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PubMed1992

Transdermal fentanyl: seeding trial in patients with chronic cancer pain.

In this study, 6 patients with pain from advanced cancer were enrolled in a multicenter, open-label seeding trial of transdermal fentanyl. Following equianalgesic dose conversion, transdermal fentanyl patches were applied every 3 days. Mean fentanyl dosage doubled by week 2 and tripled by week 4. Pain control improved in all patients. There were no significant changes in mood, constipation, nausea, sedation, daily activities, or interpersonal relationships from pretrial to posttrial analyses. Following the study period, 5 patients were monitored for a mean total of 55 days with a mean final fentanyl dose of 240 micrograms/hr. As part of a comprehensive cancer pain management program, transdermal fentanyl appears to be safe and effective, and should prove to be a useful addition to currently available opioid analgesics.

Administration, Cutaneous↗
PubMedDate not supplied

Quit rates at one year follow-up of Alaska Native Medical Center Tobacco Cessation Program.

The prevalence of tobacco use in the Alaska Native population is unusually high, as high as 50% in both adult men and women. In June of 1992, the Alaska Native Medical Center and the Alaska Area Native Health Service began a tobacco cessation program using behavioral modification classes and transdermal nicotine patches. Patients were subsequently followed at three month intervals for a year to assess smoking status. To date, 193 people have completed the program with at least three months having elapsed since completion of classes. The quit rates at three, six, nine, and twelve months were 31%, 30%, 24%, 21% respectively. The long-term quit rates for this tobacco cessation program are comparable to the rates of other studies which have included both behavioral modification and transdermal nicotine.

Administration, Cutaneous↗
PubMed1990

Pharmacokinetics of oral and transdermal triprolidine.

In this open, nonrandomized, three-way crossover study, six healthy male volunteers received single doses of triprolidine (TPL) hydrochloride syrup orally (2.5 mg) and wore transdermal TPL patches (5 mg and 10 mg doses) to compare the pharmacokinetic profiles and dose tolerance of the two formulations. A washout period of at least 1 week was scheduled between the three dosing periods. Blood samples were collected at defined times, and plasma concentrations were determined using a radioimmunoassay. Maximum plasma drug concentration (Cmax) decreased from 5.6 +/- 2.9 ng/mL (mean +/- SD) with oral dosing to 2.0 +/- 1.0 ng/mL and 4.2 +/- 2.0 ng/mL following 5 mg and 10 mg transdermal doses, respectively. Time to reach peak concentration (tmax) increased from 2.0 +/- 1.2 hours with oral dosing to 12.0 +/- 5.9 and 14.3 +/- 9.9 hours following 5 mg and 10 mg transdermal doses, respectively. The differences between AUC0-alpha values with the oral syrup and the 5 mg and 10 mg transdermal doses were not significant when normalized to 2.09 mg (TPL base). The bioavailabilities of the 5 mg and 10 mg transdermal doses relative to the oral 2.09 mg doses were 0.89 +/- 0.32 and 1.04 +/- 0.33, respectively. Mild erythema and pruritus were the most common adverse effects secondary to TPL transdermal application. Drowsiness observed following oral TPL, was not evident following either transdermal dose. The results of this study, therefore, indicate that TPL can be absorbed transdermally, providing consistent plasma concentrations.

Administration, Cutaneous↗
PubMed2006

Different effects of transdermal and oral hormone replacement therapy on the renin-angiotensin system, plasma bradykinin level, and blood pressure of normotensive postmenopausal women.

