Pharmacokinetics transdermal delivery

Hadgraft J. Recent developments in topical and transdermal delivery. Eur J Drug Metabol Pharmacokinet 1996 21 165-173. 

A. Wiegand, K. Bauer, R. Bonn, et al. Pharmacodynamic and pharmacokinetic evaluation of a new transdermal delivery system with a time-dependent release of glyceryl trinitrate. J. Clin. Pharmacol. 32 77—84, 1992. 

T. Loftsson and N. Bodor, The pharmacokinetics and transdermal delivery of loteprednol etabonate and related soft steroids, Adv. Drug Del. Rev. 14 293 (1994). 

Berner, B. John, V.A. Pharmacokinetic characterization of transdermal delivery systems. Clin. Pharmacokinet. 1994, 26, 121-134. 

Holley, F.O. van Steennis, C. Postoperative analgesia with fentanyl pharmacokinetics and pharmacodynamics of constant-rate IV and transdermal delivery. Br. J. Anaesthesia. 1988, 60, 608-613. 

T. Loftsson and N. Bodor, The pharmacokinetics and transdermal delivery of loteprednol etabonate and related soft steroids, Adv. Drug Del. Rev. 14 293 (1994). N. Bodor, T. Murakami, and W.-M. Wu, Soft drugs. 18. Oral and rectal delivery of loteprednol etabonate, a novel soft corticosteroid, in rats-for safer treatment of gastrointestinal inflammation, Pharm. Res. 72 869 (1995). 

Figure 9.2 Pharmacokinetic profiles of diclofenac in rats after transdermal administration of Voltaren Emulgel and microemulsion compared to subcutaneous administration. The microemulsion formulation was superior to Voltaren Emulgel with respect to transdermal delivery and acted for longer time as compared to subcutaneous injection. (Figure redrawn with data from Ref. [59], reprinted with permission of Elsevier.)...

Roy, S.D. Manoukian, E. Transdermal delivery of ketorolac tromethamine Permeation enhancement, device design, and pharmacokinetics in healthy humans. J.Pharm.Sci., 1995, 84, 1190-1196... 

Within the last 10, years several new compounds were launched in the field of non-steroidal antiinflammatory drugs (NSAIDs) with a clear focus on cyclooxygenase type 2 selective compounds. In the field of opioids on the other hand no new drugs have passed phase III clinical trials. In this field innovation has been achieved through new pharmaceutical formulations of known drugs such as transdermal systems, e.g. buprenorphine patch, transmucosal systems, e.g. fentanyl lollipop, or rectal delivery systems containing e.g. morphine. These were developed in order to reduce opioid side effects, but also to overcome pharmacokinetical limitations, in particular to prolong compliance and duration of action. 

Moore L, Chien WY. Transdermal drug delivery a review of pharmaceutics, pharmacokinetics, and pharmacodynamics. Crit. Rev. Ther. Drug Carrier Sys. 1988 4 285-349. 

Cevc, G. Transdermal drug delivery of insulin with ultra-deformable carriers. Clin. Pharmacokinet. 2003, 42 (5), 461-474. 

Chen, G.S. Zhang, M.Y. Wang, Q. Ye, J.C. Zhong, X.-F. Pharmacokinetics of levonoregestrol transdermal controlled delivery system in body different parts of healthy women. 94. Reprod. Contracept. 1997,17, 275-278. 

Yu, Z. Gupta, S.K. Hwang, S.S. Cook, D.M. Duckett, M.J. Atkinson, L.E. Transdermal testosterone administration in hypogonadal men comparison of pharmacokinetics at different sites of application and at the first and fifth days of application. J. Clin. Pharmacol. 1997, 57, 1129-1138. Zobrist, R.H. Quan, D. Thomas, H.M. Stanworth, S. Sanders, S.W. Pharmacokinetics and metabolism of transdermal oxybutynin in vitro and in vivo performance of novel delivery system. Pharm. Res. 2003, 20, 103-109. Marzulli, E.N. Barriers to skin penetration. J. Invest. Dermatol. 1962, 39, 387-389. 

These linear kinetic models and diffusion models of skin absorption kinetics have a number of features in common they are subject to similar constraints and have a similar theoretical basis. The kinetic models, however, are more versatile and are potentially powerful predictive tools used to simulate various aspects of percutaneous absorption. Techniques for simulating multiple-dose behavior evaporation, cutaneous metabolism, microbial degradation, and other surface-loss processes dermal risk assessment transdermal drug delivery and vehicle effects have all been described. Recently, more sophisticated approaches involving physiologically relevant perfusion-limited models for simulating skin absorption pharmacokinetics have been described. These advanced models provide the conceptual framework from which experiments may be designed to simultaneously assess the role of the cutaneous vasculature and cutaneous metabolism in percutaneous absorption. 

Cevc G (2003) Transdermal drug delivery of insulin with ultradeformable carriers. Clin Pharmacokinet 42(5) 461 74... 

Formulations of the kind described above have been used quite widely in solubilising lipophilic drugs and vitamins, for oral, parenteral, and transdermal drug delivery. We consider the 2 design plus centre point tested in an animal model for the pharmacokinetic profile or pharmacological effect of the solubilised active substance. If each of the formulation was tested in two animals, with no testing of different formations on the same animal, the analysis would be identical to that of the solubility experiment above. The major part of the variance consists of that between animals and within the same animal o/, where cF = + a/. It is... 

These data clearly demonstrate that IPPSF flux profiles can be charactoized by five physical chemical parameters (H-acidity, H-basicity, S-Polarizability, and HjO solubility). The correlation of the AUC of the IPPSF flux profile to these parameters was high = 0.978), an important finding because AUC from skin would be the prime measure of systemic exposure in a toxicological risk assessment and could serve as the input function for a physiologically based pharmacokinetic model for a compound. The IPPSF efflux profile from skin reflected by its AUC has been previously used as the input profile for predicting in vivo human plasma-concentration time profiles after transdermal drug delivery (Riviere, Williams, etal., 1992). 

Zobrist, R.H., Quan, D., Thomas, H.M., Stanworth, S., and Sanders, S.W. (2003). Pharmacokinetics and metabolism of transdermal oxybutynin in vitro and in vivo performance of a novel delivery system. Pharmaceutical Research, 20, 103-109. 

Unlike intravascular dosage forms, in which a solution of drug is injected (usually by the intravenous route) into the systemic circulation, extravascular dosage forms are not immediately delivered into the systemic circulation. Extravascular dosage forms such as oral, intramuscular, subcutaneous and transdermal patches are meant to deliver dmg to the systemic circulation however, this systemic delivery is not instantaneous. Therefore, the pharmacokinetic equations require a term reflecting an absorption process. In order to understand multiple oral dosing, one... 

Since most oral AChEIs exhibit a dose-dependent relationship with undesirable cholinergic adverse effects, researchers have in recent years been focusing on slow-release administration to minimize the fluctuations in plasma concentration [67, 68]. Ye and coworkers have developed transdermal patches containing 4 mg of hupA with the average daily dose of 0.456 mg absorbed [68]. A recent clinical study on 30 healthy volunteers revealed that the transdermal administration provided continuous drug delivery over 120 h and the pharmacokinetic behavior in vivo... 

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