Transdermal administration pharmacokinetics

Pharmacokinetics Absorbed slowly after transdermal administration. Protein binding 5%. Metabolized in the liver. Excreted primarily in urine. Half-life 4 hr. 

Zobrist RH, Schmid B, Feick A, et al. Pharmacokinetics of the R- and S-enantiomers of oxybutynin and N-desethyloxybutynin following oral and transdermal administration of the racemate in healthy volunteers. PharmRes 2001 18 1029-1034. 

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.)...

The pharmacokinetic profile of hupA has been studied in healthy volunteers with oral as well as transdermal administration [66, 67]. In a recent study, hupA was administrated p.o. to 12 healthy, young volunteers as a single therapeutic dose of 0.4 mg and was found to be well tolerated with no adverse events reported. HupA was absorbed rapidly, and occurred in the plasma 5-10 min after administratimi and reached Cmax 2.59 ng ml at a 7]nax of 58.33 min. It was shown to distribute widely in the body at a moderate rate and to cross the blood-brain barrier (BBB) easily. The results conformed to a two-compartment model with the elimination half-life of oc-phase and (3-phase to be approximately 21 and 716 min, respectively [66]. Another study performed in China in 1995 which included six volunteers receiving a single 0.99 mg p.o. dose of hupA showed somewhat different results with shorter absorption and elimination half-lives, i.e., 13 and 288 min, respectively, compared to the previous study. However, both studies revealed rapid absorption and wide distribution, followed by a slower elimination rate [17, 66]. 

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... 

Wu T, Li CY, Chen M, Zhang J, Tan HS, Yang C, Ju WZ (2011) Clinic pharmacokinetic profiles of huperzine A following transdermal administration to healthy human volunteers. Chromatographia 74(l-2) 67-73. doi 10.1007/sl0337-011-2037-z... 

Some pharmacokinetic properties of the commonly used amide local anesthetics are summarized in Table 26-2. The pharmacokinetics of the ester-based local anesthetics have not been extensively studied owing to their rapid breakdown in plasma (elimination half-life < 1 minute). Local anesthetics are usually administered by injection into dermis and soft tissues around nerves. Thus, absorption and distribution are not as important in controlling the onset of effect as in determining the rate of offset of local analgesia and the likelihood of CNS and cardiac toxicity. Topical application of local anesthetics (eg, transmucosal or transdermal) requires drug diffusion for both onset and offset of anesthetic effect. However, intracavitary (eg, intra-articular, intraperitoneal) administration is associated with a more rapid onset and shorter duration of local anesthetic effect. 

Humberstone, A.J. Evans, A.M. Davis, S.R. A Comparative Study of the Pharmacokinetics of Testosterone (T) Following Administration of a Metered-Dose Transdermal Spray (MDTS(R)) to the Abdomen or Forearm in Healthy Postmenopausal Women with Low Serum Testosterone, Endocrine Society s 85th Annual General Meeting, Philadelphia, USA, 2002. 

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. 

Appell RA, Chancellor MB, Zobrist RH, et al. Pharmacokinetics, metabolism, and saliva output during transdermal and extended-release oxybutynin administration in healthy subjects. Mayo Clin Proc 2003 78 696-702. 

Kapil RP, Cipriano A, Michels GH, Perrino P, O Keefe SA, Shet MS, et al. Effect of ketoconazole on the pharmacokinetic profile of buprenor-phine following administration of a once-weekly buprenorphine transdermal system. Clin Drug Investig 2012 32(9) 583-92. 

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