diabetic Compound Library cost|Anti-diabetic Compound Library solubility dmso|Anti-diabetic Compound Library purchase|Anti-diabetic Compound Library manufacturer|Anti-diabetic Compound Library research buy|Anti-diabetic Compound Library order|Anti-diabetic Compound Library mouse|Anti-diabetic Compound Library chemical structure|Anti-diabetic Compound Library mw|Anti-diabetic Compound Library molecular weight|Anti-diabetic Compound Library datasheet|Anti-diabetic Compound Library supplier|Anti-diabetic Compound Library in vitro|Anti-diabetic Compound Library cell line|Anti-diabetic Compound Library concentration|Anti-diabetic Compound Library nmr|Anti-diabetic Compound Library in vivo|Anti-diabetic Compound Library clinical trial|Anti-diabetic Compound Library cell assay|Anti-diabetic Compound Library screening|Anti-diabetic Compound Library high throughput|buy Antidiabetic Compound Library|Antidiabetic Compound Library ic50|Antidiabetic Compound Library price|Antidiabetic Compound Library cost|Antidiabetic Compound Library solubility dmso|Antidiabetic Compound Library purchase|Antidiabetic Compound Library manufacturer|Antidiabetic Compound Library research buy|Antidiabetic Compound Library order|Antidiabetic Compound Library chemical structure|Antidiabetic Compound Library datasheet|Antidiabetic Compound Library supplier|Antidiabetic Compound Library in vitro|Antidiabetic Compound Library cell line|Antidiabetic Compound Library concentration|Antidiabetic Compound Library clinical trial|Antidiabetic Compound Library cell assay|Antidiabetic Compound Library screening|Antidiabetic Compound Library high throughput|Anti-diabetic Compound high throughput screening| of EE (C(max) mean ratio estimates, 89% and 76%; AUC(0-24) mean ratio estimates, 71% each, for ritonavir alone and ritonavir with vicriviroc, respectively) and, to a lesser extent, decreases in NET (Cmax mean ratio estimates 89% each; AUC(0-24) mean ratio estimates: 93% and 83%, for ritonavir alone and ritonavir with vicriviroc, respectively). Twenty-two of 27 (81%) subjects reported >= 1 treatment-emergent adverse event (TEAE). During cycle 1, TEAEs were reported for 18 of 27 (67%) subjects while receiving OC alone and for 3 of 24 (13%) subjects while receiving placebo OC.