BACKGROUND: This study compared the efficacy of transdermally administered estradiol with that of orally administered conjugated equine estrogens (CEE) on the renin-angiotensin system, plasma bradykinin level, and blood pressure (BP) in normotensive postmenopausal women (PMW). METHODS: A total of 38 normotensive PMW were randomly assigned to two groups. The transdermal hormone replacement therapy (HRT) group consisted of 19 women treated with a continuous transdermal estradiol patch (36 microg/day) plus cyclic oral medroxyprogesterone acetate (MPA; 2.5 mg/day for 12 days) for 12 months. The oral HRT group consisted of 19 women who received continuous oral CEE (0.625 mg/day) plus cyclic oral MPA (2.5 mg/day for 12 days) for 12 months. Plasma renin activity (PRA), serum angiotensin-converting enzyme (ACE) activity, plasma angiotensin (Ang) I, Ang II, and bradykinin concentrations, and BP were measured before and 12 months after the start of HRT. RESULTS: Transdermal HRT significantly decreased both diastolic and mean BP and concomitantly reduced bradykinin levels (all P < .05). However, no significant changes in PRA, ACE activity, Ang I, or Ang II levels were observed. The BP remained unchanged in the oral HRT group, but the PRA, Ang I, Ang II, and bradykinin levels had significantly increased and ACE activity had significantly decreased (all P < .05) at 12 months after the start of HRT. CONCLUSIONS: Transdermal HRT decreased BP in normotensive PMW without influencing Ang II, whereas oral HRT increased Ang II without altering BP. Transdermal HRT may be more beneficial than oral HRT with regard to BP and Ang II levels.

Administration, Cutaneous↗
PubMed2001

Long-term effects of continuous oral and transdermal estrogen replacement therapy on sex hormone binding globulin and free testosterone levels.

OBJECTIVE: To determine the long-term effects of estrogen replacement therapy on sex hormone binding globuline (SHBG) and free testosterone (fT) levels in surgical postmenopausal women. STUDY DESIGN: Forty patients with surgical menopause were enrolled in this prospective study. The women were randomly divided into two groups. The first group received oral therapy (continuous conjugated equine estrogens (CEE) - 0.625mg per day) and the second group received transdermal therapy (patches delivering continuous 17beta-estradiol (E2)--0.05mg per day). Serum SHBG and fT levels were determined at baseline and after first and second years of treatment. Two-way repeated measures analysis of variance with Bonferroni adjusted post-hoc test and unpaired-t-test were performed for statistical analysis with SPSS program. RESULTS: Serum SHBG levels increased significantly with oral CEE after first year of treatment (P<0.05) and remained at this level for the next year. Transdermal therapy did not affect SHBG levels after first and second years (P<0.05). Serum fT levels did not change significantly in either group at the end of the first or second years (P<0.05) although there was a significant difference between the groups after 2 years (P<0.05). CONCLUSION: Oral conjugated estrogens increased SHBG levels during therapy. This effect may balance the increased estrogen and androgen stimulation on breast tissue and may be more beneficial to the cardiovascular system in postmenopausal women.

Administration, Cutaneous↗
PubMed2006

Changes in vascular flow after transdermal oestradiol therapy for prostate cancer: a mechanism for cardiovascular toxicity and benefit?

OBJECTIVE: To report the influence of transdermal oestradiol therapy on the vascular dynamics of men with advanced prostate cancer. PATIENTS AND METHODS: Twenty patients with newly diagnosed locally advanced or metastatic prostate cancer (10 each) were treated using transdermal oestradiol patches. The vascular flow was assessed 6-monthly before and during a year of therapy using arterial and venous Doppler and duplex ultrasonography, arterial and venous photoplethysmography and opto-electronic plethysmography. RESULTS: Arterial flow, as measured by the mean and peak systolic velocities and photoplethysmography, significantly increased over time. Arterial compliance initially decreased but had normalized after 12 months. The venous variables were unaffected. As a result, the total limb blood flow and the capillary filtration rate were significantly increased. CONCLUSION: Transdermal oestradiol therapy causes an increase in arterial but not venous flow, and an initial decrease in arterial compliance, which adapts to the physiological range with time. It is possible that these changes may account for the increase in cardiovascular toxicity seen in the early phase of oestrogen therapy, and the cardioprotective effect that accrues thereafter.

Administration, Cutaneous↗
PubMed1998

Plasma insulin-like growth factor-I and its binding proteins 1 and 3 during continuous nonoral and oral combined hormone replacement therapy.

