Bioavailability percutaneous absorption

Aniline is lipophilic (pKa of 4.6) and is expected to be rapidly and completely absorbed in the small intestine (Kao et al. 1978). No information on relative bioavailability following inhalation exposure was located, but as indicated by methemoglobin formation during inhalation experiments, systemic absorption by both the inhalation and the percutaneous routes is extensive. Percutaneous absorption of aniline in hairless mice was 4.7% of the nominal applied doses (Susten et al. 1990). 

Animal studies Pharmacokinetics and bioavailability of aescin was studied after oral and i.v. administration of tritiated aescin (108,109). About 66% and 33% of the dose was excreted in bile and urine, respectively, after i.v. administration. The oral bioavailability of aescin was about 12.5%. Percutaneous absorption of aescin was studied in mice and rats (110). The amounts of aescin in muscle were greater than in other organs. These results indicate that percutaneous administration of aescin could be beneficial. 

The effect of different polymer bases and additives on percutaneous absorption of these two ionic drugs are examined. Carboxyvinylpolymer (CVP), an ionic polymer film base, yields films with poor bioavailability of cationic drugs such as DIL, but is effective for films containing anionic drugs such as DSCG. In contrast, polyvinyl alcohol (PVA) and glycerol, electrically neutral bases, were used to formulate films with good bioavailability. 

Combinations of Electrolytes and Nonelectrolytes. Combinations of nonelectrolytes and electrolytes were often found to be superior to either alone at improving percutaneous absorption of DIL and DSCG. In particular, the bioavailability of DIL was increased remarkably by BL-9EX/TLP-4, Vifpant N/TLP-4, urea/TLP-4, urea/sacrosinate LN and urea/dehydrocholic acid. It is... 

Schaefer, H. and Redelmeier, T.E. (eds) (1996) Skin barrier. Principles of percutaneous absorption. Karger AG, Basel. Cleary, G.W. (1993) Transdermal Delivery Systems A Medical Rationale. In Topical Drug Bioavailability, Bioequivalence, and Penetration. (Shah, V.P. and Maibach, H.I., eds). Plenum Press, New York, pp. 17-68. 

Gorsline, J. Okerholm, R.A. Rolf, C.N. Moos, C.D. Hwang, S.S. Comparison of plasma nicotine concentrations after application of nicoderm (nicotine transdermal system) to different skin sites. J. Clin. Pharmacol. 1992,32, 576-581. Wester, R.C. Maibach, H.I. Bucks, D.A.W. In vivo percutaneous absorption of paraquat from hand, leg and forearm of humans. J. Toxicol. Environ. Health 1984, 14, 759-762. Taskovich, L. Shaw, J.E. Regional differences in the morphology of human skin correlation with variations in drug permeability. J. Invest. Dermatol. 1978, 70, 111. Roberts, M.S. Eavretto, W.A. Meyer, A. Reckmann, M. Wongseelashote, T. Topical bioavailability of methyl sahcy-late. Aust. N.Z. J. Med. 1982, 12, 303-305. 

When the transdermal penetration of a drug is inadequate to achieve and maintain a plasma concentration above the minimum therapeutic concentration required to produce the desired effect, a lipophilic prodrug that will be metabolized in the epidermis to the active drug could be used in the development of a controlled-release transdermal delivery system. This approach has been applied to estradiol esters (diacetate and valerate) which are rapidly converted by esterases in the skin tissue to estradiol (Chien et al, 1985). The prodrug serves to increase the transdermal bioavailability of the active drug to which it is converted by metabolism (generally ester hydrolysis) during the percutaneous absorption process. 

Reifenrath WG et al., Percutaneous absorption of explosives and related compounds An empirical model of bioavailability of organic nitro compounds from soil, Toxicol. Appl. Pharmacol., 182, 160, 2002. 

