Role of physical chemical properties in drug relay into skin compartments.
The ability of a drug to reach the interstitial fluid is an important aspect of drug efficacy - as a possible indicator of skin and cell compartment concentration. This overview addresses the relationship of the physical properties of several antibiotics to their ability to enter the interstitial fluid utilizing a cantharidin blister model. By collecting pharmacokinetic data for 12 antibiotics administered orally and 11 intravenously, we compared the fraction of drug that reaches the interstitial fluid (AUC(blister)/AUC(serum)) to partition coefficients. Following data analysis, we found no correlation (p = 0.98 and 0.09, respectively) between hydrophobicity and the ability to reach the interstitium. Both orally and intravenously administered antibiotics display a strong linear correlation (p < 0.001 and p = 0.006, respectively) in the total concentration found in the serum and interstitial fluid indicating that serum concentration may be an important factor in dictating interstitial fluid concentration. This correlation may prove useful in clinical application as a means of determining interstitial fluid concentration by measuring only serum levels.
Fortenbach
C R
CR
Department of Dermatology, School of Medicine, University of California, San Francisco, California 94143-0989, USA. cfortenbach@ucdavis.edu
Modjtahedi
B S
BS
Maibach
H I
HI
D000284:Administration, Oral; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001768:Blister / Q000378:metabolism; D002193:Cantharidin / Q000633:toxicity; D045604:Extracellular Fluid / Q000378:metabolism*; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007275:Injections, Intravenous; D008954:Models, Biological; D014018:Tissue Distribution
D000900:Anti-Bacterial Agents; D002193:Cantharidin