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PubMed1993

Evaluation of local anesthesia provided by transdermal patches containing different formulations of tetracaine.

Topical formulations of tetracaine in vehicles of propylene glycol and saline are tested on human volunteers with standard occlusive, adhesive, transdermal patches. The effects of formulation composition, dose, and onset time are investigated. Dose-response studies indicate that the optimum formulation for the diffusion of tetracaine in vivo is 60% free base and 40% acid salt (w/w) in 40% propylene glycol and 60% saline (v/v). A concentration of 0.3 M [8.3% (w/v)] tetracaine is sufficient to reach the dose plateau. Time-response studies indicate that high concentrations of tetracaine in the optimum formulation [1.1 and 1.8 M, 30 and 50% (w/v), respectively] can produce statistically significant analgesia relative to a placebo after 45 min. Comparison of these in vivo data with earlier in vitro data indicate that the optimum formulation with regard to clinical studies is identical to that for in vitro diffusion through hairless mouse skin [60% free base and 40% acid salt (w/w) in 40% propylene glycol and 60% saline].

Administration, Cutaneous↗
PubMed2005

Comparison of ethinylestradiol pharmacokinetics in three hormonal contraceptive formulations: the vaginal ring, the transdermal patch and an oral contraceptive.

This open-label, randomized study compared the pharmacokinetics of ethinylestradiol (EE) from the contraceptive vaginal ring NuvaRing (15 microg EE/day), the transdermal patch (20 microg EE/day) and a combined oral contraceptive (COC) containing 30 microg EE. After 2-8 weeks of synchronization by COC treatment, subjects were randomized to 21 days of treatment with NuvaRing, patch or COC. Analysis of area under the EE concentration-versus-time curve (AUC) during 21 days of treatment showed that exposure to EE in the NuvaRing group was 3.4 times lower than in the patch group (p < .05) and 2.1 times lower than in the pill group (p < .05). Serum EE levels of subjects showed much lower variation with NuvaRing than with the patch or the COC. Thus, exposure to EE was significantly lower with NuvaRing than with the patch and pill methods, demonstrating that NuvaRing is a low-estrogen-dose contraceptive method that also results in low estrogen exposure.

Administration, Cutaneous↗
PubMedDate not supplied

Transdermal patch delivery of acetylcholinesterase inhibitors.

Transdermal delivery of cholinesterase inhibitors (ChEI) for treatment of dementia would have advantages associated with continuous dosing and enhanced compliance, but feasibility depends on achieving desired levels of central nervous system enzyme inhibition. We developed a patch technique for assessing delivery of ChEI in rats and examined two organophosphate compounds, metrifonate and DDVP, and a carbamate, heptylphysostigmine, for production of peripheral and central nervous system ChE inhibition at target levels. With DDVP, a log-dose/percent brain AChE inhibition was obtained over a range of 10-65% inhibition within a 10-fold concentration of inhibitor in the patch. Brain cholinesterase was inhibited up to seven days after a 24-h patch application. Long-term inhibition was greater than that attained after intramuscular injection, but without the rapid initial inhibition peak seen with the latter route. In contrast to DDVP, sustained high levels of brain enzyme inhibition could not be produced by transdermal delivery of metrifonate or heptylphysostigmine. Apparently DDVP has features, i.e., liquid state in pure form and high inhibitor potency, which make it particularly suitable for patch administration.

Acetylcholinesterase↗
PubMedDate not supplied

The cost-effectiveness of the nicotine transdermal patch for smoking cessation.

BACKGROUND: Smoking is the single most preventable cause of premature mortality in the United States. In 13 double-blind, controlled trials, the nicotine transdermal patch has been demonstrated to be an effective aid to quitting smoking, even after 6 months of follow-up. Because physicians and payers may consider the cost of the patch to be prohibitive, we examine the cost-effectiveness of the nicotine patch as an adjunct to brief physician counseling during routine office visits. METHODS: We estimate the effectiveness of both patch use with brief counseling and counseling alone from meta-analysis of clinical trials. Benefits are measured in terms of years of life gained by those who quit, discounted at 5%. Costs include physician time and patch prescriptions. The incremental cost-effectiveness is quantified as cost per additional year of life saved when patch plus counseling is compared with brief physician counseling alone. RESULTS: Depending on age, the average costs per year of life saved range from $965 to $1,585 for men and from $1,634 to $2,360 for women. Incremental costs per year of life saved range from $1,796 to $2,949 for men and from $3,040 to $4,391 for women. CONCLUSION: The nicotine patch is cost-effective and less costly per year of life saved than other widely accepted medical practices. Physicians and third-party payers should recommend the nicotine patch to patients who wish to stop smoking.

