Pharmacokinetic and bioequivalence study of endogenous compound tretinoin 10 mg capsules in healthy volunteers by base line correction approach

Thudi, Nageshwar Rao; Shrivastav, Vikesh Kumar; Monif, Tausif; Khuroo, Arshad; Gurule, Sanjay; Partani, Pankaj; Tandon, Monika; Mathur, Rajeev

doi:10.3109/10601333.2011.597762

Cited by 4 publications

(4 citation statements)

References 4 publications

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“…Predicted and observed mean plasma concentration-time profiles of atRA in healthy volunteers. (A) Administration of 10-mg atRA PO (as described in Thudi et al, 2011). (B) Administration of 20 mg atRA PO (as described in Peng et al, 2014).…”

Section: Resultsmentioning

confidence: 99%

“…In brief, the fraction absorbed (F a ) and a nominal flow in gut model (Q gut ) were predicted using atRA Caco-2 cell permeability data within Simcyp. The k a and lag time were estimated using the observed concentration-time profiles from three studies in healthy volunteers administered with a single oral dose of atRA (Ozpolat et al, 2003;Thudi et al, 2011;Peng et al, 2014). The reported concentration-time profiles were digitized using Plot Digitizer software (http://plotdigitizer.sourceforge.net), and one compartment pharmacokinetic model with first-order absorption was fitted to the data using Phoenix WinNonlin 6.4 (Pharsight Corporation, Cary, NC).…”

Section: Methodsmentioning

confidence: 99%

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Physiologically Based Pharmacokinetic Model of All-trans-Retinoic Acid with Application to Cancer Populations and Drug Interactions

Jing

Nelson

Paik

et al. 2017

J Pharmacol Exp Ther

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All- retinoic acid (RA) is a front-line treatment of acute promyelocytic leukemia (APL). Due to its activity in regulating the cell cycle, it has also been evaluated for the treatment of other cancers. However, the efficacy of RA has been limited byRA inducing its own metabolism during therapy, resulting in a decrease of RA exposure during continuous dosing. Frequent relapse occurs in patients receivingRA monotherapy. In an attempt to combat therapy resistance, inhibitors of RA metabolism have been developed. Of these, ketoconazole and liarozole have shown some benefits, but their usage is limited by side effects and low potency toward the cytochrome P450 26A1 isoform (CYP26A1), the mainRA hydroxylase. We determined the pharmacokinetic basis of therapy resistance to RA and tested whether the complex disposition kinetics ofRA could be predicted in healthy subjects and in cancer patients in the presence and absence of inhibitors of RA metabolism using physiologically based pharmacokinetic (PBPK) modeling. A PBPK model ofRA disposition was developed and verified in healthy individuals and in cancer patients. The population-based PBPK model of RA disposition incorporated saturable metabolic clearance ofRA, induction of CYP26A1 by RA, and the absorption and distribution kinetics ofRA. It accurately predicted the changes in RA exposure after continuous dosing and when coadministered with ketoconazole and liarozole. The developed model will be useful in interpretation ofRA disposition and efficacy, design of novel dosing strategies, and development of next-generation RA metabolism inhibitors.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Physiologically Based Pharmacokinetic Model of All-trans-Retinoic Acid with Application to Cancer Populations and Drug Interactions

Jing

Nelson

Paik

et al. 2017

J Pharmacol Exp Ther

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“…Some LFs were rejected because clinical trials included volunteers in the fed state, and/or it was not indicated whether the administered formulation was actually a lipidic one (Juvela N, tocopherol nicotinate; Selbex, teprenone; Accutane, isotretinoin; and Rapamune, sirolimus). If only one single valid study could be found, the LFs were not taken into account either (Depakene, valproic acid; Cipro, ciprofloxacin; Glakay capsules, menatetrenone; Vesanoid, tretinoin; Prometrium, progesterone; and Hectorol, doxercalciferol). The LFs of testosterone undecanoate (Andriol and Restandol) were discarded as well because the stability of this ester prodrug in the gastrointestinal tract remains unknown.…”

