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PubMed1999

Transdermally delivered peroxovanadium can lower blood glucose levels in diabetic rats.

The element vanadium can have insulin mimetic properties and therefore has been suggested as a possible therapeutic agent for treatment of diabetes. A series of peroxovanadium compounds that are more potent at lowering blood glucose levels than sodium metavanadate, sodium orthovanadate and vanadyl sulfate have recently been synthesized. These compounds probably will not be orally active so transdermal administration is a potential option. A patch containing either the peroxovanadium compound [VO(O2)2 1-10 phenanthroline], abbreviated bpV(phen), or placebo was placed on the back of streptozotocin induced diabetic rats and was delivered either passively (16 h) or iontophoretically (0.5 mA/cm2 for 4 h). Blood samples were analyzed for glucose and vanadium levels. Mean blood glucose levels were 83+/-1% and 109+/-1% of the starting values for animals iontophoretically treated with bpV(phen) and vehicle, respectively. The compound's insulin mimetic properties were evident within 60 min of current initiation. Blood glucose levels were reduced to 74+/-14% of the original level after 16 h of passive treatment. The compound was ineffective when fed to animals. Transdermal delivery of bpV(phen) resulted in significantly greater blood levels of vanadium than the orally delivered compound (P<0.05). Overall these experiments demonstrate that peroxovanadium delivered through the skin can lower blood glucose levels in rats. Further experiments are warranted to better characterize the nature of the response and to determine the potential for using these compounds in humans.

Administration, Cutaneous↗
PubMed1995

Intermittent transdermal nitroglycerin therapy. Decreased anginal threshold during the nitrate-free interval.

BACKGROUND: Intermittent transdermal nitroglycerin therapy is effective in the treatment of stable angina and prevents the development of tolerance. Previous investigations have suggested that removal of nitroglycerin patches may be associated with a decrease in anginal threshold. This study examines the effect of nitroglycerin patch removal on anginal threshold in a group of patients with stable angina. METHODS AND RESULTS: Twelve patients with stable angina were enrolled in a randomized, double-blind, placebo-controlled, crossover study. These patients had reproducible treadmill walking times and were taking no other long-acting antianginal medications or vasodilators. They received 0.8 mg/h transdermal nitroglycerin or wore a matching placebo patch for 5 to 7 days and then crossed over to the other treatment arm of the study. Transdermal nitroglycerin was applied at 8:00 PM and removed at 8:00 AM each day. On the last day of each treatment period, patients underwent treadmill exercise testing at 8:00 AM (before patch removal) and at 2, 4, and 6 hours after patch removal. The primary end point was the treadmill walking time until moderate angina (P2). Other end points included the treadmill walking time until onset of angina (P1), the amount of ST segment depression at P1 and P2, and treadmill walking time until the development of 1 mm ST depression. Heart rate, systolic blood pressure, and the rate-pressure product were determined at rest before exercise and at P1 and P2. At 8:00 AM P1 and P2 were not significantly affected by active nitroglycerin compared with placebo, indicating the development of tolerance. Removal of the active transdermal nitroglycerin patch was associated with a significant decrease in the time to P1 at 2, 4, and 6 hours after patch removal compared with placebo. There was also a decrease in the time to P2 after active patch removal that was statistically significant compared with placebo at 2 and 4 hours and was of borderline significance at 6 hours. There were no differences in heart rate, blood pressure, or amount of ST segment depression at either P1 or P2 after active compared with placebo patch removal. CONCLUSIONS: In patients with stable angina pectoris, intermittent transdermal nitroglycerin therapy is associated with a decrease in anginal threshold for 4 to 6 hours after patch removal. Although the cause of this phenomenon remains uncertain, it may be due to counterregulatory responses that develop during nitroglycerin patch application.

Administration, Cutaneous↗
PubMed1986

A community-based trial of transdermal antihypertensive therapy with clonidine (Catapres-TTS).