Administration, Cutaneous↗
PubMed1997

Pharmacokinetics of estradiol and of estrone during application of three strengths of an estradiol transdermal patch with active matrix.

The pharmacokinetic pattern of estradiol (CAS 50-28-2) and of estrone (CAS 53-16-7) during and after application of three strengths of a new transdermal estradiol patch (Dermestril) with active matrix was investigated in a cross-over study in 24 women in natural or surgical menopause. Free estradiol and estrone were assayed by GC-MS on plasma samples obtained during a 4-day application on the upper buttocks of the patches with 3 strengths and release rates of 25, 50 and 100 micrograms/day estradiol. The estradiol concentrations in plasma increased from 0-10 pg/ml typical of menopause to average concentrations of 23, 40 and 79 pg/ml during the application of the new estradiol transdermal patches with the three strengths. The concentrations of estradiol are in the range of those during the early follicular phase in women in fertile age. The increases were linearly related with the strength of the patches. Upon removal of the patches the estradiol concentrations returned to the basal low values in 8-24 h. Retarded with regard to estradiol, there was also an increase of estrone, from basal average concentrations of 22-32 pg/ml up to 31, 39 and 60 pg/ml. The increase of estrone was less pronounced than that of estradiol. Also estrone returned to its basal concentrations 24 h after removal of the patches. The estradiol/ estrone ratio from very low values typical of postmenopause increased to values of about 1, i.e. in the range of those found during the fertile age of woman. The adhesion of the patches was satisfying, provided that direct rough frictions were avoided. The patches were locally well tolerated, with rare mild and transient irritating effects on the skin. Also the systemic tolerability was good, with occasional mild or moderate side effects typical of estradiol (headache, mastodynia and pelvic heaviness) which in the practical use can be easily avoided by the application of patches of lower strength.

Administration, Cutaneous↗
PubMed2000

Duragesic transdermal patch: postmortem tissue distribution of fentanyl in 25 cases.

Fentanyl is a potent, short-acting narcotic analgesic widely used as a surgical anesthetic and for the control of pain when administered in the form of a transdermal patch. The success of the patch can be attributed to fentanyl's low molecular weight and its highly lipophilic nature, which enables it to be readily absorbed through the skin and subsequently distributed throughout the body. Over the past three years, the Los Angeles County Coroner's Toxicology Laboratory has encountered 25 cases involving Duragesic patches (fentanyl), and their postmortem tissue distributions are presented here. The analysis of fentanyl from postmortem specimens (3-mL or g sample size) consisted of an n-butyl chloride basic extraction followed by identification and quantitation on a gas chromatograph-mass spectrometer using the selected ion monitoring (SIM) mode. The fentanyl ions monitored were m/z 245, 146, and 189 and the internal standard, fentanyl-d5 ions, were m/z 250, 151, and 194 (quantitation ion underlined). The linear range of the assay was 1.67 microg/L to 500 microg/L with the limit of quantitation and detection of 1.67 microg/L. The postmortem tissue distribution ranges of fentanyl in the 25 fatalities were as follows: heart blood, 1.8-139 microg/L (23 cases); femoral blood, 3.1-43 microg/L (13 cases); vitreous, +<2.0-20 microg/L (4 cases); liver, 5.8-613 microg/kg (22 cases); bile, 3.5-262 microg/L (15 cases); urine, 2.9-895 microg/L (19 cases); gastric, 0-1200 microg total (17 cases); spleen, 7.8-79 microg/kg (3 cases); kidney, 11 microg/kg (1 case); and lung, 31 microg/kg (1 case). The age of the decedents in this study ranged from 19 to 84, with an average age of 46. The modes of death included 15 accidental, 5 natural, 3 suicidal, and 2 undetermined. The main objectives of this paper are to show the prevalence of fentanyl patches in our community and to aid the forensic toxicologist with the interpretation of postmortem fentanyl levels in casework.

