Lecture Notes: The key pharmacologic features and nuclear binding profile of retinoids

Retinoid Type Systemic absorption (% dose): Elimination half-life Metabolism Excretion Nuclear receptor and binding protein profile
Topical retinoids
Low (Limited propensity for distribution to systemic tissues)

Tretinoin Natural (1st generation) <2% in normal skin Normally present in the skin Isomerization to 13-cis-RA (epidermis) Desquamation, hepatobiliary RAR; CRABP; no RXR
9-cis-retinoic acid (alitretinoin) Natural (2nd generation) Minimal Normally present in the skin Main metabolite: 4-oxo-9-cis-RA Desquamation, hepatobiliary RXR and RAR
Adapalene 3rd generation Minimal Unknown Minimal biotransformation due to chemical rigidity Desquamation, hepatobiliary RAR-b, -g > -a; no RXR
Tazarotene 3rd generation <1–6% in normal skin 16 hours (tazarotenic acid) Rapid skin ester hydrolysis to form its active metabolite, tazarotenic acid (within 20 min); excreted metabolites: sulfoxides, sulfones Desquamation, urine (within 3 days), feces (within 7 days) RAR-b, -g > -a; no RXR
Systemic retinoids
Bioavailability (Increased with food intake, highly variable)

Tretinoin Natural (1st generation) 50% 1 hour Hepatic; main metabolites: cis- and trans-4-oxo derivatives Biliary, renal RAR; CRABP; no RXR (9-cis binds both RXR and RAR)
Isotretinoin (13-cis-RA) Natural (1st generation) 25% 20 hours Hepatic, endogeneous concentration reached within 2 weeks; main metabolite: 4-oxo-isotretinoin Biliary, renal No clearly identified affinity for any retinoid receptor.
Etretinate 2nd generation 40% 120 days Hepatic, hydrolysis to acitretin Biliary, renal (accumulation in fat) No clearly identified affinity for any retinoid receptor.
Acitretin 2nd generation 60% 2 days Hepatic, re-esterification to etretinate indirectly increased by alcohol consumption; main metabolite: cis-acitretin Biliary, renal No clearly identified affinity for any retinoid receptor.
Bexarotene 3rd generation Unknown 7–9 hours Hepatic Hepatobiliary RXR

  • CRABP: cellular retinoic acid binding protein.
  • RA: retinoic acid.
  • RAR: retinoic acid receptor.
  • RXR: retinoid X receptor.

Bolognia Dermatology 2nd edition 

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