Circadian variation of mycophenolate mofetil pharmacokinetics in rats

Dridi, Ichrak; Ben-Cherif, Wafa; Aouam, Karim; Ben‐Attia, Mossadok; Klouz, Anis; Reinberg, A; Boughattas, Naceur A.

doi:10.1016/j.ejps.2014.02.015

Cited by 17 publications

(9 citation statements)

References 31 publications

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“…Circadian variations may also be one of the factors influencing MMF variability. In a study on rats, it was shown that MPA C max , AUC from 0 to 24 h (AUC 0-24 ) and plasma clearance varied significantly according to the circadian dosing-time (Dridi et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Monitoring of mycophenolate mofetil metabolites in children with nephrotic syndrome and the proposed novel target values of pharmacokinetic parameters

Sobiak

Resztak

Ostalska‐Nowicka

et al. 2015

European Journal of Pharmaceutical Sciences

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Section: Introductionmentioning

confidence: 99%

Monitoring of mycophenolate mofetil metabolites in children with nephrotic syndrome and the proposed novel target values of pharmacokinetic parameters

Sobiak

Resztak

Ostalska‐Nowicka

et al. 2015

European Journal of Pharmaceutical Sciences

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“…Circadian rhythms have been observed for bile flow, biliary concentrations, and excretory rates of biliary lipids, which exhibited a peak at ZT 16 and a trough at ZT 4 in rats (Nakano, Tietz, & LaRusso, 1990). Examples of efflux substrates for which biliary excretion is a relevant elimination route include the 7‐ O ‐glucuronide metabolite of mycophenolic acid (Dridi et al, 2014) and irinotecan (Filipski et al, 2014). Interestingly, the second peak of mycophenolic acid in plasma, corresponding to its enterohepatic circulation, always occurred 6 hr after administration, independently of the time of administration and in spite of its glucuronide being an MRP2 substrate (Dridi et al, 2014).…”

Section: Chronopharmacokinetics: Non‐clinical Datamentioning

confidence: 99%

“…Examples of efflux substrates for which biliary excretion is a relevant elimination route include the 7‐ O ‐glucuronide metabolite of mycophenolic acid (Dridi et al, 2014) and irinotecan (Filipski et al, 2014). Interestingly, the second peak of mycophenolic acid in plasma, corresponding to its enterohepatic circulation, always occurred 6 hr after administration, independently of the time of administration and in spite of its glucuronide being an MRP2 substrate (Dridi et al, 2014). Meanwhile, P‐gp is essential for the detoxification of irinotecan, which demonstrated better tolerability during the rest phase of mice, when the residence time of the main cytotoxic metabolite was shortest (Filipski et al, 2014).…”

Section: Chronopharmacokinetics: Non‐clinical Datamentioning

confidence: 99%

“…Rhythmic oscillations have been described for plasma protein levels of albumin and α1‐acid glycoprotein in rodents, with acrophases at ZT 2 (albumin) and ZT 19/ZT 1 (α1‐acid glycoprotein; Scheving, Pauly, & Tsai, 1968). Such fluctuations are particularly critical for drugs with high binding to plasma proteins (>90%) and small volume of distribution ( V d ; Dridi et al, 2014). In Table 2, three highly bound drugs exhibited significantly higher V d during the rest phase: roscovitine (ZT 3), mycophenolic acid (ZT 1), and valproic acid (ZT 7), the exception being erlotinib (ZT 13: early activity phase).…”

Section: Chronopharmacokinetics: Non‐clinical Datamentioning

confidence: 99%

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Timing in drug absorption and disposition: The past, present, and future of chronopharmacokinetics

Bicker

Alves

Falcão

2020

British J Pharmacology

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The importance of drug dosing time in pharmacokinetics, pharmacodynamics, and toxicity is receiving increasing attention from the scientific community. In spite of mounting evidence that circadian oscillations affect drug absorption, distribution, metabolism, and excretion (ADME), there remain many unanswered questions in this field and, occasionally, conflicting experimental results. Such data arise not only from translational difficulties caused by interspecies differences but also from variability in study design and a lack of understanding of how the circadian clock affects physiological factors that strongly influence ADME, namely, the expression and activity of drug transporters. Hence, the main goal of this review is to provide an updated analysis of the role of the circadian rhythm in drug absorption, distribution across bloodtissue barriers, metabolism in hepatic and extra-hepatic tissues, and hepatobiliary and renal excretion. It is expected that the research suggestions proposed here will contribute to a tissue-targeted and time-targeted pharmacotherapy.

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“…Due to the affinity of rats MRP2 to MPAG being around 3.6 times more than human MRP2, MPAG is majorly excreted into the urine in humans and majorly excreted into bile in rats [30]. There were several pre-clinical PK studies of MPA in healthy rats [31][32][33] and Nagase analbuminemic rats [34].…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetic Model Analysis of Supralingual, Oral and Intravenous Deliveries of Mycophenolic Acid

Gao

Tsai

et al. 2021

Pharmaceutics

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Mycophenolic acid (MPA) is commonly used for organ rejection prophylaxis via oral administration in the clinic. Recent studies have shown that MPA also has anticancer activities. To explore new therapeutic options for oral precancerous/cancerous lesions, MPA was designed to release topically on the dorsal tongue surface via a mucoadhesive patch. The objective of this study was to establish the pharmacokinetic (PK) and tongue tissue distribution of mucoadhesive MPA patch formulation after supralingual administration in rats and also compare the PK differences between oral, intravenous, and supralingual administration of MPA. Blood samples were collected from Sprague Dawley rats before and after a single intravenous bolus injection, a single oral dose, or a mucoadhesive patch administration on the dorsal tongue surface for 4 h, all with a dose of 0.5 mg/kg of MPA. Plots of MPA plasma concentration versus time were obtained. As multiple peaks were found in all three curves, the enterohepatic recycling (EHR) model in the Phoenix software was adapted to describe their PK parameters with an individual PK analysis method. The mean half-lives of intravenous and oral administrations were 10.5 h and 7.4 h, respectively. The estimated bioavailability after oral and supralingual administration was 72.4% and 7.6%, respectively. There was a 0.5 h lag-time presented after supralingual administration. The results suggest that the systemic plasma MPA concentrations were much lower in rats receiving supralingual administration compared to those receiving doses from the other two routes, and the amount of MPA accumulated in the tongue after patch application showed a sustained drug release pattern. Studies on the dynamic of drug retention in the tongue after supralingual administration showed that ~3.8% of the dose was accumulated inside of tongue right after the patch removal, ~0.11% of the dose remained after 20 h, and ~20.6% of MPA was not released from the patches 4 h after application. The data demonstrate that supralingual application of an MPA patch can deliver a high amount of drug at the site of administration with little systemic circulation exposure, hence lowering the potential gastrointestinal side effects associated with oral administration. Thus, supralingual administration is a potential alternative route for treating oral lesions.

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Circadian variation of mycophenolate mofetil pharmacokinetics in rats

Cited by 17 publications

References 31 publications

Monitoring of mycophenolate mofetil metabolites in children with nephrotic syndrome and the proposed novel target values of pharmacokinetic parameters

Monitoring of mycophenolate mofetil metabolites in children with nephrotic syndrome and the proposed novel target values of pharmacokinetic parameters

Timing in drug absorption and disposition: The past, present, and future of chronopharmacokinetics

Pharmacokinetic Model Analysis of Supralingual, Oral and Intravenous Deliveries of Mycophenolic Acid

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