Administration, Cutaneous↗
PubMed2005

A pilot study of an investigational testosterone transdermal patch system in young women with spontaneous premature ovarian failure.

CONTEXT: Evidence suggests that young women with spontaneous premature ovarian failure (sPOF) have significantly lower androgen levels than age-matched regularly menstruating women. OBJECTIVE: The objective of the study was to evaluate an investigational testosterone transdermal patch (TTP) designed to deliver the normal ovarian production rate of testosterone. DESIGN: This was an open-label study (2-month baseline period followed by 2-month treatment period). PATIENTS: Nine women with sPOF and a history of regular bleeding patterns on standard estrogen/progestogen cyclic treatment participated in the study. One subject with abnormal baseline levels was excluded. INTERVENTION: Four consecutive 28-d cycles of transdermal estradiol (E2; 0.1 mg/d) and sequential oral medroxyprogesterone acetate (MPA; 10 mg/d for the last 12 d of each cycle). During cycles 3 and 4, an investigational TTP (nominal delivery 150 microg/d) was applied twice weekly to the abdomen. MAIN OUTCOME MEASURES: Steady-state pharmacokinetic profiles of free and total testosterone and scheduled vaginal bleeding patterns were studied. RESULTS: The mean (95% confidence interval) of the time-average free testosterone levels during TTP treatment was 7.5 (4.9-9.9) pg/ml; 26.0 (17.2-34.6) pmol/liter (with E2), and 6.9 (4.9-8.8) pg/ml; 23.9 (17.2-30.5) pmol/liter (with E2 and MPA). The confidence intervals of the means include the upper limit of normal for premenopausal women, i.e. 6.8 pg/ml (23.5 pmol/liter), although the mean values are slightly above this. CONCLUSIONS: The addition of TTP to cyclic E2/MPA therapy in women with sPOF produced mean free testosterone levels that approximate the upper limit of normal. A 3-yr study to assess safety and effectiveness in this population is in progress.

Administration, Cutaneous↗
PubMed1999

Randomized comparative trial of nicotine polacrilex, a transdermal patch, nasal spray, and an inhaler.

BACKGROUND: There are several nicotine replacement products on the market, and physicians are likely to be asked with increasing frequency about which of these products their patients should use. OBJECTIVE: To provide a basis for rational advice by comparing nicotine polacrilex (gum), a transdermal patch, nasal spray, and an inhaler. DESIGN: Randomized trial with assessments at the quit date and 1, 4, and 12 weeks later. SETTING: Hospital smokers' clinic. PATIENTS: Male and female community volunteers (N = 504) smoking 10 or more cigarettes per day and seeking help to stop smoking. INTERVENTIONS: Patients were given brief advice, and purchased their nicotine replacement treatment at approximately half the regular retail price. MAIN OUTCOME MEASURES: Nicotine replacement treatment use, ratings of withdrawal symptoms, ratings of product characteristics and helpfulness, and biochemically validated continuous lapse-free abstinence. RESULTS: The products did not differ in their effects on withdrawal discomfort, urges to smoke, or rates of abstinence. The continuous validated 12-week abstinence rates were 20%, 21%, 24%, and 24% in the gum, patch, spray, and inhaler groups, respectively. Compliance with recommended nicotine replacement treatment use was high for the patch, low for gum, and very low for the spray and the inhaler. The spray was underused because of adverse effects more often than the other products. In the subjects using the spray, the level of use among abstainers at week 1 predicted outcome at week 12. The inhaler was rated as more embarrassing to use than the other products, but provided at least as much nicotine as the gum. CONCLUSION: When asked about nicotine replacement treatment products available, physicians should note that, despite low compliance with the recommended dose of the spray and inhaler and differences in product ratings, overall, there are no notable differences between the products in their effects on withdrawal discomfort, perceived helpfulness, or general efficacy.

Administration, Cutaneous↗
PubMed2000

Bioavailability and pharmacokinetic profile of glyceryl trinitrate and of glyceryl dinitrates during application of a new glyceryl trinitrate transdermal patch.

