The metabolism and pharmacokinetics of isotretinoin in patients with acne and rosacea are not influenced by ethanol

Larsen, Finn Breinholt; Jakobsen, Preben; Larsen, Christian Grónhøj; Heidenheim, Michael; Held, Elisabeth; Nielsen‐Kudsk, F.

doi:10.1111/j.1365-2133.2009.09241.x

Cited by 10 publications

(5 citation statements)

References 15 publications

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“…This caveat is not described in the abstract, which may lead to misinterpretation by casual readers. Similarly, there is a lot of discussion of potential long‐term risks of suicide with isotretinoin exposure, but this is not consistent with the pharmacokinetics of isotretinoin 14 . Thus, the increase in all suicide attempts for female patients 11 years after treatment, with an SIR of 1·36 (95% CI 1·06–1·70) is not consistent with a temporal relationship with drug exposure and is much more likely to be endogenous.…”

Section: Commentmentioning

confidence: 98%

Acne, isotretinoin and suicide attempts: a critical appraisal

Langan

Batchelor

2011

British Journal of Dermatology

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Sundström et al. (BMJ 2010; 341: c5812) conclude that there was an increased risk of suicide attempts up to 6 months after the end of treatment with isotretinoin and advise close monitoring for up to a year after completing a course of treatment. Patients with a history of suicide attempts before treatment made fewer new attempts at suicide than those where suicidality was observed in connection with treatment, suggesting that patients with severe acne with a history of attempted suicide should not automatically be refused isotretinoin treatment. The authors also state that suicide risk was already rising prior to treatment and that the additional risk cannot therefore be attributed to isotretinoin use.

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Section: Commentmentioning

confidence: 98%

Acne, isotretinoin and suicide attempts: a critical appraisal

Langan

Batchelor

2011

British Journal of Dermatology

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“…According to the metabolic pathway of 13- cis -RA ( Figure S1 ), it was metabolized by liver enzymes (CYP2C8, CYP2C9, CYP3A4 and CYP2B6) and converted to all- trans -retinoic acid (all- trans -RA), 4-oxo-13- cis -retinoic acid (4-oxo-13- cis -RA) and 4-oxo-all- trans -retinoic acid (4-oxo-all- trans -RA). Approximately 20%–30% of 13- cis -RA can convert to all- trans -RA [ 2 , 3 ]. 4-oxo-13- cis -RA and 4-oxo-all- trans -RA are seldom converted between each other in plasma [ 2 , 4 ].…”

Section: Introductionmentioning

confidence: 99%

“…Approximately 20%–30% of 13- cis -RA can convert to all- trans -RA [ 2 , 3 ]. 4-oxo-13- cis -RA and 4-oxo-all- trans -RA are seldom converted between each other in plasma [ 2 , 4 ]. All- trans -RA can bind with the retinoic acid receptor on epidermal cells to stimulate the differentiation of keratinocytes, decrease the cohesion between keratinocytes and then make keratinocytes normalize [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

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Determination of 13-cis-Retinoic Acid and Its Metabolites in Plasma by Micellar Electrokinetic Chromatography Using Cyclodextrin-Assisted Sweeping for Sample Preconcentration

et al. 2021

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The online preconcentration technique, cyclodextrin-assisted sweeping (CD-sweeping), coupled with micellar electrokinetic chromatography (MEKC) was established to determine 13-cis-retinoic acid (13-cis-RA), all-trans-retinoic acid (all-trans-RA) and 4-oxo-13-cis-retinoic acid (4-oxo-13-cis-RA) in human plasma. A CD-sweeping buffer (45 mM borate (pH 9.2), containing 80 mM sodium dodecyl sulfate (SDS) and 22 mM hydroxypropyl β-CD (HP-β-CD) was introduced into the capillary and, then, the sample dissolved in 70 mM borate (pH 9.2): methanol = 9:1 (v/v) was injected into capillary by pressure. The separation voltage was 23 kV. Compared to the conventional cyclodextrin-micellar electrokinetic chromatography (CD-MEKC) method, the new technique achieved 224–257-fold sensitivity enrichment of analytes. The limits of detection of 13-cis-RA, all-trans-RA were 1 ng/mL, whereas that of 4-oxo-13-cis-RA was 25 ng/mL in plasma. The linear ranges of 13-cis-RA, all-trans-RA were between 15 and 1000 ng/mL, whereas that of 4-oxo-13-cis-RA was between 75 and 1500 ng/mL. The coefficient of correlation between the concentration of analytes and peak area ratio of analytes and internal standard (2, 4-dihydroxy-benzophenone) for intra-day (n = 3) and inter-day (n = 5) analyses were both greater than 0.999. The optimized experimental conditions were successfully applied to determine 13-cis-retinoic acid and its metabolites in plasma samples from a patient during the administration of 13-cis-RA for treating acne.

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“…In patients with hepatic dysfunction, like Gilbert's syndrome, we would expect an increased sensitivity to isotretinoin that is metabolised by hepatic oxidation and biliary excretion 6 7…”

Section: Introductionmentioning

confidence: 99%

Hepatotoxicity of isotretinoin in patients with acne and Gilbert's syndrome: a comparative study

et al. 2014

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ObjectivesThe objective of our follow-up study is to evaluate liver function tests (LFTs) and lipid profiles in patients with Gilbert's syndrome treated with isotretinoin because of severe acne.SettingDermatology outpatient clinics of three regional hospitals of Jaén (Spain).ParticipantsOver 4 years, we included all patients diagnosed with severe acne. Only 37 patients were identified, of which 11 had Gilbert's syndrome.InterventionsAll patients were treated with isotretinoin and followed-up in our outpatient clinics after 10 and 20 weeks. Patients were subjected to an interview questionnaire which included data on age, gender, complete blood count, coagulation profile, fasting blood glucose, LFTs and lipid profiles. Data and results of patients with severe acne and Gilbert's syndrome were compared with those of 26 patients with only severe acne (control group).Primary outcomeBlood analyses were repeated in the follow-up visits.ResultsIn patients with Gilbert's syndrome, bilirubin levels showed substantial decrease over the 20-week follow-up, with more decrease after 10 weeks. None of the control group patients had significant increase in total bilirubin levels after 10 and 20 weeks of follow-up. Liver enzymes were maintained within normal levels in both groups. Both study groups did not show significant pathological increase in lipid profile levels. LDL levels were increased in the two study groups, but this increase was less substantial in patients with Gilbert's syndrome.ConclusionsOur preliminary results suggest that oral isotretinoin could be an effective, safe treatment for patients with Gilbert's syndrome, and may lower bilirubin levels in the first 10 weeks of treatment. Limitations of the study include the small numbers of participants and the fact that it is restricted to one region of Spain.

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The metabolism and pharmacokinetics of isotretinoin in patients with acne and rosacea are not influenced by ethanol

Cited by 10 publications

References 15 publications

Acne, isotretinoin and suicide attempts: a critical appraisal

Acne, isotretinoin and suicide attempts: a critical appraisal

Determination of 13-cis-Retinoic Acid and Its Metabolites in Plasma by Micellar Electrokinetic Chromatography Using Cyclodextrin-Assisted Sweeping for Sample Preconcentration

Hepatotoxicity of isotretinoin in patients with acne and Gilbert's syndrome: a comparative study

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