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Transdermal fentanyl combined with nonsteroidal anti-inflammatory drugs for analgesia in horses.

This study investigated the pharmcokinetics, efficacy, and safety of the fentanyl transdermal therapeutic system (TTS) in horses in which there was an inadequate analgesic response to nonsteroidal anti-inflammatory drugs (NSAIDs) alone. Nine horses with pain that was refractory to therapeutic doses of phenylbutazone (n = 3) or flunixin meglumine (n = 6) subsequently also received between 39 and 110 microg/kg of transdermal fentanyl. Blood samples were collected at 0, 1, 2, 3, 4, 5, 6, 12, 24, 36, 48, 60, and 72 hours after patch application, and a radioimmunoassay was used to determine serum fentanyl concentrations. Pharmacokinetic values were determined by noncompartmental analysis. Physical examination findings were recorded in all horses, and pain and lameness grading systems were used to assign scores to 8 and 6 horses, respectively. All horses tolerated the administration of fentanyl TTS, in that no clinically significant adverse effects attributable to fentanyl were observed. Use of the TTS resulted in variable serum concentrations of fentanyl, with a peak serum concentration of 2.2+/-1.1 ng/mL (mean+/-SD) and a time to peak serum concentration of 26+/-13 hours. After transdermal fentanyl administration, mean time to reach serum fentanyl concentrations consistent with analgesia in other species (1 ng/mL) was 14 hours. In addition, serum fentanyl concentrations of 1 ng/mL or greater were maintained in all but one horse for at least 18 hours. Pain scores were significantly decreased after fentanyl TTS and NSAID administration (P < .05), but lameness scores were not significantly different (P > .05). Overall, administration of fentanyl TTS had a favorable pharmacokinetic profile in horses with clinical pain, and the fentanyl TTS in combination with NSAIDs appeared to provide safe and effective analgesia in most of the horses with pain that was refractory to NSAID therapy alone.

Administration, Cutaneous↗
PubMed1997

Transdermal delivery of erythromycin lactobionate--implications for the therapy of gastroparesis.

BACKGROUND: The treatment of many diseases may be complicated by abnormalities in gastric emptying. Gastric motor dysfunction may lead to unpredictable food and medication delivery to the small intestine, their site of absorption. Prokinetic agents improve gastric motility, but orally administered drugs are unreliably absorbed, thereby limiting their effectiveness. A method of delivering prokinetic agents which bypasses the gastrointestinal tract could lead to more effective treatment. METHODS: Skin samples from rat, hairless mouse and man were placed in an in vitro diffusion chamber. The epidermal side of the skin was exposed to erythromycin lactobionate and passage of the drug across the skin sample monitored and quantitated by high-performance liquid chromatography with UV detection. RESULTS: Erythromycin passes across all skin types tested. Steady-state flux across hairless mouse skin was greater than for rat, full thickness human skin and human epidermis. In the first 3 h following introduction of erythromycin lactobionate, 1.85 mg/cm2 crossed human epidermis. Given that a dose of 50 mg may exert prokinetic effects in vivo in man, increasing the patch size to approximately equal to 28 cm2 should provide therapeutic levels of drug within 3 h. CONCLUSIONS: Erythromycin lactobionate, when administered transdermally, can be delivered at levels sufficient to treat gastroparesis. This technique warrants in vivo investigation.

Administration, Cutaneous↗
PubMed1999

Four-week nicotine skin patch treatment effects on cognitive performance in Alzheimer's disease.

RATIONALE: Acute nicotine injections have been found to improve attentional performance in patients with Alzheimer's disease (AD), but little is known about chronic nicotine effects. OBJECTIVE: The present study was undertaken to evaluate the clinical and neuropsychological effects of chronic transdermal nicotine in Alzheimer's disease subjects over a 4-week period. METHODS: The double-blind, placebo controlled, cross-over study consisted of two 4-week periods separated by a 2-week washout period. Patients wore the nicotine patch (Nicotrol) for 16 h a day at the following doses: 5 mg/day during week 1, 10 mg/day during weeks 2 and 3 and 5 mg/day during week 4. The eight subjects had mild to moderate AD and were otherwise healthy. RESULTS: Nicotine significantly improved attentional performance as measured by the Conners' continuous performance test (CPT). There was a significant reduction in errors of omission on the CPT which continued throughout the period of chronic nicotine administration. The variability of hit reaction time (reaction time for correct responses) on the CPT was also significantly reduced by chronic nicotine. Nicotine did not improve performance on other tests measuring motor and memory function. CONCLUSIONS: The sustained improvement in attention found in this study with nicotine dermal patches is encouraging. However, the lack of detected effects of nicotine treatment on other cognitive and behavioral domains in this study leaves questions concerning the clinical impact of nicotinic treatment in Alzheimer's disease. The modest size of this study limited statistical power which may have been needed to detect more subtle but clinically significant cognitive effects. Higher doses of nicotine, other nicotinic ligands or combination treatment of nicotine with other therapies may be efficacious for producing broader therapeutic effects.