The pharmacokinetics and bioavailability of glyceryl trinitrate (GTN, CAS 55-63-0) and of its main metabolites, i.e. 1,2-glyceryl dinitrate (1,2-GDN, CAS 621-65-8) and 1,3-glyceryl dinitrate (1,3-GDN, CAS 623-87-0), were compared during a single 24-h application of a new GTN transdermal patch (Epinitril 10, hereinafter called EPI-10) or a reference patch (hereinafter called ND-10) releasing 10 mg GTN in 24 h. The study was an open, randomized balanced cross-over study on 24 healthy male volunteers to whom the patches were applied to the antero-lateral part of the thorax in two periods separated by a 3-day wash-out. Blood samples were collected before administration, during the 24-h patch application and at 0.5, 2 and 3 h after patch removal. Assayed in plasma were GTN, 1,2-GDN and 1,3-GDN using validated GC/MS methods with stable isotope-labeled internal standards (15N3-GTN, 15N2-1,2-GDN, and 15N2-1,3-GDN). The ratios of the AUCs of GTN, 1,2-GDN and 1,3-GDN measured during application of EPI-10 or of ND-10 were within the 0.85-1.25 limits required to assess equivalence of the extent of bioavailability. The ratios of the Cmax were within said limits for the signal metabolite 1,2-GDN and only slightly below (0.78-1.16) for the parent GTN. EPI-10 can therefore be considered equivalent to ND-10 also with regard to the rate of bioavailability. Under both patches GTN reached steady-state levels after 3-6 h of patch application and remained on sustained levels during the whole 24-h application. The plasma levels of 1,2-GDN were about 6 times higher than those of GTN. The plasma levels of 1,3-GDN were similar to those of GTN. Upon removal of the patches the concentrations of the three nitrates fell to negligible values within 3 h. Both patches were well tolerated at the application site. For its small size, thinness and transparency, EPI-10 is very patient friendly, a quality that improves compliance with the therapeutic regimen.

Adhesiveness↗
PubMed2006

The vaginal ring and transdermal patch: new methods of contraception.

The most common method of reversible contraception used worldwide is the intrauterine device. However, in the Asia-Pacific the combined oral contraceptive pill and condoms, methods of contraception that require a high degree of day-to-day user compliance, are more popular. The combined vaginal ring and transdermal patch have been developed to overcome the need for daily compliance associated with combined pill use. They have the added advantages of non-oral delivery, thus avoiding gastro-intestinal interference with absorption, and in addition there is no hepatic first-pass effect. Both have been available internationally for some years and offer an alternative to the combined pill. This article reviews and summarises published data on these new methods.

Administration, Cutaneous↗
PubMed2000

Plasma levels of glyceryl trinitrate and dinitrates during application of three strengths of a new glyceryl trinitrate transdermal patch.

The pharmacokinetic characteristics and the bioavailability of glyceryl trinitrate (GTN, CAS 55-63-0) and of its main metabolities 1,2-glyceryl dinitrate (1,2-GDN, CAS 621-65-8) and 1,3-glyceryl dinitrate (1,3-GDN, CAS 623-87-0) during a single 24-h application of three strengths of a newly developed GTN transdermal patch (Epinitril) were investigated. The three strengths coded in this paper EPI-5, EPI-10 and EPI-15 have a nominal release rate of GTN of 5, 10 and 15 mg, respectively, in 24 h. The study was an open, randomized balanced cross-over study on 18 healthy male volunteers, to whom the patches were applied for 24 h to the antero-lateral part of the thorax in three periods, separated by an at least 3-day wash-out. Blood samples were collected before administration, during the 24-h patch application and 1, 3 and 6 h after patch removal. Assayed in plasma were GTN, 1,2-GDN and 1,3-GDN using validated GC/MS methods with stable isotope labeled internal standards (15N3-GTN, 15N2-1,2-GDN, and 15N2-1,3-GDN). GTN and its two metabolites reached the plateau already 3 h after application of the patches and remained on extended and fairly constant levels during the whole 24-h application. The plasma levels of the three nitrates were proportional to the strengths of the patches. The plasma levels of 1,2-GDN were about 6 times higher than those of GTN. The plasma levels of 1,3-GDN were similar to those of GTN. Upon removal of the patches the concentrations of the three nitrates fell to negligible values within 3 h, an important property when an intermittent GTN therapy is needed in order to avoid tolerance to the drug. The patches were well tolerated at the application site. For their good tolerability, small size and transparency, the new GTN patches are very patient friendly, a quality that improves compliance with the therapeutic regimen.

