Determination of isotretinoin in human plasma: Application to pharmacokinetic study

Abo-Talib, Nisreen F.; Tammam, Marwa Hosny; Hassan, Essam E.

doi:10.1016/j.bfopcu.2012.09.001

Cited by 5 publications

(5 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It was reported that isotretinoin suppresses proliferation of SZ95 sebocytes at day 7 and 14 with concentrations (0.1-0.001 µM) achievable in serum [42][43][44] and at higher levels (10 and 1 µM) [12,21,45,46]. Also, in another cell line (SEB-1 sebocytes) 0.1, 0.5, and 1 µM isotretinoin reduced cellular proliferation and activated apoptosis after 48 and 72 hours.…”

Section: Discussionmentioning

confidence: 99%

Effects of Isotretinoin on the Phosphoinositide-3-kinase/Akt/FoxO1 Pathway and Molecular Functions of SZ95 Sebocytes In vitro

Mirdamadi¹,

Thielitz²,

Wiede³

et al. 2017

J Clin Exp Dermatol Res

View full text Add to dashboard Cite

Objective: For more than 3 decades, isotretinoin [13-cis retinoic acid (13-cis RA)] is established as the most potent oral treatment for severe acne. However, the molecular mechanisms of isotretinoin action have not been fully elucidated. Recently, we showed that insulin and insulin-like growth factor 1 (IGF-1) increase differentiation and decrease proliferation of SZ95 sebocytes in vitro via activation of the phosphoinositide 3-kinase (PI3K)/Akt/forkhead box-O1 (FoxO1) pathway. Furthermore, this pathway is activated in patient acne biopsies in vivo. Using SZ95 sebocytes as an in vitro model, the aim of this study was to investigate the effect of isotretinoin on PI3K pathway activation. Methods: SZ95 sebocytes were treated under light protection with 0.1 µM isotretinoin in the presence or absence of 1.0 and 0.1 µM IGF-1 or insulin or 50 µM LY294002 inhibitor in a time-dependent manner. The expression of p-Akt and its downstream target p-FoxO1 was analyzed by Western blot. FoxO transcriptional activity was measured by dual luciferase assay. Nuclear and cytoplasmic mobilization of FoxO1, p-FoxO1, Akt, and p-Akt were also determined by immunofluorescence microscopy. Proliferation of sebocytes was measured by [ 3 H]-thymidine incorporation and sebocyte differentiation by oil red O staining. Results: We show that isotretinoin activates the PI3K/Akt pathway and decreases the nuclear content of FoxO1 and its transcriptional activity in sebocytes in vitro and in sebaceous gland biopsies from an isotretinoin-treated acne patient. Isotretinoin reduces the proliferation of IGF-1-or insulin-stimulated sebocytes more effectively than IGF-1 and insulin alone. However, it normalizes the increased lipid accumulation in IGF-1-or insulin-stimulated sebocytes via a PI3K-independent pathway. Conclusion: Our data from the SZ95 sebocyte in vitro model suggest that the potent therapeutic effect of isotretinoin in acne is not mediated via the PI3K/Akt/FoxO1 pathway.

show abstract

Section: Discussionmentioning

confidence: 99%

Effects of Isotretinoin on the Phosphoinositide-3-kinase/Akt/FoxO1 Pathway and Molecular Functions of SZ95 Sebocytes In vitro

Mirdamadi¹,

Thielitz²,

Wiede³

et al. 2017

J Clin Exp Dermatol Res

View full text Add to dashboard Cite

show abstract

“…200 µl plasma was pipetted into a 2 ml polypropylene tube and acetonitrile (1.5ml) was added. The mixture was vortex mixed briefly, and after standing for 30s at room temperature, the mixture was centrifuged at 3500rpm for 10min and the supernatant (20μL) was injected into HPLC system.The calibration curve was constructed over a range of 1.0-250 ng/ml in plasma (R 2 = 0.9947) [13]. Pharmacokinetic parameters C max , T max and AUC were calculated using PK Solver Software [14].…”

