Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042109 (urticaria)
 6,569 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This review of the research and development of transdermal delivery systems for levonorgestrel and combinations of levonorgestrel and estrogens also contains explanatory material on skin structure and absorption of drugs by diffusion and partition, permeability and use of enhancers to facilitate absorption, use of pro-drugs and derivatives, and cutaneous side effects. Drug absorption entails diffusion through the lipophilic stratum corneum and the hydrophilic epidermis, and between the two layers. Diffusion of levonorgestrel is driven by the saturated solution in the medium, such as ethanol, but the rate was insufficient. The target delivery rate for levonorgestrel used alone as a contraceptive is 35 mcg/day for transdermal use, which would require a delivery rate of 0.3 mcg/sq.cm. Ethyl acetate was found to be the best "penetration enhancer," speeding absorption 17-fold in rat skin. Levonorgestrel in ethyl acetate diffused through human cadaver skin at a rate requiring a patch of 7.5 sq. cm. Use of pro-drugs and derivatives is based on the theory that even though the derivative may diffuse more slowly because of its larger size, it is more soluble in both lipophilic and hydrophilic media. The best pro-drug was levonorgestrel-glycidol, with a 32-fold increase in penetration. Pro-drugs have the drawback of requiring complete FDA approval. They are hydrolyzed in skin to the native steroid, however. The type of transdermal delivery system needed for levonorgestrel is a membrane-based patch with a reservoir. Ethylene vinyl acetate copolymer systems have been tested or rabbits and in Phase I clinical trials. The micro-reservoir systems has been marketed for estradiol in a 3.5-day patch. A similar system has been developed experimentally using levonorgestrel and estradiol combined. Most transdermal systems cause mild skin irritation in a high proportion of users, but the likelihood of contact allergy or urticaria with levonorgestrel is minimal. Development of a transderm system with levonorgestrel and ethyl acetate, which is generally recognized as safe (GRAS), would be feasible as soon as the stability of levonorgestrel in ethyl acetate is defined.
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PMID:Transdermal delivery of levonorgestrel. 189 13

This comprehensive review of transdermal delivery systems for estrogens and progestins covers skin structure and absorption of chemical agents by diffusion and partition, permeability and use of enhancers to speed absorption, choices of drugs for transdermal contraceptives, animal and clinical work with estradiol, ethinyl estradiol and levonorgestrel, use of pro-drugs and derivatives, types of transderm delivery systems, metabolism of these drugs by skin and skin flora, and cutaneous side effects, all illustrated graphically and mathematically. Drug absorption entails diffusion through the primarily and mathematically. Drug absorption entails diffusion through the primarily lipophilic stratum corneum, and the hydrophilic epidermis: transport between these layers is often the rate-limiting step. For many drugs, permeability enhancers such as dimethyl sulfoxide, ethanol and ethyl acetate are needed. Good drug candidates for transdermal application must be potent in low doses, have short half-lives, not elicit an allergic response nor be extensively metabolized in skin. The permeability of levonorgestrel has been increased by using esters, and "pro-drugs" which are compounds that increase polarity, but are degraded to the active drug by skin tissue. The estrogens are subject to a minor degree of oxidation, and no significant degradation by skin microbes. There are 3 types of transdermal systems: the membrane, matrix and drug reservoir types. The Estraderm brand system for estradiol is a membrane-moderated design with ethanol as the chemical enhancer. Skin penetration is the rate-limiting step. Levonorgestrel as been tested with ethyl acetate and ethanol as penetration enhancers in rats, rabbits, and in a Phase I trial. The development of a transderm system for a combination of estrogen and progestin is a complex problem because 2 different enhancers must be used. Most transdermal systems are mild skin irritants, but incidence of contact allergy or urticaria are rare, with no cases yet reported from use of Estraderm. Transdermal application of contraceptive steroids is expected to be available eventually.
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PMID:Transdermal delivery of contraceptives. 227 99

To improve counselling information to Nigerian family planning clients, we compared non-menstrual events reported by 248 Norplant users and 214 Uniplant users. Women using Norplant were significantly older and of higher parity and greater contraceptive experience than Uniplant users. Other admission characteristics of the two groups were similar. The total women-months of use of Norplant was 2,946 (mean 11.9 +/- 0.6 SE) months while that for Uniplant was 2,315 (mean 10.8 +/- 0.2 SE) months. About 36% of Norplant users and 15% of Uniplant users reported non-menstrual adverse events, the commonest ones being pain/itching at the insertion site, unexplained low abdominal pains and clinically diagnosed pelvic inflammatory disease (PID). The numbers of women reporting drug-related adverse events were 61 (24.6%) and 23 (10.8%), respectively, among Norplant and Uniplant users. Drug-related serious adverse events were reported by 3 (1.2%) Norplant users and 5 (2%) Uniplant users. The adverse events leading to Uniplant removal were severe urticaria, breast lumps, pruritus vulvae, headache with raised blood pressure, adnexal pains and ovarian cysts, and static weight while those leading to Norplant removal were breast lump and headache with raised blood pressure. Weight gain was reported by only 7 (3%) of Norplant users. Although of no serious clinical consequences, drug-related adverse events should be added to the counselling information to prospective users.
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PMID:Nonmenstrual adverse events associated with subdermal contraceptive implants containing normegestrel and levonorgestrel. 1503 62