Adhesiveness↗
PubMed1996

Development of a transdermal patch of methadone: in vitro evaluation across hairless mouse and human cadaver skin.

A 3-day monolithic polyacrylate adhesive dispersion type delivery system containing methadone was fabricated and in vitro permeation through hairless mouse and human cadaver skins was conducted. The effect of skin permeation enhancers was also investigated. Skin permeation rate across human cadaver skin was found to be lower than that of hairless mouse. Skin permeation profiles across both types of skins showed a membrane permeation controlled cumulative amount permeated (Q) versus time (t) relationship. Skin permeation rate was found to be dependent on both adhesive film thickness and loading dose of the drug in the matrix. Effective skin permeation rate across the hairless mouse skin was obtained from a patch with 1.5 mm thickness and 15% w/w loading dose. n-Decylmethyl sulfoxide and Azone were found to produce an effective skin permeation rate of methadone through human cadaver skin at a 5% w/w concentration. These initial studies demonstrated the feasibility of methadone administration through intact skin from a transdermal patch.

Administration, Cutaneous↗
PubMed2001

Evaluation of fentanyl transdermal patches in rabbits: blood concentrations and physiologic response.

In the study reported here, we sought to evaluate transdermal fentanyl patches for their ability to achieve detectable plasma concentrations with minimal adverse effects in New Zealand White rabbits. Fentanyl patches were applied to the dorsum after removing hair either by clipping or by application of a depilatory agent. Blood samples were collected every 12 h for a total of 96 h (24 h after patch removal) for determination of plasma fentanyl concentration. At those times, rabbits were assessed for changes in body temperature, heart rate, respiratory rate, and body weight. In rabbits with clipped hair, where rapid hair re-growth was not a mitigating factor, mean plasma fentanyl concentration reached a mean (+/- SEM) peak of 1.11 +/- 0.32 ng/ml at 24 h, decreased to 0.77 +/- 0.21 ng/ml at 72 h, and was negligible at 96 h. In rabbits with depilated hair, peak concentration was obtained at 12 h (6.7 +/- 0.57 ng/ml) and decreased gradually to 0.27 +/- 0.06 ng/ml at 72 h. In a second group of fentanyl-treated rabbits in which hair started growing back within 24 h, plasma fentanyl concentration was not detectable. Control and fentanyl-treated rabbits with clipped hair had no effect from the experimental manipulations other than slight loss in body weight. In the depilatory group, two rabbits appeared moderately sedated during the initial 12-h period, and had decreased respiratory rate for 24 h. In conclusion, rabbits tolerate the transdermal fentanyl patch well. Hair regrowth in rabbits may present a complicating factor that impedes dermal absorption of fentanyl. The application of a depilatory agent lead to early and rapid absorption of fentanyl causing undue sedation in some rabbits and lack of sustained plasma concentrations for the desired three-day period.

Administration, Cutaneous↗
PubMed2000

Permeation studies comparing cobra skin with human skin using nicotine transdermal patches.

Cobra skin (Naja Naja Khaotia) was used as a barrier for an in vitro permeation study using nicotine. Fluxes of nicotine that permeated from Nicotinell through cobra skin (CS) taken from the head, body, and tail were 233.93 +/- 16.08, 206.87 +/- 19.00, and 211.26 +/- 22.93 micrograms/cm2/hr1/2, respectively (n = 6). This indicated no significant difference (p > .05). Abdominal human epidermis (HE), obtained from cadavers, and the CS provided identical permeation kinetics for nicotine, which can be described by Mt = 4M alpha (Dt/pi L2)1/2. The mean flux of nicotine formulated as an acrylic transdermal patch that permeated through HE was 137.92 +/- 67.79 micrograms/cm2/hr1/2 (4 specimens, n = 12), whereas that through CS was 180.13 +/- 41.05 micrograms/cm2/hr1/2 (4 specimens, n = 15). The ratio of the fluxes of nicotine from formulated patches having three different nicotine contents using CS and HE was 1.22 to 1, respectively, for each of the patches irrespective of nicotine content. The coefficients of variation of the nicotine permeated were 22.79% and 49.15% for CS and HE, respectively, that is, a narrower variation of results was obtained with CS. This indicated that CS could be used for nicotine permeation studies.