OBJECTIVE: We determined the effects of continuous combined nonoral and oral estrogen-progestin therapy on plasma levels of insulin-like growth factor-I (IGF-I) and its binding proteins 1 (IGFBP-1) and 3 (IGFBP-3). DESIGN: Forty women complaining of climacteric symptoms were randomized to receive either transdermal estradiol patches (50 microg daily) in combination with an intrauterine system releasing 20 microg of levonorgestrel daily or an established regimen of an oral dose of 2 mg of estradiol and 1 mg of norethisterone acetate daily for 1 year. Fifteen women in the nonoral therapy group and 17 in the oral therapy group completed the 1-year prospective study. RESULTS: Plasma levels of IGF-I decreased significantly in the oral therapy group, but no changes were observed in the plasma levels of its binding proteins. Transdermal estrogen in combination with intrauterine levonorgestrel did not induce any change in plasma IGF-I, whereas the plasma levels of IGFBP-3 decreased. IGFBP-1 concentrations increased, which may be related to the induction of this protein into the endometrium by the intrauterine levonorgestrel delivery. CONCLUSIONS: Both the nonoral and oral continuous combined estrogen-progestin therapies used in this study produced only minor changes in the circulating concentrations of IGF-I and its binding proteins.

Administration, Cutaneous↗
PubMed1998

Application of asymmetric TPX membranes to transdermal delivery of nitroglycerin.

In this study, asymmetric poly(4-methyl-1-pentene) (TPX) membranes, fabricated by the dry/wet inversion method, were applied to transdermal delivery of nitroglycerin (NTG), a drug for treating angina pectoris. The flux of NTG through the TPX membrane was measured in vitro by a Franz cell. The results indicate that the NTG flux through asymmetric TPX membranes is strongly dependent on the membrane structure, which can be varied by adding nonsolvents in the casting solution. By adding different kinds of nonsolvents and adjusting the added amounts, membranes with different NTG release rates can be fabricated. It was also found that, with suitable drug formula, the NTG dissolution rate of a prototype TPX patch is comparable to that of a commercial patch, Transderm-Nitro. In addition, the data of NTG flux through a composite of TPX membrane and pig skin are also presented.

Animals↗
PubMedDate not supplied

Relationship between mood improvement and sleep changes with acute nicotine administration in non-smoking major depressed patients.

BACKGROUND: Acute administration of nicotine patches produced rapid eye movement sleep (REM) increases in non-smoking major depressed patients as well as clinical improvement in mood. Antidepressant effect was also observed after four continuous days of nicotine administration. The main goal of the present study was to observe the relationship between changes in REM sleep variables and mood in non-smoking major depressed patients. METHOD: Fifteen major depressed patients (DSM-III-R) were studied under the following sleep laboratory conditions: habituation, two all-night polysomnography recordings, the first one was baseline and the second one was nicotine patch (17.5 mg) night. Patients should had a HAMD-21 punctuation equal or above 18 points for to be admitted in the study. A short HAMD (10 items), and side effect scale was used daily during the two recording nights. RESULTS: A significant increase in REM sleep time and reduction in sleep stage II was observed when patients were on nicotine patches. Ten patients improved (reduction of 30% in the HAMD of 10 items), the morning after nicotine. All of them also increased REM sleep time above their baseline. Eight patients from the one with significant improvement had a short REM sleep latency below 60 minutes at baseline. CONCLUSIONS: The hypersensitivity of the cholinergic system may be related to the REM sleep enhancement effect observed in some of the patients when received nicotine and also related to the clinical improvement. The role of the acetylcholine in depression could be explored with the administration of transdermal nicotine patches.

Administration, Cutaneous↗
PubMed1993

Transdermal nitroglycerin reduces the frequency of anginal attacks but fails to prevent silent ischemia.

