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Population Pharmacokinetics and Bayesian Estimation of the Area Under the Concentration‐Time Curve for Ganciclovir in Adult Chinese Renal Allograft Recipients After Valganciclovir Administration
Author(s) -
Chen Bing,
Hu ShanShan,
Rui WenBin,
An HuiMin,
Zhai XiaoHui,
Wang XiHan,
Lu JiaQian,
Shao Kun,
Zhou PeiJun
Publication year - 2021
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1002/jcph.1735
Subject(s) - valganciclovir , pharmacokinetics , ganciclovir , medicine , urology , population , cmax , creatinine , pharmacology , immunology , virus , environmental health , human cytomegalovirus
Valganciclovir (VGCV) is the prodrug of ganciclovir (GCV). The objective of this study was to establish a population pharmacokinetic model (PPK) of GCV to investigate the PK characteristics of GCV after administration of VGCV in adult Chinese renal allograft recipients. Seventy Chinese renal allograft recipients were given 450 mg (n = 41) or 900 mg (n = 29) VGCV daily. Blood samples were drawn 0‐24 hours after 5 days’ therapy, and GCV plasma levels were determined. The PPK model was constructed using nonlinear mixed‐effects modeling, and the Bayesian estimation of AUC 0‐24h was constructed for an individual patient based on limited plasma samples. The PK of GCV was best described by a 2‐compartment model with a first‐order absorption process. The CL/F, V 2 /F, Q/F, V 3 /F, K a , and lag time of GCV were 15.8 ± 0.71 L/h, 10.9 ± 2.38 L, 3.98 ± 0.40 L/h, 167 ± 44.0 L, 0.23 ± 0.0078 1/h, and 0.93 ± 0.017 hours, respectively. Clearance of creatinine was found to have a significant impact on the CL/F of GCV ( P < .01). Sampling strategies consisted of plasma concentrations 0 and 2 and 0, 2, and 4 hours after VGCV administration were shown to be suitable for the estimation of the GCV AUC 0‐24h . The PPK model was acceptable and can describe the PK of GCV in Chinese renal transplant patients administered VGCV. The AUC 0‐24h of GCV in Chinese renal transplant patients can be calculated by a limited sampling strategy method.