The effectiveness of transdermally administered clonidine using Catapres-TTS patches applied once a week was assessed in the control of mild to moderate hypertension by 16 general practitioners in 135 subjects. Following two weeks on placebo patches, subjects with mean seated diastolic pressures 90 to 104 mmHg were titrated to one, two or three patches and blood pressure responses measured at monthly intervals for three months. Satisfactory response of blood pressure to 90 mmHg or lower was obtained in 85% of patients who completed the maintenance phase; in 20 patients whose blood pressure responses did not reach 90 mmHg, a significantly higher blood pressure (mean 158/103 mmHg) occurred at entry into the trial (145/96 mmHg). Withdrawal from the trial was mainly for reasons of inadequate blood pressure control (15%) or localised skin reactions (15%). Dryness of the mouth was the only systemic side effect encountered with significant frequency and resulted in the withdrawal of three patients. Localised skin reactions were encountered in 51% of subjects, in the majority these were mild and subjects elected to continue with transdermal clonidine because of the convenience of once a week administration. Severe or generalised skin reactions were not encountered. Serum biochemical measurements, including serum lipid levels, remained unaltered. Transdermal clonidine therapy provided satisfactory blood pressure control in the majority of subjects and apart from the localised skin reactions which were largely of nuisance value, proved safe and acceptable to patients.

Administration, Cutaneous↗
PubMed2000

Nicotine-mecamylamine interactions.

OBJECTIVES: Mecamylamine blocks nicotinic cholinergic receptors and has been proposed, in combination with nicotine, as a novel therapy to aid smoking cessation. The objective of this study was to characterize the pharmacokinetic and pharmacodynamic interactions between transdermal mecamylamine and intravenous nicotine. STUDY DESIGN: Twelve cigarette smokers were studied while receiving transdermal mecamylamine 6 mg/24 h and placebo patches for 7 days each. On the fifth day of patch use, subjects received a combined infusion of deuterium-labeled nicotine and cotinine, with measurement of disposition kinetics of nicotine and cotinine, and cardiovascular and plasma catecholamine responses to nicotine. Half of the subjects were studied under alkaline urine conditions and the other half under acidic urine conditions. RESULTS: Steady-state plasma mecamylamine concentrations were twice as high (mean, 12.2 versus 6.3 ng/mL), consistent with lower renal clearance (2.1 versus 5.8 mL/min/kg) during alkaline compared with acidic urine conditions. Mecamylamine did not significantly affect the clearances of nicotine or cotinine. Mecamylamine significantly reduced the volume of distribution and inhibited the cardioacceleratory and epinephrine-releasing effects of nicotine. CONCLUSIONS: Mecamylamine has little effect on the clearance of nicotine and is not expected to affect steady-state levels during transdermal nicotine dosing. The reduction of the volume of distribution of nicotine by mecamylamine suggests that part of the antagonism of nicotinic central nervous system effects by mecamylamine may be due to a pharmacokinetic interaction-most likely decreased transport of nicotine into the brain or decreased binding to nicotine receptors. Mecamylamine may decrease the potential adverse cardiovascular effects of coadministered nicotine.

Administration, Cutaneous↗
PubMed1997

New developments in topical estrogen therapy.

OBJECTIVE: To review new developments in transdermal E2 therapy in postmenopausal women. DESIGN: A bibliographic search (Medline) of the medical literature from 1966 through 1995 was used to identify new studies evaluating transdermal E2. PATIENT(S): Menopausal and postmenopausal women. RESULT(S): Like oral estrogen, transdermal E2 relieves menopausal symptoms, reverses urogenital atrophy, and conserves bone economy. Initial studies have demonstrated beneficial effects of transdermal E2 on cardiovascular function. Quality of life, patient satisfaction, and compliance also improve with transdermal E2. Advances in transdermal delivery continue to emerge, including low-dose systems and patches that maintain serum E2 levels for a full 7-day period. CONCLUSION(S): New developments in transdermal administration have the potential to increase the number of postmenopausal women who accept and are compliant with long-term estrogen replacement therapy.

Administration, Cutaneous↗
PubMed2001

A pilot study assessing the impact of heat on the transdermal delivery of testosterone.