Administration, Cutaneous↗
PubMed1999

Clinical experience with transdermal clonidine in African-American and Hispanic-American patients with hypertension: evaluation from a 12-week prospective, open-label clinical trial in community-based clinics.

The objective of this study was to assess the efficacy and tolerability of transdermal clonidine in inner-city African-American and Hispanic-American patients with essential hypertension. A multiclinic open-label, prospective trial for 12 weeks was used. Dose titration was based on office blood pressure (BP) measurements of > 140/90 mm Hg. Clinical sites were community-based primary care centers. Untreated and treated hypertensive patients whose diastolic BP exceeded 90 mm Hg were administered transdermal clonidine at 0.1 mg or 0.2 mg delivery daily. The drug was titrated after 1 month if diastolic BP was greater than 90 mm Hg. At 12 weeks of treatment, change in blood pressure from baseline as well as adverse effects and patient satisfaction were assessed. A total of 357 patients entered the treatment phase of the study, and 315 patients (244 African-Americans, 67 Hispanic-Americans) had evaluable data. Transdermal clonidine significantly (P <.001) lowered BP in all patients by 15.7/12.8 +/- 18.1/9.6 mm Hg, and heart rate was reduced by 3 +/- 9 beats/min (P <.001). There were no differences in BP reduction according to race and ethnicity, gender, or age. The most common adverse effects were pruritus or discomfort at the patch site, dizziness, dry mouth, and fatigue. Eleven percent of the patients discontinued treatment because of one of these adverse effects. A large proportion of patients (67%) reported that transdermal clonidine was more convenient to use than oral therapy. Transdermal clonidine, alone or in combination with other antihypertensive therapies, significantly lowered BP and heart rate in inner-city hypertensive patients. The drug was generally well tolerated, with 89% of the patients remaining in the trial. Patient acceptability was high with the once-weekly treatment, which is an important feature for this particular hypertensive population.

Administration, Cutaneous↗
PubMed2004

Nitric oxide donors: effects on fetoplacental blood flow.

OBJECTIVE: To investigate fetal and uteroplacental blood flow after transdermal administration of glyceroltrinitrate (GTN) in pregnancies at risk for preterm delivery. STUDY DESIGN: Twenty-five pregnant women who received GTN patches (Nitroderm TTS 10) with a dosage of 0.8 mg/h, because of risk for preterm delivery, were included in the prospective study. Doppler measurements (resistance index, RI) of the umbilical artery (UA), the middle cerebral artery (MCA) and the uterine arteries of the placental (UTA-P) and the non-placental (UTA-NP) side, with calculation of the mean-RI (UTA-mean), were performed before and after 24, 48 and 72 h of the 1st GTN application. Wilcoxon test and Holm correction were used for statistical analysis. RESULTS: The initial RI values were in the normal range. Significant decreases of the RI of UTA-NP ( P = 0.02 ) and UTA-mean ( P = 0.03) were observed 24h after GTN application. The other RI values did not show significant changes. CONCLUSION: Transdermal nitroglycerine used for the treatment of preterm labour does only reduce uterine vascular impedance at the non-placental side with primary higher resistance. It does not affect fetal perfusion and uterine perfusion at the placental side with normal blood flow resistance.

Arteries↗
PubMed2000

[Contact dermatitis due to ethyl alcohol: how to perform patch tests?].