OBJECTIVES: The aim of this study was to objectively evaluate the effects of intermittent administration of transdermal nitroglycerin on effort tolerance, frequency of anginal attacks and presence of silent ischemic events that occur during normal daily activities. BACKGROUND: Previous studies have shown that transdermal nitroglycerin patches reduce the incidence of anginal attacks and improve exercise capacity when given intermittently. However, no carefully controlled studies are available on the effects of these preparations (and their dosing schedule) on the occurrence of "silent" ischemic events during unrestricted daily activities. METHODS: Twelve men with chronic stable angina, a positive exercise test result and significant coronary artery disease completed a randomized, double-blind, placebo-controlled trial in which patches were worn either continuously or with overnight (8 h) removal. The effects of treatment were objectively assessed by both treadmill exercise testing and 24-h ambulatory electrocardiographic monitoring. RESULTS: Only the intermittent dosing schedule afforded a small but significant improvement in exercise tolerance and prolonged exercise duration and time to ST segment depression. The frequency of anginal attacks was also reduced by both the continuous and intermittent treatment, but the effects on symptoms were not paralleled by a concomitant reduction in ischemic episodes recorded during ambulatory monitoring. CONCLUSIONS: The results indicate that when used as monotherapy, intermittent transdermal nitroglycerin preparations lessen symptoms but are ineffective for the long-term prophylaxis of silent myocardial ischemia.

Administration, Cutaneous↗
PubMed2006

Different effects of oral conjugated estrogen and transdermal estradiol on arterial stiffness and vascular inflammatory markers in postmenopausal women.

AIMS: We compared the effects of oral conjugated equine estrogen (CEE) therapy and transdermal estradiol therapy on pulse wave velocity (PWV) and circulating levels of vascular inflammatory markers in postmenopausal women and we also explored the interrelationship between the change in PWV and the changes in vascular inflammatory markers. METHODS AND RESULTS: In a randomized 12-month trial, 28 postmenopausal women received a continuous oral CEE plus cyclic medroxyprogesterone acetate (MPA), 28 received a continuous transdermal estradiol patch plus cyclic MPA, and 27 did not receive either therapy. In each subject, we measured the brachial-ankle PWV (baPWV) using an automated device, the blood pressure, and the circulating levels of vascular inflammatory markers (C-reactive protein [CRP], cell adhesion molecules [CAMs], monocyte chemoattractant protein-1 [MCP-1], and matrix metalloproteinase [MMP-9]) before and 12 months after the start of the study. Oral CEE therapy did not change the baPWV but significantly increased the CRP and MMP-9 levels (P<0.05, each) and significantly decreased the CAMs and MCP-1 levels (P<0.05, each). Transdermal estradiol therapy significantly decreased the baPWV, and the CAMs and MCP-1 levels (P<0.05, each) but had no effect on the CRP or MMP-9 levels. No significant changes were seen in the control group. The blood pressures of the subjects remained unchanged. In the transdermal estradiol group, the change in baPWV was not significantly correlated with the changes in vascular inflammatory markers. CONCLUSION: Transdermal estradiol, but not oral CEE therapy, may have antiatherosclerotic effects by improving arterial stiffness. The reduction in baPWV may contribute to the direct effect of estrogen, but not to the decrease in estrogen-induced vascular inflammatory markers.

Administration, Cutaneous↗
PubMed1987

Effects of transdermal clonidine in young and elderly patients with mild hypertension: evaluation by three noninvasive methods of blood pressure measurement.

The efficiency of the clonidine transdermal therapeutic system was assessed in a group of patients under 35 years of age and in another group of patients over 60 years of age. The patients in both groups had mild uncomplicated hypertension. Blood pressure (BP) was measured by the three following methods: by the physician; by an automatic device at the outpatient clinic; and by the patient at home. Seventeen young patients (mean age, 26 years) and 18 elderly patients (mean age, 68.5 years) were included in a double-blind crossover study comprising four periods of 2 weeks each, during which patients were given, weekly, either placebo or one and then two transdermal clonidine patches containing 2.5 mg of the drug. In the younger group, the average systolic and diastolic BPs measured by the physician after administration of two clonidine patches were, respectively, 4.9 and 5.9 mm Hg lower than after placebo (p less than 0.05). The absolute drop was more significant in the older group (9.3 and 6.0 mm Hg; p less than 0.01). In the young group, placebo markedly reduced systolic BP (9.8 mm Hg; p less than 0.01), and comparison of the three methods of BP measurement demonstrated their great reactivity to the physician's presence. Nine young and eight elderly patients received clonidine treatment for an average duration of 9 +/- 5 months. Six cases of skin reactions occurred and limited the usefulness of the clonidine transdermal system used in this study.

