| 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 |
Notes:
- CRABP: cellular retinoic acid binding protein.
- RA: retinoic acid.
- RAR: retinoic acid receptor.
- RXR: retinoid X receptor.
Reference:
Bolognia Dermatology 2nd edition