INTRODUCTION: Ethyl alcohol sensitization is rare and can induce immediate contact urticaria or delayed eczema. Patch tests performed with ethanol can provoke an irritative reaction and are not well codified. CASE-REPORTS: We report on 4 cases of contact dermatitis due to alcohol in 4 women. Eczema was due to alcohol contained in the reservoir of a transdermal transfer system with estrogens in 2 cases and related to the application of alcoholized antiseptic lotions in the other 2 cases. In 2/4 cases we observed a co-sensitization with corticosteroids. METHODS: Patch tests were performed with alcohol at 95 degrees diluted at 70 p. 100 and at 10 p. 100 in water and read after 20 minutes then on day 2 and day 4. RESULTS: Positive results were obtained in 4/4 cases when alcohol was tested diluted at 70 p. 100 in water and in 3/4 cases when diluted at 10 p. 100 in water. No irritant reaction was observed in 140 negative controls. DISCUSSION: Immediate after 20 minutes and delayed readings of patch tests performed with ethyl alcohol diluted at 70 p. 100 seem to be convenient in diagnosing cutaneous delayed hypersensitivity to alcohol. Co-sensitization between corticosteroids and alcohol could be due to an aldehyde deshydrogenase deficiency.

Administration, Topical↗
PubMed1999

Pharmacokinetics of new testosterone transdermal therapeutic systems in gonadotropin-releasing hormone antagonist-suppressed normal men.

In a phase I single-center, open, randomized pilot study with a three-way cross-over design the pharmacokinetics of three testosterone-containing transdermal therapeutic systems were evaluated in healthy male volunteers. Testosterone TTS HEXAL type 1 and 2 are nonscrotal membrane patches differing in the kind of adhesive used. 6 subjects were treated with low dose Testosterone TTS type 1, high dose Testosterone TTS type 1 and low dose Testosterone TTS type 2. To eliminate the influence of endogenous serum testosterone, the endogenous testosterone secretion was suppressed by the GnRH antagonist cetrorelix. In all subjects under GnRH antagonist treatment a marked suppression of LH, FSH, testosterone, DHT and estradiol was observed. Physiologic testosterone levels were achieved during the 24-hour-application period. Maximal serum levels were reached after 4 hours with both TTS systems. Both systems appear suited for further testing because both enable a physiological circadian profile to be achieved. GnRH-antagonist pretreatment is a useful model to evaluate the effect of exogenous testosterone in clinical studies, when, due to fluctuations in endogenous hormone levels, an estimation of the proportion of exogenous steroid is not possible.

Administration, Cutaneous↗
PubMed2005

Nebido: a long-acting injectable testosterone for the treatment of male hypogonadism.

Over the last six decades, tremendous strides have been made in the development of safe, efficacious and 'patient-friendly' modalities of testosterone replacement therapy in men. The most recent forms of androgen replacement that are in widespread use include testosterone patch and gel. These preparations are convenient in their use and deliver a physiological amount of testosterone. Although these transdermal preparations are gaining popularity, many hypogonadal men still receive treatment with intramuscular esters. Testosterone enanthate remains the most commonly prescribed ester. Although testosterone esters are efficacious in terms of improving bone and muscle mass, they possess unfavourable pharmacokinetics that result in fluctuations in the mood, energy and sexual function of patients. Furthermore, these esters need to be injected every 2-4 weeks. Hence, there has been a need to develop long-acting esters that can be administered infrequently and deliver a physiological amount of testosterone without major fluctuations. Recently, injectable testosterone undecanoate (Nebido) has become available in Europe and will soon be marketed in south America, Asia and Australia. In this paper, the structure, pharmacokinetics, efficacy and side-effect profile of testosterone undecanoate will be reviewed and also compared with other existing testosterone esters.

Delayed-Action Preparations↗
PubMed1993

Transdermal nicotine substitution: pharmacokinetics of nicotine and cotinine.

The use of tobacco has resulted in major health related problems worldwide. Nicotine replacement is one of the most promising strategies in smoking cessation. The in vivo delivery rate and the pharmacokinetic properties of a recently developed transdermal nicotine system (TNS) was investigated in three separate studies. Two sizes (16 cm2 and 24 cm2) of the patches were tested. Mean daily nicotine delivery, expressed by a first order kinetic, varied between 0.9 and 1.0 mg/cm2 patch. The different sizes of the patches led to linearly dose-related nicotine plasma Cmax- and AUC-values. The nicotine levels achieved were in the same range with those of other nicotine patches and the chewing gum. As a result of multiple dose kinetic, no significant accumulation of nicotine was observed. Mean elimination half-life of nicotine after removal of the patches (3.5 +/- 1.8 h for the larger patch and 4.5 +/- 1.9 h for the smaller patch) was longer than reported values after i.v. administration, which was reported to vary between 40 and 120 min.

