Phoenix winnonlin software

PD endpoints included ANC and CD34⁺ cell count. Blood samples for ANC were collected at 0, 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, and 48 h postdose and on days 4, 5, 6, 7, 11, 15, and 22. On the other hand, blood samples for CD34⁺ cell count were collected at predose, 24 and 48 h postdose and on days 4, 5, 6, 7, 11, 15, and 22. The maximum serum concentration of ANC (ANC_max) and CD34⁺ cell count (CD34⁺_max) and time to reach peak ANC (T_{max_ANC}) and CD34⁺ cell count (T_{max_CD34+}) were derived from the observed values. The mean area under the effect-time curve (AUEC_last) was calculated as the area under the PD response curve from time zero to the last observed value using the linear trapezoidal rule. For each of ANC and CD34⁺ cell count, the derived parameters were calculated using the Phoenix WinNonlin software (Professional version 5.1; Pharsight Corporation).

Blood samples were obtained to determine serum eflapegrastim and pegfilgrastim concentrations at 0, 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, and 48 h and on days 4, 5, 6, 7, 11, 15, and 22. Individual PK parameters of eflapegrastim and pegfilgrastim were obtained by noncompartmental methods using the Phoenix WinNonlin software (Professional version 5.1; Pharsight Corporation, Mountain View, CA, USA). The maximum serum concentration (C_max) and time to reach C_max (T_max) were acquired directly from the observed values. AUC from time zero to the last observed concentration (AUC_last) was calculated using the linear trapezoidal method. The terminal elimination half‐life (t_½) was ln(2) divided by the apparent terminal elimination rate constant (λ_z), which was estimated by linear regression of the terminal linear portion of the log concentration versus time curve. The AUC from time zero to infinity (AUC_∞) was the sum of AUC_last and C_last/λ_z, where C_last was the last observed concentration. The apparent clearance (CL/F) was the dose divided by AUC_∞.

The concentration-time data of meloxicam in each pigeon were analyzed using a noncompartmental method in Phoenix WinNonLin software (Version 8.1; Pharsight, Cary, NC), and the resulting pharmacokinetic parameters were obtained. To calculate the first-order rate constant associated with the terminal phase (λz), linear regression was used, and from this, the terminal half-life (t_1/2λz) was determined as ln2/λz. The area under the concentration-time curve (AUC) and the first moment curve (AUMC) were both calculated using the linear trapezoidal rule with extrapolation to time infinity (Chen et al., 2023 (link)). The mean residence time (MRT) was obtained by dividing AUMC_0–∞ by AUC_0–∞. The initial concentration (C₀) after IV administration was estimated using the back extrapolation method. Total body clearance (Cl) was calculated as the ratio of intravenous dose to AUC (Yang et al., 2019 ), while the volume of distribution (V_Z) was determined as V_Z = Dose/AUC/λz, where Dose represented the intravenous dose. The volume of distribution at steady-state (V_SS) was calculated as V_SS = MRT_IV × Cl. After administration via PO and IM routes, the peak concentration (C_max) and time to reach it (T_max) were observed. While the mean absorption time (MAT) was determined as MRT_PO/IM minus MRT_IV (Bello et al., 2022 ). Bioavailability (F) was calculated as the ratio of extravascular AUC to the IV AUC.