ABSTRACT
Transdermal drug delivery allows for a constant rate of drug administration and prolonged action, which can be beneficial to elderly patients who are often polymedicated. Several studies have compared dermatopharmacokinetics in the young and elderly with conflicting results. Despite the potential limitations of age-related changes in skin factors and cutaneous metabolism, marketed transdermal products generally do not report age-related differences in pharmacokinetics. This overview discusses the current data, summarizes marketed product findings and highlights the importance of further studies to evaluate age-related dermatopharmacokinetics.
Subject(s)
Drug Delivery Systems , Pharmaceutical Preparations/administration & dosage , Skin Absorption , Administration, Cutaneous , Age Factors , Aged , Aging , Humans , Permeability , Pharmaceutical Preparations/metabolism , Skin/metabolism , Transdermal PatchABSTRACT
Changes in the skin that occur in the elderly may put them at increased risk for altered percutaneous penetration from pharmacotherapy along with potential adverse effects. Skin factors that may have a role in age-related percutaneous penetration include blood flow, pH, skin thickness, hair and pore density, and the content and structure of proteins, glycosaminoglycans (GAGs), water, and lipids. Each factor is examined as a function of increasing age along with its potential impact on percutaneous penetration. Additionally, topical drugs that successfully overcome the barrier function of the skin can still fall victim to cutaneous metabolism, thereby producing metabolites that may have increased or decreased activity. This overview discusses the current data and highlights the importance of further studies to evaluate the impact of skin factors in age-related percutaneous penetration.
Subject(s)
Pharmaceutical Preparations/metabolism , Skin Absorption , Skin/metabolism , Administration, Cutaneous , Age Factors , Aged , Aging , Drug-Related Side Effects and Adverse Reactions , Humans , Hydrogen-Ion Concentration , Permeability , Pharmaceutical Preparations/administration & dosage , Skin/blood supplyABSTRACT
Age-related changes in branched chain fatty acid (BCFA) concentration were studied with the skin surface lipid from hairless mice. A large proportion of BCFA was present in the cholesterol ester (CE) and wax diester (WDE) fraction of the skin surface lipid from hairless mice. The concentration of iso-series BCFA was highest at infancy and decreased with advancing age in both CE and WDE fraction. The concentration of anteiso-series BCFA appeared to be constant throughout the experiment.
Subject(s)
Fatty Acids/analysis , Lipids/chemistry , Skin Physiological Phenomena , Skin/chemistry , Age Factors , Animals , Cholesterol Esters/chemistry , Fatty Acids/chemistry , Mice , Mice, Hairless , Phospholipids/chemistryABSTRACT
The present study was undertaken to identify the chemical structure of neutral lipid accumulated in cultured rat keratinocytes and to address their metabolism. Neutral lipid of similar mobility with alkyldiacylglycerol was isolated from cultured rat keratinocytes by thin layer chromatography. The long-chain diols derived from the neutral lipids were identified as 1-alkylglycerol based on the mass spectra of their nicotinylidene derivatives. Thus these neutral lipids were identified as 1-o-alkyl-2,3-diacylglycerols (ADAG). Addition of rat serum elevated the level of ADAG with increasing trend of linoleic acid concentration in this fraction. [14C]Acetate added to the confluent plates was incorporated into alkyl- and acyl-chains of ADAG with incubation in 24 h, and remained un-metabolized up to 72 h. This, however, is not the case for the label incorporation into phospholipid and triacylglycerol. Radioactivities of these two lipid fractions appeared to reach the maximum in 24 h, and thereafter decreased to 72 h with a similar decay curve. Incorporation of [14C]acetate into phospholipid and ADAG was significantly depressed, and that into triacylglycerol and free cholesterol was increased by the supplementation of the medium with rat serum. In concomitance with the accumulation of ADAG, the concentration of ethanolamine-plasmalogen increased in the cultured keratinocytes. The results of the present study first showed the elevated level of ether lipid synthesis in the proliferating primary culture of rat keratinocytes.
Subject(s)
Diglycerides/biosynthesis , Epidermis/metabolism , Glyceryl Ethers/metabolism , Keratinocytes/metabolism , Acetates/metabolism , Animals , Cells, Cultured , Culture Media , Epidermal Cells , Fatty Acids/analysis , Phospholipids/chemistry , Rats , Triglycerides/chemistryABSTRACT
A neutral lipid class was isolated by thin-layer chromatography from the skin surface lipids of the hairless mouse. The fraction migrated faster than triglycerides and had a migration rate similar to that of diacyl alkanediols (diester wax). Upon deacylation, however, the long-chain diols were identified as 1-alkylglycerol ethers based on their chromatographic properties and on the mass spectra of their nicotinylidene derivatives. Thus, the skin lipid fraction was identified as 1-O-alkyl-diacylglycerol. The alkyl moieties were all saturated and even-numbered and ranged in chainlength from C16 to C22 with 1-O-hexadecylglycerol amounting to 34% of the total glycerol ether moieties. The fatty acids derived from this lipid fraction were mostly monoenoic with chainlengths ranging from C16 to C24. The major acyl component was eicosenoic acid (20:1) representing 61% of the total fatty acids.