Administration, Cutaneous↗
PubMed1996

Effects of postmenopausal estrogen/progestin replacement therapy on LDL particles; comparison of transdermal and oral treatment regimens.

The aim of the study was to compare the effects of continuous oral estrogen/progestin therapy to the effects of transdermal estrogen therapy combined with cyclic oral progestin on the properties of LDL particles. Eighty postmenopausal women were randomly allocated to receive either oral (continuous 17-beta-estradiol 2 mg and norethisterone acetate 1 mg per day, E2/NETA) or transdermal therapy (patches delivering continuous 17-beta-estradiol, E2, 0.05 mg/day with sequential oral medroxyprogesterone acetate, MPA, 10 mg/day for 12 days/cycle). The groups had similar mean values and ranges of age, BMI and postmenopausal status. The blood samples were taken at baseline, and twice at 1 year before and after MPA administration. LDL particle size distribution was determined by gradient gel electrophoresis and LDL was isolated by sequential ultracentrifugation for compositional analyses. Concentrations of total LDL mass, LDL cholesterol and LDL protein decreased in the oral treatment group (p < 0.01, p < 0.001 and p < 0.01, respectively), whereas they remained unchanged during the transdermal therapy. Particle size of the major LDL peak remained unchanged during both transdermal and oral therapies. HDL cholesterol concentration decreased significantly in both treatment groups (p < 0.001 for both). Serum triglyceride and HDL cholesterol concentrations were the strongest determinants of LDL particle size ( r = -0.50 and r = 0.54, respectively, p < 0.001 for both). The cholesteryl esters and free cholesterol content of the LDL particles decreased in the oral treatment group (p < 0.05). Phospholipid content of LDL increased in both groups receiving either oral or transdermal therapy (p < 0.01 for both). In conclusion, oral administration of 17-beta-estradiol and norethisterone acetate caused a decrease in LDL mass by decreasing the number and cholesterol content of LDL particles. The concomitant decrease of HDL cholesterol by progestins may partly negate this beneficial effect of LDL lowering.

Administration, Cutaneous↗
PubMed2005

Determination of the transdermal bioavailability of a newly developed diclofenac sodium patch in comparison with a reference preparation.

Two different transdermal diclofenac (CAS 15307-86-5) formulations (Olfen Patch 140 mg diclofenac sodium as test preparation and 180 mg diclofenac epolamine plaster, equivalent to 140 mg diclofenac sodium, as reference preparation) were investigated in 24 healthy male and female volunteers in order to compare the transdermal bioavailability between both treatments following topical multiple dose administration. Subjects were applied 2 plasters of test and reference formulation at a dose interval of 12 h for 4 consecutive days. Test and reference preparation were administered in randomised sequence at a marked spot at the left upper arm under non-fasting conditions. For determination of diclofenac concentrations, pre-dose (trough) values were taken during steady-state build-up and during the period of switch-over between both preparations on days 1-3 and 5-7. Blood samples for pharmacokinetic profiling were taken on days 4 and 8 at pre-defined time points up to 24 h following drug administration (after the 7th resp. 15th dose). Treatments were not separated by a wash-out phase. Considering the short half-life of diclofenac, it was appropriate that a switch-over design was chosen without wash-out periods between treatments. Diclofenac plasma concentrations were determined by means of a validated LC-MS/MS method (limit of detection: 0.06 ng/ml; lower limit of quantification: 0.15 ng/ml). For the test preparation, maximum plasma concentrations of 3.36 ng/ml (C(max, 0-12)), 3.73 ng/ml (C(max, 12-24)) and 3.84 ng/ml (C(max, 0-24)) as well as areas under the plasma concentration-time curve (AUC) of 31.11 ng x h/ml (AUC(0-12), 34.83 ng x h/ml (AUC(12.24)) and 65.94 ng x h/ml (AUC(0-24)) were determined. For the reference preparation, these values were 1.55 ng/ml (C(max, 0-12)), 1.45 ng/ml (C(max, 12-24) and 1.57 ng/ml (C(max, 0-24)) as well as 13.28 ng x h/ml (AUC(0-12)), 12.68 ng x h/ml (AUC(12-24)) and 25.96 ng x h/ml (AUC(0-24)). For the test preparation, peak-to-trough fluctuations (% PTF) of 34.78% (% PTF(0-12)), 38.50% (% PTF(12-24)) and 43.68% (% PTF(0-24)) were observed. Corresponding values for the reference preparation were 35.82% (% PTF(0-12), 31.36% (% PTF(12-24)) and 40.55% (% PTF(0-24)). In order to evaluate comparable bioavailability of both preparations, 90% confidence intervals of the test/reference ratios were determined. Thereby, for all dose intervals considered and all AUC parameters calculated, the extent of diclofenac absorption from the test preparation markedly exceeds those values obtained for the reference preparation. Likewise, maximum plasma concentrations, as a measure for the rate of absorption, were higher after the test preparation. With respect to peak-to-trough fluctuation of plasma diclofenac levels, both plaster preparations were comparable for the morning dose interval 0-12 h as well as for the 0-24 h period.