In eontrast, estimation of exposure from the use of hair care products presents a different set of eonsiderations relative to skin care products (Dressier, 1998). In partieular, the assmnptions for the calculation of percutaneous absorption for hair dyes are unique to these types of products. Factors that should be eonsidered inelude the sporadie use of the product, consequential scalp exposme to the dye material, the nature of the dye itself (permanent semipermanent), and alterations in potential bioavailability eaused by desquamation. 

Misuse of various chemicals including industrial pesticides, toxic substances, and chemical warfare agents (CWAs) requires adequate personal protective equipment and immediate skin decontamination [151]. Since the time of World War 11, scientists have made a concerted effort to improve prophylactic and therapeutic interventions to counteract cutaneous exposure to CWAs [147]. To curtail dermal systemic exposure to environmental contaminants, most material safety data sheets (MSDSs) recommend either water rinsing or soap-and-water decontamination to remove chemicals from the skin surface [152, 153]. However, it is vital that the skin be washed in such a way that does not elicit the wash-in (W-I) effect [154], The W-1 effect is defined as an enhancement of percutaneous absorption elicited specifically by skin decontamination, particularly with water. It simply means that as some chemical contaminants are washed off the skin, the chemical substance may also wash into the skin and thus become more systemically bioavailable. 

There are abundant examples in the literature that demonstrate the direct relationship between dissolution rate and bioavailability. One such example is that of piroxicam (Figure 7.6), a potent non-steroidal anti-inflammatory drug that was launched in 1981 by Pfizer for multiple conditions such as arthritis (osteoarthritis and rheumatoid arthritis) and spondylitis. It is a zwitterionic drug (p ai = 1S6 and p a2 = 5.46) and is classified as a low solubility and high permeability drug (i.e., class II) based on the Biopharmaceutics Classification System (BCS). In an attempt to improve its bioavailability after oral administration, the authors prepared three different ethanolamine salt forms i.e., mono-, di- and triethanolamine salts). These salt forms were selected based on prior literature precedence where they enhanced the percutaneous absorption of piroxicam.PK studies of the ethanolamine salts revealed that both the exposure (AUC) and the C ax of piroxicam in plasma followed the same trend as the dissolution profile at pH 6.8, which varied in the order mono- > di- > tri-piroxicam. The monoethanolamine salt showed the highest exposure with the relative bioavailability increasing almost 1.9-fold, while the di- and tri- salts were 1.7 times better than piroxicam. The C ax values showed 2.14-, 1.6- and... 

Comparison of previous exposure versus the intended cosmetic exposure can be initiated. Previous human exposure is researched. Exposure data by the dermal route, the route of application by cosmetics, will be limited. In order to proceed to the comparison of the previous exposure and intended exposure, it will be necessary to at least estimate the percutaneous absorption of the consitutents of both the comparator and the intended botanical. It is well known the topical application and oral ingestion often result in different proportions of the applied dose entering the body. The difference in bioavailability results mainly from a more extensive metabolism in the intestine and liver compared to skin, and a slower and incomplete transfer across the skin compared to the intestinal wall. The weight of evidence based approach is the so called history of safe use." Recently this concept has been accurately described by Constable (47) and it application in the safety of plant and plant-derived ingredients has been comprehensively discussed by Knudsen (48). 

The lack of activity after oral administration for most peptides and proteins resulted in the past besides parenteral application into the utilization of nonoral administration pathways, for example, nasal, buccal, rectal, vaginal, percutaneous, ocular, or pulmonary drug delivery [27]. Drug delivery via these administration routes, however, is also frequently accompanied by presystemic degradation processes. Bioavailability of numerous peptides and proteins is, for example, markedly reduced after subcutaneous or intramuscular administration compared to their intravenous administration. The pharma-cokinetically derived apparent absorption rate constant is thus the combination of absorption into the systemic circulation and presystemic degradation at the absorption... 

The oral bioavailability of GTN is only 6% while the sublingual bioavailability is 80% and the percutaneous bioavailability is also high. These data are not surprising when we consider that sublingual and percutaneous routes of absorption avoid first-pass metabolism and offer... 

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