Section: Solubility Studymentioning

confidence: 99%

Enhanced Oral Bioavailability of Alitretinoin by Lipid Drug Delivery System

Bhasin¹,

Patel²

2015

Pharm Anal Acta

View full text Add to dashboard Cite

Alitretinoin is an endogenous retinoid and acts as a pan-agonist at retinoid receptors, binding with high affinity to both retinoic acid receptors and retinoid X receptors. Oral alitretinoin once daily is approved for use in patients with severe chronic hand eczema unresponsive to treatment with potent topical corticosteroids. The bioavailability of alitretinoin after oral admin istration is low and subject to large inter-individual variation. The purpose of this study was to evaluate the relationship of solubility and dissolution profiles of alitretinoin in vitro and their impact on the oral bioavailability of alitretinoin in rats. The work plan involves using simple and widely used practices under small scale pharmaceutical industry setups in India. The solubility of alitretinoin in vehicles of varying Hydrophilic lipophilic balance (HLB) values was determined and selected components were used to formulate different compositions for in vitro drug release dissolutions studies. The prototypes composition of soybean oil and stearoyl macrogol-32 glycerides provided a stable and maximum drug releasing product. The pharmacokinetic study in rats for the optimized formulation was performed and compared against innovator composition. Lipid formulation system of alitretinoin had significantly increased the peak serum concentration (C max), area under the curve (AUC) and reduction was observed in time to reach peak serum concentration (T max) compared to marketed formulation. The data although reaffirms established correlations between dissolution and bioavailability, it interestingly points towards a complex relationship exist between HLB and thermodynamic activity profile of drug in vehicles in affecting alitretinoin's solubility, dissolution and bioavailability.

show abstract

“…After the 40 mg oral administration of Isotretinoin to fasting healthy volunteers, the maximum plasma concentrations reported ranged from 167-459 ng/ mL, reached in 3.2 h [2]; same dose in acne patients caused maximum plasma concentrations ranging from 98-535 ng/mL (average 262 ng/ mL) in 2-9 h average [3]. Isotretinoin bioavailability increases from 1½ to 2 times more, when ingested with food.…”

Section: Introductionmentioning

confidence: 97%

“…One of the main metabolites, 4-oxo-isotritenoine, is present in maximum plasma concentrations after 6 h of a single dose, remaining constant after 7 days Isotretionion's elimination half-life is 7-37 h. The medicine binds to plasma proteins, almost exclusively to albumin (99.9%). Another characteristic of this drug is that it crosses the placental barrier [2,3]. The elimination halflife on healthy subjects after a 40 mg dose ranges from 10-20 h, being up to 90 h on patients who reach stationary states.…”

Section: Introductionmentioning

confidence: 99%

“…Epidermic concentration is very low, and has not been found a progressive accumulation in serum, epidermic or subcutaneous cell tissue. Once treatment is discontinued, Isotretinoin disappears from serum and skin in 2-4 weeks [2,3]. According to FDA and EMA, two products that contain the same active principle are bioequivalent if they meet the conditions above [4,5].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Bioequivalence Study of Two Formulations That Contain Isotretinoin 20 mg Capsules in Healthy Colombian Volunteers

Vargas¹,

Villarraga²,

Batista³

et al. 2016

J Bioequiv Availab

View full text Add to dashboard Cite

Determination of isotretinoin in human plasma: Application to pharmacokinetic study

Cited by 5 publications

References 19 publications

Effects of Isotretinoin on the Phosphoinositide-3-kinase/Akt/FoxO1 Pathway and Molecular Functions of SZ95 Sebocytes In vitro

Effects of Isotretinoin on the Phosphoinositide-3-kinase/Akt/FoxO1 Pathway and Molecular Functions of SZ95 Sebocytes In vitro

Enhanced Oral Bioavailability of Alitretinoin by Lipid Drug Delivery System

Bioequivalence Study of Two Formulations That Contain Isotretinoin 20 mg Capsules in Healthy Colombian Volunteers

Contact Info

Product

Resources

About