This study evaluated the effect of locally applied heat on the transdermal delivery of testosterone. Six healthy adult volunteers were tested three times while receiving a 5 mg androgen patch, the same patch with a heat-generating patch, and no patch at all over 12 hours. Statistically significant differences in mean maximum serum testosterone concentration values were seen. Heat plus patch resulted in a mean maximum serum testosterone concentration of 939 ng/dl versus 635 ng/dl (patch only) and 425 ng/dl (no patch). (Heat + patch vs. no patch: p < 0.001; heat + patch vs. patch: p < 0.001; patch vs. no patch: p = 0.003.) The area under the curve of plasma testosterone concentration versus time values were means of 4114 ng/dl.h versus 1985 ng/dl.h for the patch-only group (p = 0.001). The use of heat improved absorption of transdermal testosterone and decreased time to peak serum testosterone concentrations, resulting in a statistically significant difference in mean maximum serum testosterone concentrations compared with the use of the patch without heat.

Administration, Cutaneous↗
PubMed1992

Tobacco dependence and the nicotine patch. Clinical guidelines for effective use.

OBJECTIVE: A comprehensive review of transdermal nicotine treatment for tobacco dependence, with recommendations derived from the research literature. DATA SOURCES: English-language clinical trials. STUDY SELECTION: Clinical trials using placebo-controlled, double-blind methodology (11 studies) with at least 6 months of follow-up after treatment (eight studies) and biochemical verification of smoking status. DATA SYNTHESIS: Nicotine patches produce end-of-treatment smoking cessation rates that range from 18% to 77%; these rates are about twice those of placebo-treated subjects. Nicotine patches produced 6-month abstinence rates of 22% to 42%, while placebo patches produced quit rates of 5% to 28%. Nicotine patches appear to reduce some, but not all, nicotine withdrawal symptoms. For instance, while the patch reduces craving for cigarettes and negative moods, it does not appear to reduce hunger or weight gain. The clinical trials literature suggests that proper adjuvant smoking cessation counseling is crucial in determining successful long-term outcome with the nicotine patch, and suggests that 6 to 8 weeks of patch therapy may be an adequate duration for most patients. CONCLUSIONS: Nicotine patches are an effective aid to tobacco dependence treatment. However, success rates vary greatly across research studies and may be influenced highly by the nature and intensity of adjuvant smoking cessation counseling. More research is needed to identify optimal duration, dosage, and individualization of patch therapy. The impact of nicotine patches (more than 5 million users with $1 billion in sales for 1992) also raises important ethical and public health issues.

Administration, Cutaneous↗
PubMed2003

Transdermal delivery of paracetamol for paediatric use: effects of vehicle formulations on the percutaneous penetration.

Paracetamol is a safe and effective analgesic and antipyretic agent, and is one of the most widely used medications for infants and children. The formulations currently available have been designed for oral and rectal administration. However, they are not practical in young patients with vomiting and diarrhoea, or in those who refuse to take the full dose. An alternative route of administration would be a significant contribution to the paediatric pharmacopoeia. The aim of this study was to develop a new transdermal system for optional therapeutic administration of paracetamol in infants and children. In-vivo studies were carried out in animals using a transdermal system of high-loaded, soluble paracetamol in a hydrogel patch, which was also tested in-vitro for 8 h. Although the beneficial contribution of glyceryl oleate to the transdermal penetration of paracetamol seemed to be significant in-vitro, it was shown to be insufficient in-vivo. To improve the penetration of the drug, 4% PEG-40 stearate and 10% ethanol were incorporated as absorption enhancers into the dermal patches. A few hours after application of the improved patches to rats, plasma drug concentrations were elevated to levels comparable with those obtained after oral and subcutaneous administration of a high dose of paracetamol. Since plasma drug concentrations did not reach a constant steady state (as a peak or plateau) during the short-term animal experiments, longer pharmacokinetic studies in conscious animals are necessary.

Acetaminophen↗
PubMed2003

Transdermal glyceryl trinitrate for prevention of post-ERCP pancreatitis: A randomized double-blind trial.