Administration, Cutaneous↗
PubMed1995

Double blind trial of repeated treatment with transdermal nicotine for relapsed smokers.

OBJECTIVE: To assess the efficacy and safety of a repeat course of treatment with transdermal nicotine for cessation of smoking in a brief intervention setting. STUDY DESIGN: Randomised, double blind, placebo controlled trial with follow up for 26 weeks. SUBJECTS: 629 smokers who had unsuccessfully attempted to stop smoking by using active transdermal nicotine and brief behavioural counselling. Smokers were motivated to quit smoking for a second time and smoked > or = 15 cigarettes a day. INTERVENTIONS: Twelve weeks' treatment with active transdermal nicotine patches or placebo and brief counselling at monthly visits. MAIN OUTCOME MEASURE: Sustained smoking cessation for the 28 days before the visit at week 12 verified by expired carbon monoxide concentrations. RESULTS: At 12 weeks 21/315 (6.7%) subjects allocated to active treatment had stopped smoking compared with 6/314 (1.9%) allocated to placebo (absolute difference 4.7%; 95% confidence interval 1.6% to 7.9%; P = 0.003). At 26 weeks the rates were 20/315 (6.4%) and 8/314 (2.6%) (3.8%; 0.6% to 7.0%; P = 0.021). Difficulty in sleeping was reported by 43/179 (24.0%) on active treatment and 19/143 (13.3%) on placebo (P = 0.015). Severe reactions at the site of application were rare (6/322; 1.9%). CONCLUSIONS: Repeated treatment with transdermal nicotine together with brief counselling can improve the low success rates of smoking cessation in recently relapsed, moderate to heavy smokers. Questions remain about whether more intensive interventions or higher doses of nicotine could be more effective. The likelihood of severe reactions at the site of application with repeated treatment is low.

Administration, Cutaneous↗
PubMed2004

Transdermal estradiol improves bone density when used as single agent therapy for prostate cancer.

PURPOSE: Current androgen deprivation therapies for men with prostate cancer cause accelerated osteoporosis and a significant risk of osteoporotic fracture. We have recently shown that transdermal estradiol is an effective alternative for such patients. Here we report the impact of transdermal estradiol therapy on the bone mineral density of men with prostate cancer. MATERIALS AND METHODS: A total of 20 patients with newly diagnosed locally advanced or metastatic prostate cancer were treated with transdermal estradiol patches. Bone mineral density of the lumbar spine and the proximal femur was measured with dual-energy x-ray absorptiometry, and correlated with computerized tomography and isotope bone scan findings at 6-month intervals. RESULTS: In all measured regions bone mineral density increased with time. By 1 year mean bone mineral density +/- SEM had increased by 3.60% +/- 1.6% in the lumbar spine (p = 0.055), 2.19% +/- 1.03% in the femoral neck (p = 0.055), 3.76% +/- 1.35% in the Ward's region (p = 0.008) and 1.90% +/- 0.85% in the total hip (p = 0.031), respectively. Of 12 osteoporotic sites 4 had improvement based on World Health Organization grading. All other sites improved toward a better classification. CONCLUSIONS: Transdermal estradiol protects against bone loss in men with prostate cancer and may improve bone density in those at risk for osteoporotic fracture.