Administration, Cutaneous↗
PubMed1995

Pharmacist counseling and outcomes of smoking cessation.

The Pharmacists Educating Patients Program (PEPP) was designed (1) to provide pharmacists with smoking cessation consultation guidelines for patients on nicotine transdermal therapy and (2) to test the effectiveness of these pharmacists' consultation services. More than 6,500 pharmacies and 40,220 patients participated in this program. One year after treatment began, a survey of 2,001 patients on nicotine transdermal therapy found that those who had not joined a comprehensive smoking cessation program (86.5%) but were counseled by a pharmacist had a self-reported smoking cessation rate of 37% at the end of treatment, and 33% at an average of 10 months after treatment. The average length of treatment was five weeks. Patients who participated in a comprehensive behavioral smoking cessation program, such as SmokEnders, and who also received counseling from their pharmacists (13.5% of surveyed patients) had a quit rate of 62% at the end of treatment and 45% after 10 months. Among surveyed patients, those who stopped smoking reported that their pharmacists' counseling had been more intense and more helpful than the counseling reported by those who did not stop smoking. In addition, those who stopped smoking had more pharmacist counseling interventions and more weeks on nicotine patch treatment than did those who failed to stop smoking. Results of this study show that pharmacists who counsel patients on nicotine transdermal therapy about smoking cessation can improve outcomes.

Administration, Cutaneous↗
PubMed2002

17beta-estradiol matrixpatch removal and reapplication in postmenopausal women: theoretical predictions with an oscillating diffusion coefficient model.

The pharmacokinetic performance of a matrix system for transdermal beta-estradiol (E(2)) delivery after multiple consecutive dosing in postmenopausal women undergoing hormone replacement therapy was investigated. The E(2) plasma profiles determined during the third application in 16 postmenopausal women were compared with results obtained in a published clinical study using the same patch in 24 postmenopausal women without E(2) pretreatment; they were compared with a theoretical diffusion/pharmacokinetic model. A conventional theoretical model with constant model parameter (CPM) obtained from in vitro mass balance experiments in a Franz cell type set up described successfully the transdermal E(2) bioavailability parameter AUC(0-96h) (4341.9 +/- 1513.1; calculated 4250.8) and C(average) (45.0 +/- 13.2; calculated 41.2). Also, experimentally, there was no significant drop in E(2) plasma values after patch removal and reapplication; this was corroborated by calculations. Accumulation of E(2) did not occur when several patches were applied consecutively over a period of 3 weeks. Steady state was achieved following application of the first patch. However, the differences between recorded E(2) plasma profiles and theoretical results detected at specific measurement points cannot be explained by the CPM model. Experimentally obtained plasma profiles were always lower in the morning and higher in the evening than predicted on the basis of the model. Measurements of in vivo skin temperature in the postmenopausal women showed oscillating temperature profiles in the form of a cosinor function: The temperature mesor of untreated postmenopausal women was 34.8 degrees C with an acrophase at 17.0 o'clock (95% CI: 14.30-19.30) and an amplitude of +/- 0.4 degrees C (p = 0.1). During the application of the patch the average temperature next to a patch rose 0.3 degrees C, which was statistically significant (p = 0.1). In the skin under the application of the matrix patch a mesor temperature was detected as 35.6 degrees C with an amplitude of +/- 0.5 degrees C with an acrophase at 17.51 o'clock (95% CI: 14.30-21.00) (p = 0.05). The temperature period was 24 h for all measurements and the maximum temperature was observed at about 16.30 h, and a minimum at about 5.00 h. A linear dependency was detected in in vitro experiments between the log of E(2) permeability and the temperature for stripped skin, epidermis/dermis layer, as well as for the matrix. Modeling of E(2) plasma profiles with oscillating diffusion coefficients (ODM1) with a sine wave function results in this equation: D(1) = D(0x) + Da(x).sin(k.t). D(0x) is the diffusion coefficient determined at 35.6 degrees C, k is 1/24 h, D(a) is the diffusion coefficient of the temperature amplitude, h is hour, and x stands for the respective diffusion layer. It was shown that the experimental E(2) plasma profile variations are more pronounced than can simply be explained by skin temperature variations alone (ODM1 model). A simplex fit with an oscillating diffusion coefficient in the form of a sine wave function for the stratum corneum (ODM2 model) resulted in a temperature amplitude of 1.1 degrees C, about twice as high as was determined in the in vivo measurements (ODM2 model). Therefore, other circadian parameterlike blood flow might superimpose the temperature profile. The improvement in data analysis by incorporating oscillating diffusion coefficients (ODM1 and 2) over CPM was judged from a comparison of experimental data with the calculated plasma profiles with the AIC, Akaikes model selection criterion, which allows ranking between models because it is independent of the scaling of the data points. ODM1 and ODM2 improved the data analysis over CPM by allowing better calculation of experimental C(max), t(max), the time to reach to C(max), and the fluctuation, f. No difference between CPM, ODM1, or ODM2 was found for the bioavailability parameter C(average) and AUC(0-96h).

