Untitled

Wearley, Lorraine; Chien, Yie W.

doi:10.1023/a:1015827307516

Cited by 64 publications

(4 citation statements)

References 7 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This behavior for PD may result from the drug binding to skin, which is defined as a strong interaction of drug with skin tissue, compared to the partitioning. [33][34][35][36] It is known that binding to the skin induces a delay in drug permeation across the skin. [33][34][35][36] To prove this hypothesis, the time-course curve of cutaneous plasma concentration of PD was compared with the skin concentration (Fig.…”

Section: Nsaidsmentioning

confidence: 99%

Effect of Lipophilicity on in Vivo Iontophoretic Delivery. II. .BETA.-Blockers.

Tashiro

Sami

Shichibe

et al. 2001

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

Transdermal drug absorption includes several sequential processes, as follows: (1) drug absorption into the skin; (2) transfer from skin to cutaneous vein; (3) transport to systemic circulation by blood flow. In systemic therapy, it is necessary to transfer drug molecules from skin (application site) to cutaneous blood flow and to transport to the target organ through systemic circulation. [2][3][4][5][6][7] On the other hand, local therapy needs to accumulate drug molecules at the local site (skin, muscle and joint, etc.), but not to eliminate into the blood flow.2-7) Therefore, the evaluation of drug transfer properties into local blood flow would be expected to predict the systemic and local therapeutic effects.Previously, we have developed a method to investigate transdermal absorption processes in vivo, whereby the drug concentrations in skin, cutaneous vein and systemic vein are measured after iontophoretic delivery of drugs to rats. 8) Further, kinetic analysis of drug transfer from skin to cutaneous vein has been established by modifying a physiological pharmacokinetic model. 9) In the previous study, we investigated the effect of drug lipophilicity on the iontophoretic transdermal absorption of non-steroidal anti-inflammatory drugs (NSAIDs) such as salicylic acid, ketoprofen, naproxen and indomethacin.10) The transfer properties of these NSAIDs from skin to cutaneous vein decreased with an increase in their lipophilicity.The NSAIDs examined previously are acidic drugs with a carboxyl group. In the present study, b-blockers were selected as basic drugs having an amino group and included atenolol (AT), pindolol (PD), metoprolol (MP), acebutolol (AB), oxprenolol (OX) and propranolol (PP). The chemical structures and physicochemical properties are listed in Table 1. 11-13) These b-blockers are adequate for evaluating the effect of lipophilicity on transdermal absorption properties, because the molecular weights are of narrow range. As an indication of drug lipophilicity, we used the logarithm of n-octanol/buffer partition coefficient (Log P), which varied from Ϫ0.11 to 1.49 (pH 7.4, 37°C).12) The difference in the lipophilicity is a consequence of the difference in the aromatic substituents of the b-blockers.Beta-blockers are used in the treatment of hypertension, angina pectoris and cardiac arrhythmia.14) Because of their short elimination half-life (from several to less than 6 h), 15) sustained release formulations for oral administration have been developed to prolong the therapeutic effects.16-21) However, the oral absorption of b-blockers is influenced by hepatic first-pass metabolism. 15,22) Thus, the development of transdermal delivery systems may be expected to achieve good maintenance of optimal blood levels and the avoidance of first-pass effects. Anodal Iontophoresis Anodal iontophoresis was performed as described previously. 10) Briefly, male SpragueDawley rats (8-10 weeks old, Charles River Japan) were anesthetized with ether throughout the experiment, and their body temperature was maintained...

show abstract

Section: Nsaidsmentioning

confidence: 99%

Effect of Lipophilicity on in Vivo Iontophoretic Delivery. II. .BETA.-Blockers.

Tashiro

Sami

Shichibe

et al. 2001

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

show abstract

“…The in vitro transport of vasopressin and insulin across the excised hairless rat skin was studied by varying the different parameters of pulsed direct current and pH.I B~r n e t t e~~~ compared sodium ion flux resulting from pulsed of ~on~op~ores~s71,75,88,89, 172,204,[210][211][212][213]216,219,224,225,[229][230][231][232][233]242,243,247,[253][254][255][256] 606 SINGH AND SINGH constant current and voltage with the flux obtained from an equivalent continuous current using excised mouse skin. The pulsed iontophoretic sodium ion flux obtained without enhanced skin depolarization was shown to be equal to the flux obtained from an equivalent continuous current only at 10 KHz.…”

Section: In Vitro Studiesmentioning

confidence: 99%

Transdermal drug delivery by passive diffusion and iontophoresis: A review

Singh

1993

Medicinal Research Reviews

121

View full text Add to dashboard Cite

“…Extensive research is still required to elucidate more thoroughly the mechanisms of iontophoretic drug delivery [2], reversibility of skin permeability [54] and a skin model homologous of human skin [37].…”

Section: Future Perspectivesmentioning

confidence: 99%

Topical Iontophoretic Drug Delivery in vivo: Historical Development, Devices and Future Perspectives

Singh

Maibach

1993

Dermatology

View full text Add to dashboard Cite

Iontophoresis increases penetration of charged substances through the skin under a potential gradient. In spite of a century of publication, widespread use of the technique for enhancing percutaneous penetration has not yet been made. Knowledge of the mechanism and instrumentation increased exponentially in the last decade. In vivo iontophoretic devices vary in complexity from household current used in the past to a simple battery-and-rheostat type to modern electronic circuit devices. Extensive research is still required in the area of material science, electronics and skin toxicology to maximize this technique for controlled systemic transdermal administration of charged, hydrophilic and large drug molecules.

show abstract

Untitled

Cited by 64 publications

References 7 publications

Effect of Lipophilicity on in Vivo Iontophoretic Delivery. II. .BETA.-Blockers.

Effect of Lipophilicity on in Vivo Iontophoretic Delivery. II. .BETA.-Blockers.

Transdermal drug delivery by passive diffusion and iontophoresis: A review

Topical Iontophoretic Drug Delivery in vivo: Historical Development, Devices and Future Perspectives

Contact Info

Product

Resources

About