Changes in Digoxin Pharmacokinetics Treated with Lipopolysaccharide in Wistar Rats

Changes of midazolam pharmacokinetics in Wistar rats treated with lipopolysaccharide: relationship between total CYP and CYP3A2

“…this study were consistent with published data. 9,15 On the other hand, hepatic total CYP contents were significantly decreased on day 1, and remained significantly low until day 3 (Fig. 2).…”

“…In this study, plasma TNF-α, IL-1β, and NOx concentrations and total CYP, CYP3A2, and CYP2C11 contents in 294 Kato, Yamashita, Moriguchi et al the liver were measured using a transient LPS-induced endotoxemia model of rats that were able to recover. 8,9 The plasma TNF-α, IL-1β, and NOx concentrations in the LPS (+) group were significantly higher than those in the control groups. Time to reach maximum concentration values were 3 h for TNF-α, 6 h for IL-1β, and 12 h or longer for NOx, indicating that plasma TNF-α concentrations were increased earlier than IL-1β and NOx after LPS administration, and then decreased to preadministration levels within 48 h after LPS administration (data not shown).…”

“…[5][6][7] However, there are few reports about the recovery process on drug pharmacokinetics during infection. [8][9][10] In this study, we investigated the effects of LPS on total cytochrome P450 (CYP), CYP3A2, and CYP2C11 contents in the liver, and measured tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and nitrite/nitrate (NOx) concentrations in plasma in a transient LPS-induced endotoxemia model of rats that were able to recover. 8 In addition, to assess the effects of LPS on CYP3A2 activities, the pharmacokinetics of midazolam, 11,12 a CYP3A2 substrate, were investigated.…”

Inflammation Induces Changes in the Functional Expression of P-gp, BCRP, and MRP2: An Overview of Different Models and Consequences for Drug Disposition

“…The functionality of transporters also represents crucial information which is not clearly elucidated and that represents the final step in the investigations on drug transporter modulations. Some reports on treated rodents have shown important modifications in the pharmacokinetics of several drugs during inflammation including digoxin, ciclosporin A, fexofenadine, acebutolol, doxorubicin, verapamil, and propranolol [ 117 , 125 , 126 , 131 ]. Nevertheless, further studies are required to better identify pharmacokinetic changes due to the modulation of ABC transporters.…”

IL-1 receptor blockade alleviates endotoxin-mediated impairment of renal drug excretory functions in rats

“…Consequent ischemia of tubular segments leads to an alteration of transport functions, with reduced urinary concentration ability and eventually to acute tubular necrosis. The urinary excretion of endo-and xenobiotics is further mitigated by profound changes in the expression of transporting proteins in tubules (2,5,18,26,27). In this situation, the pharmacological modulation of the regulatory mediator pathways, such as the inhibition of iNOS or activation of the protective heme oxygenase (HMOX)-CO pathway, may significantly restore GFR and tubular excretory functions (20,35) and consequently affect the pharmacokinetics of drugs administered in therapy for sepsis (55).…”