Recurrent methemoglobinemia due to enterohepatic recirculation of dapsone

2016 ◽  
Vol 258 ◽  
pp. S109-S110
Author(s):  
R.C. Tincu ◽  
C. Cobilinschi ◽  
D. Tomescu ◽  
Z. Ghiorghiu ◽  
R.A. Macovei
Pharmaceutics ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 778
Author(s):  
Bettina Gerner ◽  
Oliver Scherf-Clavel

Cabozantinib (CAB) is a receptor tyrosine kinase inhibitor approved for the treatment of several cancer types. Enterohepatic recirculation (EHC) of the substance is assumed but has not been further investigated yet. CAB is mainly metabolized via CYP3A4 and is susceptible for drug–drug interactions (DDI). The goal of this work was to develop a physiologically based pharmacokinetic (PBPK) model to investigate EHC, to simulate DDI with Rifampin and to simulate subjects with hepatic impairment. The model was established using PK-Sim® and six human clinical studies. The inclusion of an EHC process into the model led to the most accurate description of the pharmacokinetic behavior of CAB. The model was able to predict plasma concentrations with low bias and good precision. Ninety-seven percent of all simulated plasma concentrations fell within 2-fold of the corresponding concentration observed. Maximum plasma concentration (Cmax) and area under the curve (AUC) were predicted correctly (predicted/observed ratio of 0.9–1.2 for AUC and 0.8–1.1 for Cmax). DDI with Rifampin led to a reduction in predicted AUC by 77%. Several physiological parameters were adapted to simulate hepatic impairment correctly. This is the first CAB model used to simulate DDI with Rifampin and hepatic impairment including EHC, which can serve as a starting point for further simulations with regard to special populations.


Nanomedicine ◽  
2020 ◽  
Author(s):  
Gurinder Singh

Resveratrol (3,5,4′-trihydroxystilbene) is a polyphenolic compound existing in trees, peanuts and grapes and exhibits a broad spectrum of promising therapeutic activities, but it is unclear whether this entity targets the sites of action after oral administration. In vivo applicability of resveratrol has limited success so far, mainly due to its incompetent systemic delivery resulting from its low water solubility, poor bioavailability and short biological half-life. First-pass metabolism and presence of enterohepatic recirculation create doubt on the biological application of high doses typically used for in vitro trials. To augment bioavailability, absorption and uptake of resveratrol by cellular internalization, countless approaches have been implemented which involve the use of nanocarriers. Nanocarriers are a well-known delivery system used to reduce first-pass hepatic metabolism, overcome enterohepatic recirculation and accelerate the absorption of drugs via lymphatic pathways.


1998 ◽  
Vol 42 (12) ◽  
pp. 3136-3140 ◽  
Author(s):  
Saori Kojima ◽  
Masayuki Nadai ◽  
Kiyoyuki Kitaichi ◽  
Li Wang ◽  
Toshitaka Nabeshima ◽  
...  

ABSTRACT There is evidence indicating that the carbapenem antibiotic panipenem decreases plasma concentrations of valproic acid (VPA) in epileptic patients during VPA therapy. The mechanism for panipenem-induced changes in the pharmacokinetics of VPA was investigated in rats with and without bile duct cannulation. The effect of panipenem on the pharmacokinetics of diclofenac, which undergoes extensive enterohepatic recirculation, was also examined. VPA (50 mg/kg of body weight) or diclofenac (10 mg/kg of body weight) was administered intravenously under the steady-state plasma panipenem concentration of 4 μg/ml, which had been achieved by a constant infusion rate. Panipenem decreased the plasma VPA concentrations in rats without bile duct cannulation but did not change the volume of the initial space and protein binding of VPA. However, panipenem had no effect on the plasma VPA concentrations and the biliary excretion of VPA in rats with bile duct cannulation. The secondary increase in plasma diclofenac concentration observed in the absence of panipenem was diminished in the presence of panipenem. These findings suggest that panipenem decreases plasma VPA concentrations by suppressing its enterohepatic recirculation, probably due to a panipenem-induced decrease in the numbers of enteric bacteria.


2020 ◽  
Vol 158 (6) ◽  
pp. S-1220
Author(s):  
Victoria M. Gershuni ◽  
Elliot S. Friedman ◽  
Sayaka A. Ogawa ◽  
Dillon Murphy ◽  
Lillian Chau ◽  
...  

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