Section: Experimental Sectionmentioning

confidence: 99%

Linking in Vitro Lipolysis and Microsomal Metabolism for the Quantitative Prediction of Oral Bioavailability of BCS II Drugs Administered in Lipidic Formulations

et al. 2016

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Lipidic formulations (LFs) are increasingly utilized for the delivery of drugs that belong to class II of the Biopharmaceutics Classification System (BCS). The current work proposes, for the first time, the combination of in vitro lipolysis and microsomal metabolism studies for the quantitative prediction of human oral bioavailability of BCS II drugs administered in LFs. Marinol and Neoral were selected as model LFs, and their observed oral bioavailabilities (F) were obtained from published clinical studies in humans. Two separate lipolysis buffers, differing in the level of surfactant concentrations, were used for digestion of the LFs. The predicted fraction absorbed (F) was calculated by measuring the drug concentration in the micellar phase after completion of the lipolysis process. To determine first-pass metabolism (F·F), drug depletion studies with human microsomes were performed. Clearance values were determined by applying the "in vitro half-life" approach. The estimated F and F·F values were combined for the calculation of the predicted oral bioavailability (F). Results showed that there was a strong correlation between F and F values only when F was calculated using a buffer with surfactant concentrations closer to physiological conditions. The general accuracy of the predicted values suggests that the novel in vitro lipolysis/metabolism approach could quantitatively predict the oral bioavailability of lipophilic drugs administered in LFs.

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“…The differential ATRA sensitivity might be related to the CYP26 gene expression which was known to be involved in retinoic acid catabolism [4,5]. Although the pharmacokinetic parameters of ATRA in health volunteers have been described previously [6,7], no report has been performed for Chinese subjects.…”

Section: Introductionmentioning

confidence: 99%

Validation of a Liquid Chromatography-Electrospray Ionization-Tandem Mass Spectrometry Method for Determination of All-Trans Retinoic Acid in Human Plasma and Its Application to a Bioequivalence Study

et al. 2014

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A sensitive, reliable and specific LC-MS-MS method was developed and validated for the identification and quantitation of all-trans retinoic acid (ATRA) in human plasma. Acitretin was used as the internal standard (IS). After liquid-liquid extraction of 500 μL plasma with methyl tert-butyl ether (MTBE), ATRA and the IS were chromatographed on a HyPURITY C18 column (150 mm × 2.1 mm, 5 μm) with the column temperature set at 40 °C. The mobile phase was consisted of 40% phase A (MTBE-methanol-acetic acid, 50:50:0.5, v/v) and 60% phase B (water-methanol-acetic acid, 50:50:0.5, v/v) with a flow rate of 0.3 mL/min. The API 4000 triple quadrupole mass spectrometer was operated in multiple reaction monitoring (MRM) mode via the positive electrospray ionization interface using the transition m/z 301.4 → 123.1 for ATRA and m/z 326.9 → 177.1 for IS, respectively. The calibration curve was linear over the range of 0.45-217.00 ng/mL (r ≥ 0.999) with a lower limit of quantitation (LLOQ) of 0.45 ng/mL. The intra-and inter-day precisions values were below 8% relative standard deviation and the accuracy was from

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Pharmacokinetic and bioequivalence study of endogenous compound tretinoin 10 mg capsules in healthy volunteers by base line correction approach

Cited by 4 publications

References 4 publications

Physiologically Based Pharmacokinetic Model of All-trans-Retinoic Acid with Application to Cancer Populations and Drug Interactions

Physiologically Based Pharmacokinetic Model of All-trans-Retinoic Acid with Application to Cancer Populations and Drug Interactions

Linking in Vitro Lipolysis and Microsomal Metabolism for the Quantitative Prediction of Oral Bioavailability of BCS II Drugs Administered in Lipidic Formulations

Validation of a Liquid Chromatography-Electrospray Ionization-Tandem Mass Spectrometry Method for Determination of All-Trans Retinoic Acid in Human Plasma and Its Application to a Bioequivalence Study

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