Administration, Cutaneous↗
PubMed2006

Transdermal nicotine for smoking cessation in postmenopausal women.

This study examined the efficacy of transdermal nicotine in postmenopausal smokers, and whether a history of depression or hormone replacement therapy (HRT) moderated smoking cessation outcomes. Postmenopausal smokers (N=152) received intensive smoking cessation counseling and were randomly assigned to use either a 21-mg nicotine patch for 3 months, with a 1-month taper, or a placebo patch. The primary outcome was biochemically validated 7-day point prevalence smoking abstinence during treatment (i.e., 1, 2, 6, and 12 weeks after the quit date) and 1 year after study medication was discontinued. Subjects who received transdermal nicotine were significantly more likely than placebo-treated subjects to remain abstinent from smoking during treatment, but not at the 1-year follow-up. The majority of subjects (>50%) in both groups accurately identified their treatment assignment. History of depression was associated with a decreased likelihood to abstain from smoking throughout the study. HRT did not moderate smoking outcomes. These data indicate that transdermal nicotine may provide short-term benefits for smoking cessation in postmenopausal women. However, efforts are needed to improve long-term abstinence rates and smoking outcomes among women with a history of depression.

Administration, Cutaneous↗
PubMed1997

Preliminary evaluation of primaquine activity on rodent malaria model after transdermal administration.

The aim of this preliminary study was to investigate the potential use of the transdermal route for primaquine administration in the treatment of malaria. Thus the activity of this drug on asexual blood forms of two rodent malaria parasites (P. v. petteri and P. y. nigeriensis) was evaluated following a single TTS patch application. Sustained plasma concentration values were observed for about 60 hours. The results obtained from a prepatency test showed that primaquine was more active towards P. v. petteri than P. y. nigeriensis. This preliminary study showed that the transdermal route for primaquine administration may be a promising strategy for improving the treatment of malaria in both causal prophylactic and prevention of relapses infection.

Administration, Cutaneous↗
PubMed2000

Pharmacokinetics of transdermal fentanyl in the peri-operative period in young children.

The pharmacokinetics of transdermal fentanyl were assessed in eight children aged 18-60 months, weighing 11-20 kg and monitored postoperatively in the intensive care unit. A patch, delivering 25 microg.h-1 of fentanyl, was applied for 72 h from the induction of anaesthesia. Plasma fentanyl concentrations were measured over 144 h. Mean (SD) peak concentration of fentanyl was 1.7 (0.66) ng.ml-1 and time to reach maximal plasma concentration was 18 (11) h. The elimination half-life was 14.5 (6.2) h, and the area under the curve for plasma fentanyl concentration (0-144 h) was 86.8 (27) ng.h.ml-1. Maximal fentanyl concentration was negatively correlated with patient age (r = - 0.71; p = 0.049) but not with body weight. These results suggest that the pharmacokinetics of transdermal fentanyl in children are similar to those in adults.

Administration, Cutaneous↗
PubMed1992

Transdermal nitroglycerin efficacy in patients with chronic stable angina pectoris as related to sympathetic and renin-angiotensin-aldosterone activity.