BACKGROUND: Pancreatic sphincter hypertension increases the risk of pancreatitis in patients undergoing ERCP. Glyceryl trinitrate reduces sphincter of Oddi pressure. This study tested the hypothesis that transdermal glyceryl trinitrate could be effective in the prevention of post-ERCP pancreatitis. METHODS: One hundred forty-four patients undergoing ERCP were randomized: 71 received a 15-mg glyceryl trinitrate patch (glyceryl trinitrate group) and 73 a placebo patch (control group). RESULTS: In the control group, post-ERCP pancreatitis developed in 11 patients versus 3 in the glyceryl trinitrate group (p < 0.05). Twenty-four hour to baseline serum amylase and lipase ratios were lower in the glyceryl trinitrate group (respectively, 3.6 vs. 7.5, p < 0.05; and 5.3 vs. 27.7, p < 0.05). In a multivariate analysis, glyceryl trinitrate patch and the number of pancreatic injections, but not endoscopic sphincterotomy, were independent risk factors for post-ERCP pancreatitis. CONCLUSIONS: The results of this study suggest that use of a transdermal glyceryl trinitrate patch protects against post-ERCP pancreatitis.

Administration, Cutaneous↗
PubMed1999

Predictors and timing of adverse experiences during trandsdermal nicotine therapy.

OBJECTIVES: Difficulty sleeping is a recognised tobacco withdrawal symptom, but sleep problems, like application site reactions, are commonly reported as adverse reactions to transdermal nicotine therapy. However, no studies have examined potential predictive factors associated with the occurrence of expected adverse experiences during transdermal nicotine therapy. The subject of skin tolerability among patients with a history of eczema, psoriasis or other skin disorders is of particular interest, as are the relationships between plasma concentrations of nicotine, concurrent smoking, sleep problems and nausea. METHODS: The cohort study involving 1392 participants was designed to assess the timing, severity and predictive factors of adverse experiences reported during 24-hour transdermal nicotine therapy. Data were collected on patients aged 18 to 70 years old who were smokers and who had expressed a strong desire to stop smoking. The intervention consisted of brief behavioural counselling, a booklet containing smoking cessation advice and instructions for use of the patches, and a 12-week course of decreasing transdermal nicotine doses. RESULTS: Follow-up was available on 1392 out of 1481 study participants. The majority of adverse experiences were mild. Sleep problems occurred in 669 out of 1392 (48%) participants and most often commenced on the day of smoking cessation. Application site reactions occurred in 478 out of 1392 (34%) participants and most often occurred after 6 days of therapy. No predictor had an adjusted hazard ratio above 2. Statistically significant (p < 0.05) predictors of sleep problems were successfully quitting smoking and female gender. Predictors of application site reactions were psoriasis or eczema, other skin conditions, age <40 years, female gender, place of birth outside Australasia, and trade or university education level. Substantially increased nicotine intake during therapy compared with baseline smoking occurred in 8% of participants who smoked concurrently, and 4% of participants who did not (p = 0.1). Increased nicotine intake was associated with a modest increase in the overall rate of adverse experiences (89% vs 63%, p = 0.04) and dizziness/lightheadedness (17% vs 3%, p = 0.03), but not with sleep problems or cardiovascular events. CONCLUSIONS: Transdermal nicotine therapy appears to be well tolerated, even if the user smokes concurrently. Sleep disturbance during therapy appeared to be primarily associated with tobacco withdrawal rather than with nicotine excess from treatment with transdermal nicotine. Study participants with pre-existing skin disorders were somewhat more likely to report mild application site reactions than other participants.

Administration, Cutaneous↗
PubMed2000

Randomized comparison of intranasal and transdermal estradiol.

OBJECTIVE: To compare the efficacy and patient acceptability of intranasal versus transdermal 17 beta-estradiol (E2) delivery systems for postmenopausal symptoms. METHODS: Postmenopausal women were randomly assigned to intranasal 17 beta-E2, 300 microg daily (n = 176) or transdermal 17 beta-E2 (delivering 50 microg/day), two patches per week (n = 185) for 12 weeks, followed by a 4-week period with the alternate treatment. Efficacy was compared between groups using the Kupperman Index and vasomotor symptoms at week 12. Patient acceptability was compared by patient choice of administration route and by questionnaire at week 16. RESULTS: Intranasal and transdermal therapy produced significant reductions in the Kupperman Index and in the occurrence of hot flushes and night sweats at week 12. Alleviation of climacteric symptoms was statistically equivalent in the two treatment groups (P <.001). The difference between groups in the Kupperman Index score of -0.5 +/- 0.9 (95% confidence interval -2.3, 1.3) was within the predetermined interval of equivalence. Both therapies were well tolerated with similar adverse event rates, except for moderate and severe mastalgia which was significantly less frequent with intranasal E2 (7.2%) than with the patch (15.5%, P =.02). Sixty-six percent of patients chose to continue the intranasal therapy and 34% the transdermal therapy (P <.001). Satisfaction was greater with intranasal therapy at week 16 (P <.001). CONCLUSION: Intranasal and transdermal estrogen delivery systems had equivalent efficacy and similar safety profiles. Intranasal therapy was the patients' choice for long-term treatment.