Administration, Cutaneous↗
PubMed1997

Postoperative analgesia using a low-dose, oral-transdermal clonidine combination: lack of clinical efficacy.

STUDY OBJECTIVE: To determine if a lower than previously reported oral-transdermal clonidine regimen could reduce postoperative morphine requirements without producing systemic side effects. DESIGN: Double-blind, randomized, placebo-controlled study. SETTING: University-affiliated hospital. PATIENTS: 29 healthy, ASA physical status I and II females undergoing elective abdominal hysterectomy. INTERVENTIONS: Patients received preoperative oral clonidine 4 to 5 mu/kg and a 7 cm2 transdermal clonidine patch (0.2 mg/24 hours) or a placebo tablet and patch. MEASUREMENTS AND MAIN RESULTS: Postoperative patient-controlled analgesia pumps provided morphine during the 48-hour study period. Morphine use, hemodynamic changes, and nonhemodynamic side effects were recorded. Additionally, visual analog pain scales (VAPS) and plasma concentrations of morphine and clonidine were measured. We found that low-dose clonidine had no potentiating effect on morphine analgesia. Postoperative morphine use, VAPS, and morphine plasma levels were similar between the control and clonidine-treated groups. Nevertheless, patients in the clonidine group experienced a significantly greater incidence of intraoperative and postoperative hypotension and bradycardia than did the control group. No differences were noted in the incidence of nonhemodynamic side effects. CONCLUSIONS: The low-dose oral-transdermal clonidine regimen evaluated failed to reduce postoperative morphine requirements, although patients who received clonidine were still at risk for developing hypotension.

Administration, Cutaneous↗
PubMed2005

Transdermal estradiol therapy for prostate cancer reduces thrombophilic activation and protects against thromboembolism.

PURPOSE: Oral estrogens were an effective treatment for prostate cancer but were abandoned because of an increased risk of cardiovascular toxicity and particularly thromboembolism. We have recently shown that transdermal estradiol produces an effective tumor response and negligible cardiovascular toxicity. Here we report the influence of transdermal estradiol therapy on the coagulation profile of men with advanced prostate cancer. MATERIALS AND METHODS: A total of 20 patients with newly diagnosed locally advanced or metastatic prostate cancer were treated using transdermal estradiol patches and the coagulation profile was assessed before and during 12 months therapy. Activation of coagulation was assessed by assaying the levels of activated factor VII (VIIa), activated factor XII (XIIa), prothrombin fragments 1 and 2 (F1 + 2), thrombin-antithrombin III (TAT III) complex and fibrinogen. Inhibition of the coagulation cascade was assayed by protein C, protein S and activated protein C resistance (APC-R). Fibrinolytic activity was determined by assaying tissue plasminogen activator (TPA) and plasminogen activation inhibitor type 1 (PAI-1). D-Dimer levels assessed both coagulation and fibrinolytic (thrombophilic) activity. Venous Duplex, color Doppler ultrasound and photoplethysmography were used to assess for thrombosis. RESULTS: Levels of VIIa and XIIa were unaffected by transdermal estradiol therapy. Although levels of TAT III were increased in some patients at 12 months, the increase was markedly less than that observed historically with equivalent doses of oral estrogens. Levels of the inhibitory and fibrinolytic factors including protein C, protein S, APC-R, TPA and PAI-1 remained stable. Reductions in F1+F2, fibrinogen and D-Dimer levels represented a normalization from increased levels to the physiological range. CONCLUSIONS: These results suggest that transdermal estradiol reduces thrombophilic activation in men with advanced prostate cancer, and protects against the risk of thrombosis.

Administration, Cutaneous↗