The aim of this study was to evaluate the acute effects of transdermal nitroglycerin on the sympathetic and renin-angiotensin-aldosterone systems activity, in a group of patients with stable exercise induced angina pectoris. Eighteen outpatients (15M, 3F, age range 47-65 years) were included in this double-blind, randomized, crossover trial comparing the antianginal effects of a transdermal system delivering 20 mg.day-1 of nitroglycerin to an identical placebo. Plasma renin activity, plasma aldosterone and catecholamine concentrations were measured in resting basal conditions and at 4, 8, 24, and 32 h post-dosing. Patients were subdivided in two groups according to the increase in exercise duration after patch application greater than 30% (responders, n = 8) and less or equal to 30% (non-responders, n = 10) in respect to placebo. In responders plasma norepinephrine was slightly increased during transdermal nitroglycerin administration in comparison to placebo while no change was observed in plasma adrenaline and aldosterone concentrations and in plasma renin activity. In non-responders plasma norepinephrine levels significantly increased during nitroglycerin treatment in comparison with placebo. Multiple comparisons showed that this increase was significant at 4, 8 and 24 h post-dosing. Plasma epinephrine and aldosterone concentrations and plasma renin activity were also increased after nitroglycerin administration. In the population as a whole, a significant inverse correlation was found between the percent increase in exercise duration (active drug vs placebo) and the absolute values of plasma norepinephrine and aldosterone, 4 h post-dosing.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Cutaneous↗
PubMed2001

Treatment of chronic hypertension with intravenous enalaprilat and transdermal clonidine.

We report an 11-year-old boy with hypertension and chronic intestinal pseudo-obstruction, which renders him totally dependent on parenteral nutrition and prevents the use of oral medications. Here we report the feasibility of utilizing chronic i.v. enalaprilat and transdermal clonidine on a chronic basis to control hypertension. Over the last 10 months, the patient's hypertension has been well controlled by 1.25 mg i.v. enalaprilat every 8 h and a 0.2-mg clonidine patch every 6 days, with no apparent side-effects. There are no reports of i.v. enalaprilat usage exceeding 3 weeks' duration. Therefore we believe that it is possible to effect reasonable management of chronic hypertension with the use of chronic i.v. enalaprilat and transdermal clonidine therapy.

Administration, Cutaneous↗
PubMed1985

Efficacy of transdermal glyceryl trinitrate in the treatment of chronic stable angina pectoris.

A study was carried out to assess the efficacy of a new transdermal preparation of glyceryl trinitrate (Transiderm-Nitro 5) in the 24 hour prophylaxis of angina and to determine the duration of effect of a single patch application. Twelve men with chronic stable angina were studied in a randomised, placebo controlled, double blind trial. By serial treadmill exercise testing a therapeutic effect was shown at three hours; the exercise time to angina and to 1 mm ST segment depression and the total exercise time were all significantly increased. At 24, 48, and 72 hours, however, no therapeutic effect was observed. Recent studies have shown a similar lack of effect at 24 hours for various forms of transdermal delivery systems. It is suggested that this lack of effect is due to the rapid onset of tolerance probably as a result of the constancy of blood concentrations obtained by this method of administration.

Administration, Topical↗
PubMed1999

Percutaneous absorption of progesterone in postmenopausal women treated with transdermal estrogen.

OBJECTIVE: The objective of this study was to evaluate the serum levels of progesterone resulting from the application of a progesterone cream to the skin. STUDY DESIGN: Six postmenopausal women were evaluated at a university clinic over a 4-week period. RESULTS: Transdermal estradiol 0.05 mg was applied 2 days before the first application of progesterone (30 mg/d) and was continued throughout the study. Patches were changed twice a week. Progesterone cream was applied once a day for 2 weeks. On day 15 and for the next 2 weeks, the progesterone cream was applied twice daily (60 mg/d). Serum 17beta-estradiol and progesterone were measured at 9 different times over a 24-hour period on day 1 and at weekly intervals for the 4-week duration of the study. Serum 17beta-estradiol concentrations varied among women, with mean concentrations of 40 to 64 pg/mL observed. Consistency in 17beta-estradiol concentrations was found within individual persons throughout the study. Serum progesterone concentrations also varied among women, with mean concentrations ranging from 1.6 to 3.3 ng/mL. After 2 weeks of percutaneous dosing, progesterone concentrations were sustained for at least 8 hours and were consistent within a given person. An appropriate increase in progesterone concentration occurred after 4 weeks compared with 2 weeks of application. Individually, a 0.53 correlation, significant at P <.0001, was seen between the absorption of 17beta-estradiol and progesterone. CONCLUSION: Significant increases in serum concentrations of progesterone were observed in all of the women studied. The percutaneous absorption of progesterone correlates strongly with the absorption of transdermal 17beta-estradiol. There is variance in absorption of progesterone just as with 17beta-estradiol, and the 2 measures are closely correlated. The percutaneous application of progesterone cream appears to be a safe and effective route of administration.

Administration, Cutaneous↗