Administration, Cutaneous↗
PubMed2006

Effects of transdermal testosterone administration on insulin sensitivity, fat mass and distribution, and markers of inflammation and thrombolysis in human immunodeficiency virus-infected women with mild to moderate weight loss.

OBJECTIVE: To determine the effects of raising serum T levels into the high normal female range by transdermal T administration on insulin sensitivity, fat volume, and markers of inflammation and thrombolysis in HIV-infected women with recent weight loss. DESIGN: Placebo-controlled, randomized clinical trial. SETTING: Academic clinical research center. PATIENT(S): Fifty-two HIV-infected, menstruating women with >5% weight loss over the prior 6 months and current T<33 ng/dL. INTERVENTION(S): Placebo or T patches twice weekly for 24 weeks to achieve nominal delivery of 300 microg T daily. MAIN OUTCOME MEASURE(S): Testosterone by liquid chromatography-tandem mass spectrometry, insulin sensitivity by the frequently sampled intravenous glucose tolerance test (FSIVGT), abdominal and thigh fat volumes by magnetic resonance imaging (MRI), and C-reactive protein (CRP) as a measure of inflammation and plasminogen-activated inhibitor-1 (PAI-1) levels as a marker of thrombolysis. RESULT(S): Serum and free T levels significantly increased into the high normal female range in T-treated but not placebo-treated women. Insulin sensitivity by FSIVGT, whole body, thigh SC, and intra-abdominal fat volumes, and CRP and PAI-1 levels did not change significantly in either group and were not significantly different between the two groups. Fasting insulin increased in the placebo group and fell slightly in the T group, resulting in significant differences in change between groups. CONCLUSION(S): Twenty-four weeks of elevation of serum T levels into the high normal female range in HIV-infected women with mild to moderate weight loss by transdermal T patches did not adversely affect insulin sensitivity, whole-body fat mass or regional fat distribution, or markers of inflammation and thrombolysis. More prolonged and larger studies are needed to determine the effects of higher doses of T on body composition and insulin sensitivity in women.

Administration, Topical↗
PubMed1994

Rapid development of nitrate tolerance in healthy volunteers: assessment using spectral analysis of short-term blood pressure and heart rate variability.

Nitrate tolerance is characterized by a loss of nitroglycerin (NTG) vasodilating and hypotensive effects during continuous administration, but is difficult to detect clinically. We hypothesized that the decrease in arterial blood pressure (BP) and the reflex sympathetic activation and tachycardia due to baroreflex deactivation associated with rapid intravenous (i.v.) infusion of NTG would be decreased during continuous NTG patch therapy as a result of tolerance to transdermal NTG. Sympathetic activation was measured as the change in amplitude of low-frequency (66-129 mHz) oscillations in BP and heart rate (HR) recorded by a noninvasive method. Eleven healthy male volunteers received rapid i.v. infusion of 0.45 mg NTG in 1 min on 3 consecutive days: before NTG patch, after 22.5 h of patch therapy, and 22.5 h after patch removal. The maximum decrease in systolic BP (SBP) and maximum reflex tachycardia as well as the sympathetic activation produced by i.v. NTG were compared during each of the three study periods. The maximum decrease in SBP was 38 +/- 8 mm Hg before NTG patch and 27 +/- 15 mm Hg during NTG patch (p < 0.05), with return to baseline values (37 +/- 13 mm Hg) after patch removal. There was no significant change in amplitude of reflex tachycardia among study periods. However, low-frequency oscillations in SBP increased by 40 +/- 31% in the absence of NTG patch and by only 9 +/- 35% after 22.5 h of patch therapy (p < 0.05). Patch removal resulted in a significant rebound increase in these oscillations (70 +/- 51%; p < 0.05 vs. baseline).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1998

Usage patterns of transdermal nicotine when purchased as a non-prescription medicine from pharmacies.

