| Title | Partitioning of Anti-inflammatory Steroid Drugs into Phosphatidylcholine and Phosphatidylcholine-Cholesterol Small Unilamellar Vesicles as Studied by Second-Derivative Spectrophotometry. | | Author(s) | Takegami S, Kitamura K, Funakoshi T, Kitade T | | Institution | Kyoto Pharmaceutical University. | | Source | Chem Pharm Bull (Tokyo) 2008 May; 56(5):663-7. | | Abstract | The partition coefficients (K(p)s) of six anti-inflammatory steroid drugs, dexamethasone (DMS), betamethasone (BMS), triamcinolone acetonide (TCLA), fluocinolone acetonide (FCLA), betamethasone 17,21-dipropionate (BMSDP), and clobetasole propionate (CBSP), for phosphatidylcholine (PC), and PC-cholesterol small unilamellar vesicles (SUVs) were determined by a second-derivative spectrophotometric method. The K(p) values were obtained with a relative standard deviation of below 10% and the following order was observed: BMS</=DMS<TCLA<FCLA<<BMSDP<CBSP. BMSDP which has a structure that the two hydroxyl groups of BMS are esterified with propionic acid showed a largely enhanced K(p) value of 10.5 times that of BMS. Further, replacement of a propionate group in BMSDP with a chlorine atom resulted in the highest K(p) value (CBSP) within the drugs examined, i.e., the K(p) value of CBSP was 1.2 times that of BMSDP. The presence of 30 mol% cholesterol in the SUV bilayers reduced these K(p) values to approximately 35-50% of those values for the PC SUVs, although the order of the K(p) values remained unchanged. The order of the K(p) values agreed with that of the reported dermatological therapeutic potency of these drugs, although the order of their log P values for n-octanol/water systems showed a discrepancy. Our results indicate that the potency of steroid drugs in dermatological treatments depends to some extent on the K(p) values of the drug, that is, the affinity of steroid drugs for PC bilayers influences their clinical potency, since potency is related to transdermal absorption. | | Language | eng | | Pub Type(s) | Journal Article
| | PubMed ID | 18451554 |
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