Population Pharmacokinetics and Dose Optimization of Ganciclovir in Critically Ill Children

Üney

Vet Pharm & Therapeutics

et al. 2021

The aim of the study was to determine the effect of ketoprofen (2 mg/kg) on the intravenous pharmacokinetics of ganciclovir (10 mg/kg) in chukar partridges (Alectoris chukar). Eight clinically healthy partridges were used in the study. The study was performed in two periods using a cross‐over design following a 15‐day drug washout period. Plasma concentrations of ganciclovir were determined using the high‐pressure liquid chromatography‐ultraviolet detector and analyzed by non‐compartmental analysis. The elimination half‐life (t1/2ʎz), area under the concentration‐time curve (AUC0‐∞), total body clearance, and volume of distribution at steady state of ganciclovir were 1.63 h, 33.22 h*μg/ml, 0.30 L/h/kg, and 0.53 L/kg, respectively. Ketoprofen administration increased the t1/2ʎz and AUC0‐∞ of ganciclovir by 78% and 108%, respectively, and while decreased ClT by 53%. The increased plasma concentration and prolonged elimination half‐life of ganciclovir caused by ketoprofen may result in the prolonged duration of action and therapeutic effect of ganciclovir. However, the concomitant use requires determination of the pharmacokinetics of ketoprofen and the safety of both drugs.

Section: Methodssupporting

confidence: 90%

Effect of ketoprofen on intravenous pharmacokinetics of ganciclovir in chukar partridges (Alectoris chukar)

Üney

Vet Pharm & Therapeutics

et al. 2021

“…The characteristics of each study are summarized in Table 2 . Twelve of the sixteen studies were prospective [ 8 , 11 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 ] and four studies were retrospective [ 9 , 10 , 28 , 29 ]. The number of subjects ranged from 8 to 105, with only two studies with less than 10 subjects [ 8 , 24 ].…”

Section: Resultsmentioning

confidence: 99%

Establishment and Evaluation of a Parametric Population Pharmacokinetic Model Repository for Ganciclovir and Valganciclovir

et al. 2023

Background: Ganciclovir and valganciclovir are used for prophylaxis and treatment of cytomegalovirus infection. However, there is great interindividual variability in ganciclovir’s pharmacokinetics (PK), highlighting the importance of individualized dosing. To facilitate model-informed precision dosing (MIPD), this study aimed to establish a parametric model repository of ganciclovir and valganciclovir by summarizing existing population pharmacokinetic information and analyzing the sources of variability. (2) Methods: A total of four databases were searched for published population PK models. We replicated these models, evaluated the impact of covariates on clearance, calculated the probability of target attainment for each model based on a predetermined dosing regimen, and developed an area under the concentration–time curve (AUC) calculator using maximum a posteriori Bayesian estimation. (3) Results: A total of 16 models, one- or two-compartment models, were included. The most significant covariates were body size (weight and body surface area) and renal function. The results show that 5 mg/kg/12 h of ganciclovir could make the AUC0–24h within 40–80 mg·h/L for 50.03% pediatrics but cause AUC0–24h exceeding the exposure thresholds for toxicity (120 mg·h/L) in 51.24% adults. (4) Conclusions: Dosing regimens of ganciclovir and valganciclovir should be adjusted according to body size and renal function. This model repository has a broad range of potential applications in MIPD.

“…In many studies, the combination of naproxen and other agents with a typical OCT2 substrate (cimetidine) increased the plasma concentration of cimetidine, thereby separately increasing the toxicity of cimetidine [ 29 ]. Ganciclovir [ 30 ], its pharmacokinetic behavior in some studies [ 31 , 32 ], and part of its MATE1 inhibitors or substrate share, showed no significant change in pharmacokinetics parameters, which may be related to other excretory pathways in the body [ 33 ]. In addition, this paper also examines the ligation of the bilateral renal compensatory, where the transporter will affect the elimination of the substrate, and the results showed that the left kidney transporter expression showed no obvious change.…”

Section: Discussionmentioning

confidence: 99%

The System Profile of Renal Drug Transporters in Tubulointerstitial Fibrosis Model and Consequent Effect on Pharmacokinetics

et al. 2022

With the widespread clinical use of drug combinations, the incidence of drug–drug interactions (DDI) has significantly increased, accompanied by a variety of adverse reactions. Drug transporters play an important role in the development of DDI by affecting the elimination process of drugs in vivo, especially in the pathological state. Tubulointerstitial fibrosis (TIF) is an inevitable pathway in the progression of chronic kidney disease (CKD) to end-stage renal disease. Here, the dynamic expression changes of eleven drug transporters in TIF kidney have been systematically investigated. Among them, the mRNA expressions of Oat1, Oat2, Oct1, Oct2, Oatp4C1 and Mate1 were down-regulated, while Oat3, Mrp2, Mrp4, Mdr1-α, Bcrp were up-regulated. Pearson correlation analysis was used to analyze the correlation between transporters and Creatinine (Cr), OCT2 and MATE1 showed a strong negative correlation with Cr. In contrast, Mdr1-α exhibited a strong positive correlation with Cr. In addition, the pharmacokinetics of cimetidine, ganciclovir, and digoxin, which were the classical substrates for OCT2, MATE1 and P-glycoprotein (P-gp), respectively, have been studied. These results reveal that changes in serum creatinine can indicate changes in drug transporters in the kidney, and thus affect the pharmacokinetics of its substrates, providing useful information for clinical use.