Administration, Cutaneous↗
PubMedDate not supplied

Changes in compulsion and anxiety symptoms with nicotine transdermal patches in non-smoking obsessive-compulsive disorder patients.

OBJECTIVE: Some of the obsessive-compulsive disorder (OCD) symptoms can be elicited in rats by the administration of quinpirole (D2/D3 dopaminergic agonist). Nicotine administration blocked some aspect of checking behavior in that model. The main goal of this study was to determine if the clinical manifestations of OCD non smoking patients change with the administration of transdermal nicotine patches. MATERIAL AND METHODS: Eleven patients were studied (6 female and 5 males), average age 29.7 +/- 5.5 years. All of them were OCD according to DSM-IV criteria. Clinical scorings were done with Yale-Brown Obsessive Compulsive Scale (Y-BOCS), Beck Depression Inventory (BDI) and Beck Anxiety Inventory (BAI). Nicotine (17.5 mg/day) or placebo transdermal patches were randomly administered for five continuous days. RESULTS: Nicotine administration reduced the total Y-BOCS and the compulsive score of that scale, but did not reduce obsessions. Also anxiety was reduced as was shown by the BAI scores, when patients were on nicotine patches, no changes were observed in BDI. CONCLUSIONS: The present results replicated the animal findings about reduction in compulsive behavior after nicotine administration. Also suggest that nicotine depending on the dysfunction of the different neurotransmitter systems may produce different behavior or cognitive effects, also that even nicotine showed some beneficial effect in OCD patients, the low rate of nicotine smoking in this type of patients, may show other mechanisms than may protect to smoke in some psychiatric patients.

Administration, Cutaneous↗
PubMed2003

Nicotine applied by transdermal patch induced HSV-1 reactivation and ocular shedding in latently infected rabbits.

The identification of factors involved in herpes virus latency and reactivation is critical to a better understanding of the mechanisms essential to viral neuroinvasiveness and neurovirulence. Recurrent episodes of ocular herpes infections cause irreversible corneal scarring and are the primary cause of loss of vision due to an infectious agent in industrialized countries. In this study, we examined the ability of nicotine, a compound known to be involved in stress-associated immunomodulation and recognized as one of the most frequently used addictive agents, to induce ocular shedding in rabbits latently infected with herpes simplex virus type 1 (HSV-1) strain McKrae. New Zealand white rabbits latently infected with HSV-1 at 3-4 weeks post-inoculation were randomly divided into two groups. The corneas of all rabbits were free of lesions as verified by slit lamp biomicroscopy. One group received nicotine by transdermal patch (21 mg/day) for 20 days and the other group served as the control. Reactivation data were obtained by detection of virus in tear film collected by ocular swabbing performed concurrently with the administration of nicotine. Compilation of data from three separate experiments demonstrated that 16.5% (258/1560) of the swabs taken from rabbits treated with nicotine were positive for virus, compared with 8.3% (53/639) of swabs taken from controls. Rabbits receiving nicotine exhibited a significantly (P < 0.0001) higher rate of ocular shedding than controls. The concentration of nicotine in the serum was determined at various times (0-24 hrs) after new patch replacement. Peak (average) serum level of nicotine was obtained 8 hours after patch replacement and exhibited a broad range of values (0.233 microg/mL-6.21 microg/mL). These results suggest that an initial systemic exposure to nicotine significantly increases HSV-1 reactivation. Further studies are needed to reveal any effects of nicotine dependency and nicotine withdrawal on herpesvirus reactivation.

Administration, Cutaneous↗
PubMed2002

Simvastatin, transdermal patch, and oral estrogen-progestogen preparation in early-postmenopausal hypercholesterolemic women: a randomized, placebo-controlled clinical trial.