OBJECTIVE: To assess nicotine patch use in smokers who purchased the product as a non-prescription medicine from pharmacies. DESIGN: A questionnaire administered at the time of purchase. SETTING: Community pharmacies throughout New Zealand. SUBJECTS: A total of 805 male and female purchasers of nicotine patches aged 18 through 87 years. MAIN OUTCOME MEASURES: Patterns of usage including self-reported smoking history, previous quit-smoking attempts, previous and current use of transdermal nicotine and other products, side effects, and concomitant smoking. RESULTS: Most respondents (74%) had attempted to quit smoking previously, many of whom (53%) had used a non-prescription nicotine replacement product. Approximately 60% of purchasers were first-time users. For those continuing a course of treatment, there was no evidence of use for longer than the manufacturer's recommendation (12 weeks). Twenty-eight per cent of respondents reported continuing smoking while using transdermal nicotine, although the number of cigarettes smoked was much less than in the reported smoking history. Side effects were reported by 24% of patch users in the current course, but there was no evidence of significant safety problems. CONCLUSIONS: This survey provides preliminary data on the non-prescription usage of transdermal nicotine when purchased through pharmacies.

Administration, Cutaneous↗
PubMed1991

Contrasting effects of oral and transdermal routes of estrogen replacement therapy on 24-hour growth hormone (GH) secretion, insulin-like growth factor I, and GH-binding protein in postmenopausal women.

Estrogen deficiency may account for lower circulating GH and insulin-like growth factor I (IGF-I) concentrations in the menopause. Since the liver is the major source of circulating IGF-I and oral estrogens have nonphysiological effects on hepatic function, we have compared GH secretion over 24 h from 20 min sampling and serum IGF-I levels in premenopausal women (n = 7, follicular phase) and postmenopausal women before and after 2 months of cyclical replacement therapy with either oral ethinyl estradiol (EE, 20 micrograms daily; n = 7) or transdermal 17 beta-estradiol (E2, 100 micrograms patches applied twice weekly; n = 7). The extent of GH binding to its serum binding protein was also examined by measuring the percent specific binding of [125I] GH in serum. Mean 24-h serum GH and serum IGF-I were significantly lower (P less than 0.05) in postmenopausal than in premenopausal women. Oral and transdermal estrogen therapy resulted in a comparable degree of gonadotropin suppression. Oral EE treatment increased mean 24-h serum GH (2.0 +/- 0.4 to 7.0 +/- 0.6 mIU/L, P less than 0.0005) and mean pulse amplitude (5.3 +/- 1.2 to 11.2 +/- 2.5 mIU/L, P less than 0.01) but significantly reduced circulating IGF-I (0.70 +/- 0.09 to 0.47 +/- 0.04 U/mL, P less than 0.02) levels. Oral EE increased the percent specific binding of [125I]GH (22.0 +/- 1.6 to 32.0 +/- 1.9%, P less than 0.0005), however the derived mean 24-h free serum GH concentrations were significantly higher (P less than 0.0005) after treatment. By contrast, transdermal E2 administration, which restored circulating E2 concentrations to the midfollicular range, increased circulating IGF-I (0.86 +/- 0.15 to 1.10 +/- 0.14 U/mL, P less than 0.005) to levels that were not significantly different from those of premenopausal women (1.41 +/- 0.21 U/mL). This was not accompanied by changes in 24-h GH secretion or the percent specific binding of [125I]GH in serum. The route of administration is a major determinant of the effects of exogenous estrogens on the GH/IGF-I axis. Oral estrogen administration inhibits hepatic IGF-I synthesis and increases GH secretion through reduced feedback inhibition. Reduced GH secretion in the menopause is not explained by estrogen deficiency since GH secretion is not restored by the attainment of physiological E2 concentrations using the transdermal route. The contrasting route dependent IGF-I responses have important implications for the long-term benefit of hormone replacement therapy in the menopause.