Hormone replacement therapy (HRT) seems to have a favorable influence on the plasma lipid profile. Only a few investigations have examined the effects of HRT versus hepatic hydroxymethyl glutaryl coenzyme A (HMG-CoA) reductase inhibitors. We compared the relative effects of different hypolipidemic strategies on lipoproteins and coagulative parameters in women with recent-onset spontaneous menopause. In this 24-week, placebo-controlled trial, 60 consecutive healthy women aged >/= 45 years, with amenorrhea from 6 to 60 months (mean, 1.9 +/- 1.4 years), serum follicle stimulating hormone (FSH) greater than 40 U/L, and slight to moderate hypercholesterolemia (low-density lipoprotein-cholesterol [LDL-C] 160 to 250 mg/dL, high-density lipoprotein-cholesterol [HDL-C] < 75 mg/dL, and triglycerides < 200 mg/dL) were enrolled and randomized to dietetic advice (placebo group), simvastatin 10 mg, 0.625 mg of conjugated equine estrogen (CEE), or 50 microg estrogen transdermal patch (ETP). In the latter 2 cases, the progestative nomegestrol was added to estrogens (days 17 to 28 of the cicle). Lipoprotein parameters were evaluated after separating very-low-density lipoproteins (VLDLs) by ultracentrifugation, while fasting glucose and insulin, homocysteine, and hemocoagulative parameters were determined in plasma. Fifty-four patients completed the trial. Total cholesterol (TC) and LDL-C significantly decrased in the simvastatin (-62 mg/dL [-20%] and -72 mg/dL [-30%], respectively), CEE (-42 mg/dL [-13%] and -45 mg/dL [-18%]), and ETP (-30 mg/dL [-10%] and -26 mg/dL [-11%]) groups compared to baseline, but only simvastatin showed an effect significantly superior to diet alone. Apolipoprotein (Apo) B was decreased by simvastatin (-25%, P <.001) and by CEE (-10%, P <.05); again, simvastatin was more effective than either diet or ETP. Triglyceride concentration and VLDL-C were unmodified by treatments. HDL-C and Apo A-I significantly increased in the simvastatin group (+18% and +8%, respectively), while HDL-C was unmodified by both HRT regimens and Apo A-I was reduced by ETP treatment (-17%); lipoprotein[a] (Lp[a]) was decreased by both HRTs (-38%, P <.05, and -22%, P =.07, for CEE and ETP, respectively). Among coagulative parameters, plasminogen activator inhibitor-1 (PAI-1) was significantly reduced by CEE (-29%, P <.05) but not ETP treatment (+16%, P = not significant), while fibrinogen, antithrombin, and homocysteine were unaffected by therapy. Thus, HRT, particularly CEE, seems well tolerated and moderately effective in improving the lipid pattern and, perhaps, the coagulative/fibrinolytic balance in postmenopausal hypercholesterolemic women; it may represent a therapeutic option in slightly dyslipidemic subjects. Statins are preferred in case of more severe disease.

Administration, Cutaneous↗
PubMed2001

Formulation and evaluation of controlled-release transdermal patches of theophylline-salbutamol sulfate.

Transdermal formulations containing theophylline and salbutamol sulfate (SS) were formulated using hydroxypropylmethylcellulose. Theophylline was loaded by adsorption with the aid of the coadsorbate sodium chloride. The formulations were subjected to in vitro release studies, and the dose of salbutamol and theophylline was optimized to yield the desired flux. The films were uniform and 93 +/- 5.4 microm thick. The in vitro fluxes of theophylline and salbutamol sulfate from the formulation were 1.22 +/- 0.4 mg/h/cm2 and 13.36 +/- 1.02 microg/h/cm2, respectively. The formulation was subjected to pharmacodynamic studies in guinea pigs. The preconvulsive time (PCT) of guinea pigs increased significantly after 4 h, and the same was observed even after 24 h Pharmacokinetic studies were carried out in healthy human volunteers. Theophylline was analyzed in saliva, and salbutamol was analyzed in the blood plasma. The Tmax of the drugs was 3 h, and appreciable concentrations of the drugs above their MEC could be analyzed even after 12 h. The elimination half-life of the drugs was significantly prolonged compared to that for tablets. There were no signs of erythema or edema in the volunteers during observation for a period of 7 days.

Absorption↗