Administration, Cutaneous↗
PubMed1991

Administration of antidiuretic peptide (DDAVP) by way of suction de-epithelialised skin.

Transdermal drug delivery seems a promising way of achieving complete, predictable absorption, but the epidermis is a barrier for most drugs. A new technique for transdermal drug delivery, in which a small patch of epidermis was removed, was tested in seven healthy volunteers by means of the antidiuretic peptide 1-deamino-8-D-arginine vasopressin (DDAVP). The epithelium of a small area of forearm skin (diameter 5 mm) was removed painlessly, and in a standard way, by a simple device operating at a present vacuum. DDAVP was given by way of improvised occlusive reservoirs. Plasma DDAVP concentration/time curves conformed closely with zero-order kinetics, which suggests that the bioavailability approached 100%, corresponding to that for direct intravenous infusion. Four volunteers were given DDAVP daily for 4 days by way of the de-epithelialised site; there were no signs that re-epithelialisation hindered permeation. All plasma DDAVP values substantially exceeded the lowest effective therapeutic concentration for patients with diabetes insipidus. The vacuum removal of the epithelium caused pronounced hyperaemia in the de-epithelialised dermis (assessed by laser doppler flow measurement); the hyperaemia persisted, unaffected by DDAVP, and may have contributed to the efficient permeation. The skin spot appeared normal at 6 weeks.

Administration, Cutaneous↗
PubMed1998

Estrogen regulation of adipose tissue lipoprotein lipase--possible mechanism of body fat distribution.

OBJECTIVE: The purpose of this study was to evaluate the regulation of lipoprotein lipase activity, protein mass, and messenger ribonucleic acid by estradiol. STUDY DESIGN: Premenopausal women not taking exogenous sex steroids had transdermal 17 beta-estradiol and placebo patches placed in the gluteal region during the early follicular phase of the menstrual cycle. Adipose biopsies were performed from beneath the patches. Adipose tissue lipoprotein lipase activity was determined by a radiometric assay, protein mass was determined by enzyme-linked immunosorbent assay, and messenger ribonucleic acid level was determined by Northern analysis. Comparisons between the treated and placebo sides were analyzed by nonparametric statistics. RESULTS: Adipose tissue from beneath the 17 beta-estradiol patch had significantly decreased lipoprotein lipase activity and extracellular protein mass than did adipose tissue from beneath the placebo patch. There was no difference in lipoprotein lipase messenger ribonucleic acid levels. CONCLUSION: Estrogen decreases lipoprotein lipase activity by a posttranscriptional modification of protein levels. A hypothesis of sex steroid regulation of body fat distribution is proposed.

Adipose Tissue↗
PubMed2000

Ethosomes - novel vesicular carriers for enhanced delivery: characterization and skin penetration properties.

This work describes a novel carrier for enhanced skin delivery, the ethosomal system, which is composed of phospholipid, ethanol and water. Ethosomal systems were much more efficient at delivering a fluorescent probe to the skin in terms of quantity and depth, than either liposomes or hydroalcoholic solution. The ethosomal system dramatically enhanced the skin permeation of minoxidil in vitro compared with either ethanolic or hydroethanolic solution or phospholipid ethanolic micellar solution of minoxidil. In addition, the transdermal delivery of testosterone from an ethosomal patch was greater both in vitro and in vivo than from commercially available patches. Skin permeation of ethosomal components, ethanol and phospholipid, was demonstrated in diffusion-cell experiments. Ethosomal systems composed of soy phosphatidylcholine 2%, ethanol 30% and water were shown by electron microscopy to contain multilamellar vesicles. 31P-NMR studies confirmed the bilayer configuration of the lipids. Calorimetry and fluorescence measurements suggested that the vesicular bilayers are flexible, having a relatively low T(m) and fluorescence anisotropy compared with liposomes obtained in the absence of ethanol. Dynamic light scattering measurements indicated that ethanol imparted a negative charge to the vesicles. The average vesicle size, as measured by dynamic light scattering, was modulated by altering the ethosome composition. Experiments using fluorescent probes and ultracentrifugation showed that the ethosomes had a high entrapment capacity for molecules of various lyophilicities.

Animals↗